We prove lower bounds on the density of regular minimal cones of dimension less than seven provided the complements of the cones are topologically nontrivial.

Tuberculosis (TB) remains a significant public health concern in China. Using data from the Global Burden of Disease (GBD) study 2021, we analyzed trends in age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and disability-adjusted life years (DALYs) for TB from 1990 to 2021. Over this period, HIV-negative TB showed a marked decline in ASIR (AAPC = −2.34%, 95% CI: −2.39, −2.28) and ASMR (AAPC = −0.56%, 95% CI: −0.62, −0.59). Specifically, drug-susceptible TB (DS-TB) showed reductions in both ASIR and ASMR, while multidrug-resistant TB (MDR-TB) showed slight decreases. Conversely, extensively drug-resistant TB (XDR-TB) exhibited upward trends in both ASIR and ASMR. TB co-infected with HIV (HIV-DS-TB, HIV-MDR-TB, HIV-XDR-TB) showed increasing trends in recent years. The analysis also found an inverse correlation between ASIRs and ASMRs for HIV-negative TB and the Socio-Demographic Index (SDI). Projections from 2022 to 2035 suggest continued increases in ASIR and ASMR for XDR-TB, HIV-DS-TB, HIV-MDR-TB, and HIV-XDR-TB. The rising burden of XDR-TB and HIV-TB co-infections presents ongoing challenges for TB control in China. Targeted prevention and control strategies are urgently needed to mitigate this burden and further reduce TB-related morbidity and mortality.

The extracellular matrices, such as the haemolymph, in insects are at the centre of most physiological processes and are protected from oxidative stress by the extracellular antioxidant enzymes. In this study, we identified two secreted superoxide dismutase genes (PxSOD3 and PxSOD5) and investigated the oxidative stress induced by chlorpyrifos (CPF) in the aquatic insect Protohermes xanthodes (Megaloptera: Corydalidae). PxSOD3 and PxSOD5 contain the signal peptides at the N-terminus. Structure analysis revealed that PxSOD3 and PxSOD5 contain the conserved CuZn-SOD domain, which is mainly composed of β-sheets and has conserved copper and zinc binding sites. Both PxSOD3 and PxSOD5 are predicted to be soluble proteins located in the extracellular space. After exposure to different concentrations of sublethal CPF, MDA content in P. xanthodes larvae were increased in a dose-dependent manner; SOD and CAT activities were also higher in CPF-treated groups than that in the no CPF control, indicating that sublethal CPF induces oxidative stress in P. xanthodes larvae. Furthermore, PxSOD3 and PxSOD5 expression levels and haemolymph SOD activity in the larvae were downregulated by sublethal CPF at different concentrations. Our results suggest that the PxSOD3 and PxSOD5 are putative extracellular antioxidant enzymes that may play a role in maintaining the oxidative balance in the extracellular space. Sublethal CPF may induce oxidative stress in the extracellular space of P. xanthodes by reducing the gene expression and catalytic activity of extracellular SODs.

Previous studies claimed that the non-monotonic effects of wettability came mainly from the heterogeneity of geometries or flow conditions on multiphase displacements in porous media. For macroscopic homogeneous porous media, without permeability contrast or obvious preferential flow pathways, most pore-scale evidence showed a monotonic trend of the wettability effect. However, this work reports transitions from monotonic to non-monotonic wettability effects when the dimension of the model system rises from two-dimensional (2-D) to three-dimensional (3-D), validated by both the network modelling and the microfluidic experiments. The mechanisms linking the pore-scale events to macroscopic displacement patterns have been analysed through direct simulations. For 2-D porous media, the monotonic effect of wettability comes from the consistent transition pattern for the full range of capillary numbers $Ca$, where the capillary fingering mode transitions to the compact displacement mode as the contact angle $\theta$ decreases. Yet, it is indicated that the 3-D porous geometries, even though homogeneous without permeability contrast or obvious preferential flow pathways, introduce a different $Ca$–$\theta$ phase diagram with new pore-scale events, such as the coupling of capillary fingering with snap-off during strong drainage, and frequent snap-off events during strong imbibition. These events depend strongly on geometric confinements and capillary numbers, leading to the non-monotonicity of wettability effects. Our findings provide new insights into the multiphase displacement dependent on wettability in various natural porous media and offer design principles for engineering artificial porous media to achieve desired immiscible displacement behaviours.

An actively controllable cascaded proton acceleration driven by a separate 0.8 picosecond (ps) laser is demonstrated in proof-of-principle experiments. MeV protons, initially driven by a femtosecond laser, are further accelerated and focused into a dot structure by an electromagnetic pulse (EMP) on the solenoid, which can be tuned into a ring structure by increasing the ps laser energy. An electrodynamics model is carried out to explain the experimental results and show that the dot-structured proton beam is formed when the outer part of the incident proton beam is optimally focused by the EMP force on the solenoid; otherwise, it is overfocused into a ring structure by a larger EMP. Such a separately controlled mechanism allows precise tuning of the proton beam structures for various applications, such as edge-enhanced proton radiography, proton therapy and pre-injection in traditional accelerators.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovial membrane, leading to cartilage destruction and bone erosion. Due to the complex pathogenesis of RA and the limitations of current therapies, increasing research attention has been directed towards novel strategies targeting fibroblast-like synoviocytes (FLS), which are key cellular components of the hyperplastic pannus. Recent studies have highlighted the pivotal role of FLS in the initiation and progression of RA, driven by their tumour-like transformation and the secretion of pro-inflammatory mediators, including cytokines, chemokines and matrix metalloproteinases. The aggressive phenotype of RA-FLS is marked by excessive proliferation, resistance to apoptosis, and enhanced migratory and invasive capacities. Consequently, FLS-targeted therapies represent a promising avenue for the development of next-generation RA treatments. The efficacy of such strategies – particularly those aimed at modulating FLS signalling pathways – has been demonstrated in both preclinical and clinical settings, underscoring their therapeutic potential. This review provides an updated overview of the pathogenic mechanisms and functional roles of FLS in RA, with a focus on critical signalling pathways under investigation, including Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), Notch and interleukin-1 receptor-associated kinase 4 (IRAK4). In addition, we discuss the emerging understanding of FLS-subset-specific contributions to immunometabolism and explore how computational biology is shaping novel targeted therapeutic strategies. A deeper understanding of the molecular and functional heterogeneity of FLS may pave the way for more effective and precise therapeutic interventions in RA.

Oasis communities across Central Asia were key to the emergence and maintenance of the ancient Silk Roads that spanned Eurasia from the late second century BC, yet our understanding of early interaction networks in this region is limited. Multi-isotopic analysis of human teeth from the Zaghunluq Cemetery, southern Xinjiang (sixth century BC to first century AD) now suggests that oasis communities established intricate exchange networks, forming strong ties with other nearby oases and mountain pastoralists and weak ties, facilitated through in migration, with more distant regions. These diverse connections, the authors argue, made possible cultural exchange across the challenging geography of eastern Central Asia.

This study presents a novel investigation into the vortex dynamics of flow around a near-wall rectangular cylinder based on direct numerical simulation at $Re=1000$, marking the first in-depth exploration of these phenomena. By varying aspect ratios ($L/D = 5$, $10$, $15$) and gap ratios ($G/D = 0.1$, $0.3$, $0.9$), the study reveals the vortex dynamics influenced by the near-wall effect, considering the incoming laminar boundary layer flow. Both $L/D$ and $G/D$ significantly influence vortex dynamics, leading to behaviours not observed in previous bluff body flows. As $G/D$ increases, the streamwise scale of the upper leading edge (ULE) recirculation grows, delaying flow reattachment. At smaller $G/D$, lower leading edge (LLE) recirculation is suppressed, with upper Kelvin–Helmholtz vortices merging to form the ULE vortex, followed by instability, differing from conventional flow dynamics. Larger $G/D$ promotes the formation of an LLE shear layer. An intriguing finding at $L/D = 5$ and $G/D = 0.1$ is the backward flow of fluid from the downstream region to the upper side of the cylinder. At $G/D = 0.3$, double-trailing-edge vortices emerge for larger $L/D$, with two distinct flow behaviours associated with two interactions between gap flow and wall recirculation. These interactions lead to different multiple flow separations. For $G/D = 0.9$, the secondary vortex (SV) from the plate wall induces the formation of a tertiary vortex from the lower side of the cylinder. Double-SVs are observed at $L/D = 5$. Frequency locking is observed in most cases, but is suppressed at $L/D = 10$ and $G/D = 0.9$, where competing shedding modes lead to two distinct evolutions of the SV.

Ice shelves affect the stability of ice sheets by supporting the mass balance of ice upstream of the grounding line. Marine ice, formed from supercooled water freezing at the base of ice shelves, contributes to mass gain and affects ice dynamics. Direct measurements of marine ice thickness are rare due to the challenges of borehole drilling. Here we assume hydrostatic equilibrium to estimate marine ice distribution beneath the Amery Ice Shelf (AIS) using meteoric ice-thickness data obtained from radio-echo sounding collected during the Chinese National Antarctic Research Expedition between 2015 and 2019. This is the first mapping of marine ice beneath the AIS in nearly 20 years. Our new estimates of marine ice along two longitudinal bands beneath the northwest AIS are spatially consistent with earlier work but thicker. We also find a marine ice layer exceeding 30 m of thickness in the central ice shelf and patchy refreezing downstream of the grounding line. Thickness differences from prior results may indicate time-variation in basal melting and freezing patterns driven by polynya activity and coastal water intrusions masses under the ice shelf, highlighting that those changes in ice–ocean interaction are impacting ice-shelf stability.

Manned lunar landers must ensure astronaut safety while enhancing payload capacity. Due to traditional landers being weak in high-impact energy absorb and heavy payload capacity, a Starship-type manned lunar lander is proposed in this paper. Firstly, a comprehensive analysis was conducted on the traditional cantilever beam cushioning mechanism for manned lander. Subsequently, a 26-ton manned lander and its landing mechanism were designed, and a rigid-flexible coupling dynamic analysis was performed on the compression process of the primary and auxiliary legs. Secondly, the landing performance of the proposed Starship-type manned lunar lander was compared with the traditional 14-ton manned lander in multiple landing conditions. The results indicate that under normal conditions, the largest acceleration of the proposed 26-ton Starship-type manned lander decreases more than 13.1%. It enables a significant increase in payload capacity while mitigating impact loads under various landing conditions.

We report an anomalous capillary phenomenon that reverses typical capillary trapping via nanoparticle suspension and leads to a counterintuitive self-removal of non-aqueous fluid from dead-end structures under weakly hydrophilic conditions. Fluid interfacial energy drives the trapped liquid out by multiscale surfaces: the nanoscopic structure formed by nanoparticle adsorption transfers the molecular-level adsorption film to hydrodynamic film by capillary condensation, and maintains its robust connectivity, then the capillary pressure gradient in the dead-end structures drives trapped fluid motion out of the pore continuously. The developed mathematical models agree well with the measured evolution dynamics of the released fluid. This reversing capillary trapping phenomenon via nanoparticle suspension can be a general event in a random porous medium and could dramatically increase displacement efficiency. Our findings have implications for manipulating capillary pressure gradient direction via nanoparticle suspensions to trap or release the trapped fluid from complex geometries, especially for site-specific delivery, self-cleaning, or self-recover systems.

Objectives/Goals: We investigate how the gut microbiome protects against arsenic toxicity, showing antibiotic perturbation increases toxicity and causes interindividual susceptibility to a sepsis-like disease state in mice. Here, we aim to understand how baseline microbiomes from various mouse vendors impact these outcomes and characterize the observed disease. Methods/Study Population: We developed a novel mouse model where mice are exposed to an antibiotic (cefoperazone) for 2 days, followed by co-exposure to the antibiotic and 100 ppm arsenate. So far, we have evaluated C57BL/6N mice from MSU’s in-house colony, Taconic Biosciences (TAC), and Jackson Labs (JAX), along with C57BL/6J mice from JAX. To determine if the baseline microbiome drives inter-vivarium differences, we established in-house breeding colonies of TAC- and JAX-origin mice at MSU. This allowed us to assess whether, when housed under identical conditions, these mice still show differences in mortality based on their original microbiomes. To characterize the arsenic-induced sepsis-like disease, we performed blood biochemistry assays to quantify the white blood cell populations, and sepsis biomarkers used in clinical settings. Results/Anticipated Results: We observed differences in survival rates between genetically identical mice from MSU (45%), TAC (30%), and JAX (2.5%) in our model. From this, we characterized the baseline composition of the gut microbiomes of these mice and found they were significantly different from each other. We are still awaiting results from our in-house TAC and JAX experiments but expect them to have similar gut microbiome compositions to those directly purchased from TAC and JAX and respond similarly. In our blood biochemistry analysis, we found sick mice presented with low WBC counts and notable biomarkers indicative of liver, heart, and kidney distress. We also anticipate that 16S sequencing results of cecal contents will further support findings by providing evidence of a bacterial infection in the ceca of sick mice. Discussion/Significance of Impact: Collectively, our work demonstrates that antibiotic perturbation of the gut microbiome induces an inter-individual and inter-vivarium susceptibility to an arsenic-induced sepsis-like disease state. This work highlights the importance of considering antibiotic use in the risk assessment of arsenic to better protect the health of those exposed.

This study elucidated the impacts of coenzyme Q10 (COQ10) supplementation in a high-fat diet (HFD) on growth, lipid metabolism and mitochondrial function in spotted seabass (Lateolabrax maculatus). Totally five diets were formulated: a diet with normal fat content (11 % lipid, NFD), a HFD (17 % lipid) and three additional diets by supplementing 5, 20 or 80 mg/kg of COQ10 to the HFD. After an 8-week culture period, samples were collected and analysed. The results demonstrated that COQ10 inclusion prevented the HFD-induced deterioration of growth performance and feed utilisation. COQ10 alleviated the deposition of saturated fatty acids following HFD intake and promoted the assimilation of n-3 and n-6 PUFA. Moreover, COQ10 administration inhibited the surge in serum transaminase activity and reduced hepatic lipid content following HFD ingestion, which was consistent with the results of oil red O staining. In addition, HFD feeding led to reduced hepatic citrate synthase and succinate dehydrogenase activities and decreased ATP content. Notably, COQ10 administration improved these indices and up-regulated the expression of mitochondrial biogenesis-related genes (pgc-1α, pgc-1β, nrf-1, tfam) and autophagy-related genes (pink1, mul1, atg5). In summary, supplementing 20–80 mg/kg of COQ10 in the HFD promoted growth performance, alleviated hepatic fat accumulation and enhanced liver mitochondrial function in spotted seabass.

This paper provides an overview of the current status of ultrafast and ultra-intense lasers with peak powers exceeding 100 TW and examines the research activities in high-energy-density physics within China. Currently, 10 high-intensity lasers with powers over 100 TW are operational, and about 10 additional lasers are being constructed at various institutes and universities. These facilities operate either independently or are combined with one another, thereby offering substantial support for both Chinese and international research and development efforts in high-energy-density physics.

The prevalence of co-morbid anxiety and depression varies greatly between research studies, making it difficult to understand and estimate the magnitude of this problem. This systematic review and meta-analysis aim to provide up-to-date information on the global prevalence of co-morbid anxiety and depression in pregnant and postpartum women and to further investigate the sources of heterogeneity. Systematic searches of eight electronic databases were conducted for original studies published from inception to December 10, 2024. We selected studies that directly reported prevalence data on co-morbid anxiety and depression during the perinatal periods. We extracted data from published study reports and calculated the pooled prevalence of symptoms of co-morbid anxiety and depression. There are 122 articles involving 560,736 women from 43 different countries included in this review. The global prevalence of co-morbid anxiety and depression during the perinatal period was about 9% (95%CI 8%–10%), with approximately 9% (95%CI 8%–11%) in pregnant women and 8% (95%CI 7%–10%) in postpartum women. Prevalence varied significantly by the assessment time points, study country, study design, and the assessment tool used for anxiety and depression, while prevalence was not dependent on publication year, country income level, and COVID-19 context. No publication bias was observed for this prevalence rate. These findings suggest that approximately 1 in 10 women experience co-morbid anxiety and depression during pregnancy and postpartum. Targeted action is needed to reduce this burden.

This study investigates the spatial distribution of inertial particles in turbulent Taylor–Couette flow. Direct numerical simulations are performed using a one-way coupled Eulerian–Lagrangian approach, with a fixed inner-wall Reynolds number of 2500 for the carrier flow, while the particle Stokes number ($St$) varies from 0.034 to 1 for the dispersed phase. We first examine the issue of preferential concentration of particles near the outer-wall region. Employing two-dimensional Voronoï analysis, we observe a pronounced particle clustering with increasing $St$, particularly evident in regions of low fluid velocity. Additionally, we investigate the concentration balance equation, inspired by the work of Johnson et al. (J. Fluid Mech., vol. 883, 2020, A27), to examine the particle radial distribution. We discern the predominant sources of influence, namely biased sampling, turbophoresis and centrifugal effects. Across all cases, centrifugal force emerges as the primary driver, causing particle migration toward the outer wall. Biased sampling predominantly affects smaller inertial particles, driving them toward the inner wall due to sampling within Taylor rolls with inward radial velocity. Conversely, turbophoresis primarily impacts larger inertial particles, inducing migration towards both walls where turbulent intensity is weaker compared with the bulk. With the revealed physics, our work provides a basis for predicting and controlling particle movement and distribution in industrial applications.