Under the coupling effect of node position deviation, joint clearance and wear factors, the complex landing gear retraction mechanism suffers from low kinematic accuracy, slow retraction performance and shortened reliable life. Addressing these issues, a time-dependent reliability analysis and optimisation design method for the kinematic accuracy of the retraction mechanism is proposed, considering the uncertainty of node position deviation, initial clearance, and dynamic multi-joint wear. Initially, a wear prediction model and a dynamic model of the retraction mechanism considering node position deviation and joint clearance are established to analyse their influence on retraction accuracy and joint wear depth. Subsequent retraction testing under various working conditions is conducted to ascertain the critical failure condition and validate the simulation model. The time-dependent kinematic accuracy reliability model, accounting for the dynamic evolution of wear clearance, is then established to assess reliability variation with retraction cycles. Finally, the reliability optimisation design focusing on hole-axis matching accuracy aims to strike a balance between accuracy cost and reliability, thereby enhancing performance and prolonging operational life.

Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive and prevalent breast cancer subtype that lacks targeted therapies. This study aims to investigate whether the niclosamide derivative HJC0152 can modulate tumor-derived PD-L1 expression and enhance the effectiveness of anti-PD-1 immunotherapy in treating TNBC. Methods/Study Population: Niclosamide derivative HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human TNBC cell line (MDA-MB-231) was treated with HJC0152, and activation of the STAT3 signaling pathway was evaluated using Western blotting. RNA-Seq was employed to analyze the expression of protein-coding genes, particularly those related to immune response. To study therapeutic potential in vivo, TNBC mouse models will be treated with single agent treatments as well as a combination therapy of HJC0152 and anti-PD-1. Tumor volume and mass will be measured over time to determine growth inhibition. Results/Anticipated Results: Preliminary studies indicate that HJC0152 exhibits enhanced solubility compared to Niclosamide, along with high anticancer potency both in vitro and in vivo. HJC0152 was found to effectively inhibit the activation of phosphorylated STAT3 (p-STAT3) in MDA-MB-231 cells, a key signaling pathway associated with cancer progression and immune evasion. RNA-Seq analysis of HJC0152-treated MDA-MB-231 cells revealed a decrease in PD-L1 expression, an essential immune checkpoint protein involved in tumor immune suppression. These findings suggest that HJC0152 is a promising immune modulator that may enhance the efficacy of immune checkpoint blockade therapy for TNBC. Discussion/Significance of Impact: This study explores an innovative immunotherapy for TNBC using the Niclosamide derivative HJC0152, which inhibits STAT3 signaling and downregulates PD-L1. Results from this study will provide a foundation for HJC0152’s inclusion in clinical trials and potentially offer a new and promising therapeutic option for TNBC treatment.

This study investigates the effects of fat emulsion-based early parenteral nutrition in patients following hemihepatectomy, addressing a critical gap in clinical knowledge regarding parenteral nutrition after hemihepatectomy. We retrospectively analysed clinical data from 274 patients who received non-fat emulsion-based parenteral nutrition (non-fatty nutrition group) and 297 patients who received fat emulsion-based parenteral nutrition (fatty nutrition group) after hemihepatectomy. Fat emulsion-based early parenteral nutrition significantly reduced levels of post-operative aspartate aminotransferase, total bilirubin and direct bilirubin, while minor decreases in red blood cell and platelet counts were observed in the fatty nutrition group. Importantly, fat emulsion-based early parenteral nutrition shortened lengths of post-operative hospital stay and fasting duration, but did not affect the incidence of short-term post-operative complications. Subgroup analyses revealed that the supplement of n-3 fish oil emulsions was significantly associated with a reduced inflammatory response and risk of post-operative infections. These findings indicate that fat emulsion-based early parenteral nutrition enhances short-term post-operative recovery in patients undergoing hemihepatectomy.

This study demonstrates a kilowatt-level, spectrum-programmable, multi-wavelength fiber laser (MWFL) with wavelength, interval and intensity tunability. The central wavelength tuning range is 1060–1095 nm and the tunable number is controllable from 1 to 5. The wavelength interval can be tuned from 6 to 32 nm and the intensity of each channel can be adjusted independently. Maximum output power up to approximately 1100 W has been achieved by master oscillator power amplifier structures. We also investigate the wavelength evolution experimentally considering the difference of gain competition, which may give a primary reference for kW-level high-power MWFL spectral manipulation. To the best of our knowledge, this is the highest output power ever reported for a programmable MWFL. Benefiting from its high power and flexible spectral manipulability, the proposed MWFL has great potential in versatile applications such as nonlinear frequency conversion and spectroscopy.

A high-energy picosecond 355 nm ultraviolet (UV) laser operating at 100 Hz was demonstrated. A 352 mJ, 69 ps, 1064 nm laser at 100 Hz was realized firstly by cascaded regenerative, laser diode end-pumped single-pass and side-pumped main amplifiers. The stimulated Raman scattering-based beam shaping technique, thermally induced birefringence compensation and 4f spatial filter-image relaying systems were used to maintain a relatively homogeneous beam intensity distribution during the amplification process. By using lithium triborate crystals for second- and third-harmonic generation (THG), a 172 mJ, approximately 56 ps, 355 nm UV laser was achieved with a THG conversion efficiency of 49%. To the best of our knowledge, it is the highest pulse energy of a picosecond 355 nm UV laser so far. The beam quality factor ${M}^2$ and pulse energy stability were ${M}_x^2$=3.92, ${M}_y^2$=3.71 and root mean square of 1.48%@3 hours. This laser system could play significant roles in applications including photoconductive switch excitation, laser drilling and laser micro-fabrication.

Oncomelania hupensis (O. hupensis), the sole intermediate host of Schistosoma japonicum, greatly influence the prevalence and distribution of schistosomiasis japonica. The distribution area of O. hupensis has remained extensive for numerous years. This study aimed to establish a valid agent-based model of snail density and further explore the environmental conditions suitable for snail breeding. A marshland with O. hupensis was selected as a study site in Dongting Lake Region, and snail surveys were monthly conducted from 2007 to 2016. Combined with the data from historical literature, an agent-based model of snail density was constructed in NetLogo 6.2.0 and validated with the collected survey data. BehaviorSpace was used to identify the optimal ranges of soil temperature, pH, soil water content, and vegetation coverage for snail growth, development and reproduction. An agent-based model of snail density was constructed and showed a strong agreement with the monthly average snail density from the field surveys. As soil temperature increased, the snail density initially rose before declining, reaching its peak at around 21°C. There were similar variation patterns for other environmental factors. The findings from the model suggested that the optimum ranges of soil temperature, pH, soil water content and vegetation coverage were 19°C to 23 °C, 6.4 to 7.6, 42% to 75%, and 70% to 93%, respectively. A valid agent-based model of snail density was constructed, providing more objective information about the optimum ranges of environmental factors for snail growth, development and reproduction.

Iodine (I) is a trace element with health and environmental significance. Iodate (IO3-), iodide (I-) and organic iodine (org-I) are the major species of iodine that exist in the environment. Dissimilatory IO3--reducing bacteria reduce IO3- to I- directly under anoxic conditions via their IO3- reductases that include periplasmic iodate reductase IdrABP1P2, extracellular DMSO reductase DmsEFAB and metal reductase MtrCAB. IdrAB and DmsEFAB reduce IO3- to hypoiodous acid (HIO) and H2O2. The reaction intermediate HIO is proposed to be disproportionated abiotically into I- and IO3- at a ratio of 2:1. The H2O2 is reduced to H2O by IdrP1P2 and MtrCAB as a detoxification mechanism. Additionally, dissimilatory Fe(III)- and sulfate-reducing bacteria reduce IO3- to I- directly via their IO3- reductases and indirectly via the reduction products Fe(II) and sulfide in the presence of Fe(III) and sulfate, respectively. I--oxidizing bacteria oxidize I- to molecular iodine (I2) directly under oxic conditions via their extracellular multicopper iodide oxidases IoxAC. In addition to I2, a variety of org-I compounds are also produced by the I--oxidizing bacteria during I- oxidation. Furthermore, ammonia-oxidizing bacteria oxidize I- to IO3- directly under oxic conditions, probably via their intracellular ammonia-oxidizing enzymes. Many bacteria produce extracellular reactive oxygen species that can oxidize I- to triiodide (I3-). Bacteria also accumulate I- during which I- is oxidized to HIO by their extracellular vanadium iodoperoxidases. The HIO is then transported into the bacterial cells. Finally, bacteria methylate I- to org-I CH3I, probably via their methyltransferases. Thus, bacteria play crucial and versatile roles in the global biogeochemical cycling of iodine via IO3- reduction, I- oxidation and accumulation and org-I formation.

Accurate dynamic model is essential for the model-based control of robotic systems. However, on the one hand, the nonlinearity of the friction is seldom treated in robot dynamics. On the other hand, few of the previous studies reasonably balance the calculation time-consuming and the quality for the excitation trajectory optimization. To address these challenges, this article gives a Lie-theory-based dynamic modeling scheme of multi-degree-of-freedom (DoF) serial robots involving nonlinear friction and excitation trajectory optimization. First, we introduce two coefficients to describe the Stribeck characteristics of Coulomb and static friction and consider the dependency of friction on load torque, so as to propose an improved Stribeck friction model. Whereafter, the improved friction model is simplified in a no-load scenario, a novel nonlinear dynamic model is linearized to capture the features of viscous friction across the entire velocity range. Additionally, a new optimization algorithm of excitation trajectories is presented considering the benefits of three different optimization criteria to design the optimal excitation trajectory. On the basis of the above, we retrieve a feasible dynamic parameter set of serial robots through the hybrid least square algorithm. Finally, our research is supported by simulation and experimental analyses of different combinations on the seven-DoF Franka Emika robot. The results show that the proposed friction has better accuracy performance, and the modified optimization algorithm can reduce the overall time required for the optimization process while maintaining the quality of the identification results.

China is still among the 30 high-burden tuberculosis (TB) countries in the world. Few studies have described the spatial epidemiological characteristics of pulmonary TB (PTB) in Jiangsu Province. The registered incidence data of PTB patients in 95 counties of Jiangsu Province from 2011 to 2021 were collected from the Tuberculosis Management Information System. Three-dimensional spatial trends, spatial autocorrelation, and spatial–temporal scan analysis were conducted to explore the spatial clustering pattern of PTB. From 2011 to 2021, a total of 347,495 newly diagnosed PTB cases were registered. The registered incidence rate of PTB decreased from 49.78/100,000 in 2011 to 26.49/100,000 in 2021, exhibiting a steady downward trend (χ2 = 414.22, P < 0.001). The average annual registered incidence rate of PTB was higher in the central and northern regions. Moran’s I indices of the registered incidence of PTB were all >0 (P< 0.05) except in 2016, indicating a positive spatial correlation overall. Local autocorrelation analysis showed that ‘high–high’ clusters were mainly distributed in northern Jiangsu, and ‘low–low’ clusters were mainly concentrated in southern Jiangsu. The results of this study assist in identifying settings and locations of high TB risk and inform policy-making for PTB control and prevention.

Previous studies revealed that consuming spicy food reduced mortality from CVD and lowered stroke risk. However, no studies reported the relationship between spicy food consumption, stroke types and dose–response. This study aimed to further explore the association between the frequency of spicy food intake and the risk of stroke in a large prospective cohort study. In this study, 50 174 participants aged 30–79 years were recruited. Spicy food consumption data were collected via a baseline survey questionnaire. Outcomes were incidence of any stroke, ischaemic stroke (IS) and haemorrhagic stroke (HS). Multivariable-adjusted Cox proportional hazard models estimated the association between the consumption of spicy food and incident stroke. Restricted cubic spline analysis was used to examine the dose–response relationship. During the median 10·7-year follow-up, 3967 strokes were recorded, including 3494 IS and 516 HS. Compared with those who never/rarely consumed spicy food, those who consumed spicy food monthly, 1–2 d/week and 3–5 d/week had hazard ratio (HR) of 0·914 (95 % CI 0·841, 0·995), 0·869 (95 % CI 0·758, 0·995) and 0·826 (95 % CI 0·714, 0·956) for overall stroke, respectively. For IS, the corresponding HR) were 0·909 (95 % CI 0·832, 0·994), 0·831 (95 % CI 0·718, 0·962) and 0·813 (95 % CI 0·696, 0·951), respectively. This protective effect showed a U-shaped dose–response relationship. For obese participants, consuming spicy food ≥ 3 d/week was negatively associated with the risk of IS. We found the consumption of spicy food was negatively associated with the risk of IS and had a U-shaped dose–response relationship with risk of IS. Individuals who consumed spicy food 3–5 d/week had a significantly lowest risk of IS.

Breathe is a student-led literary and arts magazine whose goal is to provide a platform for creative expression about mental health issues and promote mental wellness among trainee healthcare professionals using student-submitted art and written pieces. Select pieces were published to improve readers’ understanding of and self-reflection on mental health. Common themes among the submissions include life outside of healthcare, imposter syndrome and coping with stress. This novel project had high satisfaction reported by 87.5% of surveyed readers. We advocate for improved mental health awareness and increased use of artistic expression as a coping strategy against stressors in healthcare education worldwide.

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

Limonite is mainly derived from weathering of Fe sulfide, iron-bearing carbonate, or silicate minerals. The weathering of Fe sulfide or carbonate minerals to yield limonite from the Tongling mineralization cluster has been studied extensively. Knowledge of the mineralogical and geochemical characteristics of the limonite from weathering of Fe-bearing silicate minerals is still incomplete, however. To address this, black limonite containing ilvaite (a silicate mineral) found in Yeshan iron deposit, Tongling, China, was studied using mineralogical and chemical analysis. The mineralogical characteristics indicated that Mn goethite was present as nano-granular (<15 nm) or acicular (50–100 nm long, ~10 nm wide, i.e. high length/width ratio) crystals with low crystallinity. Groutite, ramsdellite, and pyrolusite were identified in the limonite as ~5 nm nanoparticles, and coated on the goethite surface. Amorphous Fe-Mn phases and silica were highly developed in the limonite studied. Ilvaite crystals showed idiomorphic granular morphology and were replaced by Fe-Mn oxides/hydroxides; pyrite was also present as inclusions within the ilvaite and the ilvaite structural formula calculated was Ca1.04(Fe1.57Mn0.31Mg0.04)(Fe1.09Al0.01)[Si1.95O]O(OH). According to the relatively high CuO and ZnO values and the low Al2O3 value in the black limonite, the negative correlations between (Fe2O3+MnO) and (CuO+ZnO+BaO), (Fe2O3+MnO) and Al2O3, high Mn and Si contents, and the characteristics of the textural relationships and compositions between the black limonite and ilvaite, a semi-enclosed environment with acidic to weakly alkaline conditions was deduced; ilvaite was found to be responsible for the formation and enrichment of limonite.

Raman spectroscopic analysis was performed on columbite-(Mn) samples from a variety of previously studied rare-element pegmatites in Xinjiang, China, including the Jing'erquan No. 1 spodumene-subtype, Dakalasu No. 1 beryl–columbite-subtype and Kalu'an spodumene-subtype pegmatites, to quantify the relationship between the degree of metamictisation of columbite and Raman spectra. For all of the analysed columbites-(Mn), the position (p) and the full width at half maximum (FWHM) of the strongest band, A1g vibration mode related to the Nb/Ta–O bond, in the Raman spectra have a negative correlation. Combined with previously determined U–Pb isotopic data and major–minor-element data for the columbites-(Mn), the degree of metamictisation was quantified using the alpha-decay dose (D) and displacement per atom (dpa), both of which were corrected for effects caused by annealing. The results demonstrate that the columbite-(Mn) from Jing'erquan and Kalu'an are very crystalline, whereas those from Dakalasu are transitional between crystalline and amorphous stages. The main factor influencing the key parameters, i.e. band position and FWHM, of the strongest Raman band of columbite-(Mn) is metamictisation caused by radiation damage, whereas composition and crystal orientation have limited influence. A set of equations are established to quantify the degree of metamictisation of columbite using the band position and the full width at half maximum: FWHM = 8.309 × ln(aD) + 30.11 (R2 = 0.9861); p = –5.187 × ln(aD) + 867.09 (R2 = 0.966); FWHM = 8.1453 × ln(adpa) + 48.425 (R2 = 0.9822); and p = –5.078 × ln(adpa) + 855.67 (R2 = 0.9594).

The associations of red/processed meat consumption and cancer-related health outcomes have been well discussed. The umbrella review aimed to summarise the associations of red/processed meat consumption and various non-cancer-related outcomes in humans. We systematically searched the systematic reviews and meta-analyses of associations between red/processed meat intake and health outcomes from PubMed, Embase, Web of Science and the Cochrane Library databases. The umbrella review has been registered in PROSPERO (CRD 42021218568). A total of 40 meta-analyses were included. High consumption of red meat, particularly processed meat, was associated with a higher risk of all-cause mortality, CVD and metabolic outcomes. Dose–response analysis revealed that an additional 100 g/d red meat intake was positively associated with a 17 % increased risk of type 2 diabetes mellitus (T2DM), 15 % increased risk of CHD, 14 % of hypertension and 12 % of stroke. The highest dose–response/50 g increase in processed meat consumption at 95 % confident levels was 1·37, 95 % CI (1·22, 1·55) for T2DM, 1·27, 95 % CI (1·09, 1·49) for CHD, 1·17, 95 % CI (1·02, 1·34) for stroke, 1·15, 95 % CI (1·11, 1·19) for all-cause mortality and 1·08, 95 % CI (1·02, 1·14) for heart failure. In addition, red/processed meat intake was associated with several other health-related outcomes. Red and processed meat consumption seems to be more harmful than beneficial to human health in this umbrella review. It is necessary to take the impacts of red/processed meat consumption on non-cancer-related outcomes into consideration when developing new dietary guidelines, which will be of great public health importance. However, more additional randomised controlled trials are warranted to clarify the causality.