Milk fat synthesis is tightly regulated by hormones and growth factors. Leptin is a versatile peptide hormone that exerts pleiotropic effects on metabolic pathways. In this study, we evaluated the expression and function of leptin and its long form receptor OB-Rb in dairy cow mammary tissues from different physiological stages and in cultured mammary epithelial cells. The results showed that the expression of leptin and OB-Rb were significantly higher in the mammary tissues of lactating cows as compared with dry cows, suggesting that they are related to milk component synthesis. In cultured dairy cow mammary epithelial cells, leptin treatment significantly increased OB-Rb expression and intracellular triacylglycerol content. Transcriptome analysis identified the difference in gene expression between leptin treated cells and control cells, and 317 differentially expressed genes were identified. Gene ontology and pathway mapping showed that lipid metabolism-related gene expression increased and signal transduction pathway-related genes were the most significantly enriched. Mechanistic studies showed that leptin stimulation enhanced sterol regulatory element-binding protein 1 expression via activating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway, which in turn up-regulated the expression of genes related to milk fat synthesis. Moreover, we found that fatty acid synthesis precursors, acetate and β-hydroxybutyrate, could positively regulate the expression of leptin and OB-Rb in bovine mammary epithelial cells, thereby potentially increasing milk fat synthesis. Our study provided novel evidence in the regulation of leptin on milk fat production in mammary glands of dairy cows, as well as experimental basis for artificial regulation of milk fat

This research communication screened and identified differentiated expressed genes in bovine mammary epithelial cells (BMECs) upon prolactin (PRL) stimulation. PRL of 5 μg/ml increased β-casein synthesis in BMECs with milk protein synthesis capacity. RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs). A total of 375 DEGs (165 up-regulated and 210 down-regulated) were identified between PRL-stimulated group and the control group. Gene ontology enrichment analysis showed that the up-regulated genes were primarily associated with cell functions, metabolic processes, and biological regulatory processes. Pathway enrichment analysis showed that the up-regulated genes were mainly enriched in JAK-STAT, Rap1, Ras and Notch signaling pathways, which are widely involved in cell proliferation, differentiation and milk component synthesis. This study provides an initial understanding of the changes in gene expression in BMECs with PRL-stimulation, as determined by RNA-seq transcriptomic analysis, thereby enhancing our knowledge of the molecular regulation of lactation metabolism.

Gentiana straminea Maxim. (Gentianaceae) is an important traditional Tibetan herb that is mainly distributed on the Qinghai-Tibetan Plateau. Despite its agricultural and pharmacological importance, there remains a paucity of microsatellite markers, particularly expressed sequence tag-simple sequence repeat (EST-SSR) markers, available for this local endemic species. In this study, based on previous Illumina transcriptome data of G. straminea, a total of 96 EST-SSR markers were initially designed and tested. Thirty-two of 96 loci (33.33%) were successfully amplified and verified for validation. Among them, 10 were polymorphic and had clear bands. The polymorphism information content values were 0.09–0.799, the number of alleles per locus ranged from 3 to 14, and the levels of observed and expected heterozygosity were 0.078–0.722 and 0.238–0.884, respectively, which suggested a high level of information. Moreover, cross-amplification was successful for 10 loci in two other related species, Gentiana macrophylla Pallas and Gentiana dahurica Fischer. These EST-SSR markers provide a valuable tool for investigating the genetic diversity related to quantitative traits and population genetic studies on G. straminea and related species in sect. Cruciata Gaudin.

Accurately predicting neurosyphilis prior to a lumbar puncture (LP) is critical for the prompt management of neurosyphilis. However, a valid and reliable model for this purpose is still lacking. This study aimed to develop a nomogram for the accurate identification of neurosyphilis in patients with syphilis. The training cohort included 9,504 syphilis patients who underwent initial neurosyphilis evaluation between 2009 and 2020, while the validation cohort comprised 526 patients whose data were prospectively collected from January 2021 to September 2021. Neurosyphilis was observed in 35.8% (3,400/9,504) of the training cohort and 37.6% (198/526) of the validation cohort. The nomogram incorporated factors such as age, male gender, neurological and psychiatric symptoms, serum RPR, a mucous plaque of the larynx and nose, a history of other STD infections, and co-diabetes. The model exhibited good performance with concordance indexes of 0.84 (95% CI, 0.83–0.85) and 0.82 (95% CI, 0.78–0.86) in the training and validation cohorts, respectively, along with well-fitted calibration curves. This study developed a precise nomogram to predict neurosyphilis risk in syphilis patients, with potential implications for early detection prior to an LP.

This paper proposes a low-divergence method to generate inhomogeneous and anisotropic turbulence. Based on the idea of correlation reconstruction, the proposed method uses the Cholesky decomposition matrix to re-establish turbulence correlation functions. This is in contrast with the time-consuming procedure used in conventional methods to solve eigenvalues and eigenvectors in each location required by coordinate transformation, thereby reducing the computational complexity and improving the efficiency of synthetic turbulence generation. The proposed method is based on the classical spectrum-based method that is widely used to generate homogeneous and isotropic turbulence. By adjusting the generation strategy of specific random vectors, inhomogeneous and anisotropic turbulence with a relatively low divergence level can be obtained in practice, with almost no additional computational burden. Two versions of the proposed method are presented: the inverter and shifter versions. Both the versions are highly efficient, easy to implement, and compatible with high-performance computing. This method is also suitable for providing high-quality initial or boundary conditions for scale-resolving turbulence simulations with large grid numbers (such as direct numerical simulations or large eddy simulations); it can be rapidly implemented using various open-source computational fluid dynamics codes or common commercial software.

Over the years, numerous observational studies have substantiated that various dietary choices have opposing effects on CVD. However, the causal effect has not yet been established. Thus, we conducted a Mendelian randomisation (MR) analysis to reveal the causal impact of dietary habits on CVD. Genetic variants strongly associated with 20 dietary habits were selected from publicly available genome-wide association studies conducted on the UK Biobank cohort (n 449 210). Summary-level data on CVD were obtained from different consortia (n 159 836–977 323). The inverse-variance weighted method (IVW) was the primary outcome, while MR-Egger, weighted median and MR Pleiotropy RESidual Sum and Outlier were used to assess heterogeneity and pleiotropy. We found compelling evidence of a protective causal effect of genetic predisposition towards cheese consumption on myocardial infarction (IVW OR = 0·67; 95 % CI = 0·544, 0·826; P = 1·784 × 10−4) and heart failure (IVW OR = 0·646; 95 % CI = 0·513, 0·814; P = 2·135 × 10−4). Poultry intake was found to be a detrimental factor for hypertension (IVW OR = 4·306; 95 % CI = 2·158, 8·589; P = 3·416 × 10−5), while dried fruit intake was protective against hypertension (IVW OR = 0·473; 95 % CI = 0·348, 0·642; P = 1·683 × 10−6). Importantly, no evidence of pleiotropy was detected. MR estimates provide robust evidence for a causal relationship between genetic predisposition to 20 dietary habits and CVD risk, suggesting that well-planned diets may help prevent and reduce the risk of CVD.

The study aimed to explore the relationships of skeletal muscle mass with disease severity in metabolic-associated fatty liver disease (MAFLD) patients with different methods. Consecutive subjects undergoing bioelectrical impedance analysis were included. The steatosis grade and liver fibrosis were evaluated by MRI-derived proton density fat fraction and two-dimensional shear wave elastography. The appendicular skeletal muscle mass (ASM) was adjusted by height2 (ASM/H2), weight (ASM/W) and BMI (ASM/BMI). Overall, 2223 subjects (50·5 %, MAFLD; 46·9 %, male) were included, with the mean age 37·4 ± 10·6 years. In multivariate logistic regression analysis, the subjects with the lowest quartile (Q1) of ASM/W or ASM/BMI had higher risk ratios for MAFLD (OR (95 % CI) in male: 2·57 (1·35, 4·89), 2·11(1·22, 3·64); in female: 4·85 (2·33, 10·01), 4·81 (2·52, 9·16), all P < 0·05, all for Q1 v. Q4). The MAFLD patients with lower quartiles of ASM/W had the higher risk OR for insulin resistance (IR), both in male and female (2·14 (1·16, 3·97), 4·26 (1·29, 14·02) for Q4 v. Q1, both P < 0·05). While the significant OR were not observed when ASM/H2 and ASM/BMI were used. There were significant dose-dependent associations between decreased ASM/W as well as ASM/BMI and moderate–severe steatosis (2·85(1·54, 5·29), 1·90(1·09, 3·31), both P < 0·05) in male MAFLD patients. In conclusion, ASM/W is superior to ASM/H2 and ASM/BMI in predicting the degree of MAFLD. A lower ASM/W is associated with IR and moderate–severe steatosis in non-elderly male MAFLD.

This research communication investigated the role and the underlying mechanism of sn-1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6) in acetate-induced mTORC1 signaling activation and milk fat synthesis in dairy cow mammary epithelial cells. The data showed AGPAT6 knockdown significantly decreased acetate-induced phosphorylation of mTORC1 signaling molecules and intracellular triacylglycerol (TAG) content, whereas this inhibition effect was reversed after the addition of 16:0,18:1 phosphatidic acid (PA), suggesting that AGPAT6 could generate PA in response to acetate simulation, that in turn activates mTORC1 signaling. PPARγ is the upstream regulator of AGPAT6 upon acetate stimulation. Luciferase assay with clones containing various deletions and mutation in AGPAT6 promoter showed that there is a RXRα binding sequence located at −96 bp of AGPAT6 promoter. Acetate stimulation significantly increased the interaction between PPARγ and AGPAT6 via this RXRα binding site. Taken together, our data indicated that AGPAT6 could activate mTORC1 signaling by producing PA during acetate-induced milk fat synthesis, and PPARγ acts as a transcription factor to mediate the effect of acetate on AGPAT6 via RXRα.

Listeriosis is a rare but serious foodborne disease caused by Listeria monocytogenes. This matched case–control study (1:1 ratio) aimed to identify the risk factors associated with food consumption and food-handling habits for the occurrence of sporadic listeriosis in Beijing, China. Cases were defined as patients from whom Listeria was isolated, in addition to the presence of symptoms, including fever, bacteraemia, sepsis and other clinical manifestations corresponding to listeriosis, which were reported via the Beijing Foodborne Disease Surveillance System. Basic patient information and possible risk factors associated with food consumption and food-handling habits were collected through face-to-face interviews. One hundred and six cases were enrolled from 1 January 2018 to 31 December 2020, including 52 perinatal cases and 54 non-perinatal cases. In the non-perinatal group, the consumption of Chinese cold dishes increased the risk of infection by 3.43-fold (95% confidence interval 1.27–9.25, χ2 = 5.92, P = 0.02). In the perinatal group, the risk of infection reduced by 95.2% when raw and cooked foods were well-separated (χ2 = 5.11, P = 0.02). These findings provide important scientific evidence for preventing infection by L. monocytogenes and improving the dissemination of advice regarding food safety for vulnerable populations.

Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.

The present study evaluated effects of dietary supplementation with tryptophan (Trp) on muscle growth, protein synthesis and antioxidant capacity in hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. Fish were fed six different diets containing 2·6 (control), 3·1, 3·7, 4·2, 4·7 and 5·6 g Trp/kg diet for 56 d, respectively. Results showed that dietary Trp significantly (1) improved muscle protein content, fibre density and frequency of fibre diameter; (2) up-regulated the mRNA levels of PCNA, myf5, MyoD1, MyoG, MRF4, IGF-I, IGF-II, IGF-IR, PIK3Ca, TOR, 4EBP1 and S6K1; (3) increased phosphorylation levels of AKT, TOR and S6K1; (4) decreased contents of MDA and PC, and increased activities of CAT, GST, GR, ASA and AHR; (5) up-regulated mRNA levels of CuZnSOD, CAT, GST, GPx, GCLC and Nrf2, and decreased Keap1 mRNA level; (6) increased nuclear Nrf2 protein level and the intranuclear antioxidant response element-binding ability, and reduced Keap1 protein level. These results indicated that dietary Trp improved muscle growth, protein synthesis as well as antioxidant capacity, which might be partly related to myogenic regulatory factors, IGF/PIK3Ca/AKT/TOR and Keap1/Nrf2 signalling pathways. Finally, based on the quadratic regression analysis of muscle protein and MDA contents, the optimal Trp requirements of hybrid catfish (21·82–39·64 g) were estimated to be 3·94 and 3·93 g Trp/kg diet (9·57 and 9·54 g/kg of dietary protein), respectively.

The staining procedure is critical for investigating intra- and extra-cellular ultrastructure of microorganisms by transmission electron microscopy (TEM). Here, we propose a new ultra-low lead staining (ULLS) technique for preparing the ultrathin sections for TEM analysis. Sections of Enterobacter sp. (bacteria), Aspergillus niger (filamentous fungi), Rhodotorula mucilaginosa (fungi), and Chlamydomonas reinhardtii (microalgae) were tested. Compared with the sections prepared by the typical double-staining technique, ULLS-based sections showed evident advantages: (i) the staining process only required the addition of Pb(NO3)2; (ii) the Pb level during incubation was set as low as 1 mg/L, which had negligible toxicity to most microbial cells; (iii) the Pb cations were added during microbial culture, which avoided complicated sample preparation as in typical double staining. Taking C. reinhardtii as an example, the ULLS technique allowed fine investigation of microbial ultrastructure, e.g., starch granule, mitochondrion, Golgi apparatus, vacuole, and vesicle. Meanwhile, the physiological processes of the cells such as cell lysis and exocytosis were successfully captured, with relatively high contrast. This study hence shows a bright future on preparation of the high-quality ultrathin sections of microbial cells by the ULLS technique.

Power scaling based on traditional ytterbium-doped fibers (YDFs) is limited by optical nonlinear effects and transverse mode instability (TMI) in high-power fiber lasers. Here, we propose a novel long tapered fiber with a constant cladding and tapered core (CCTC) along its axis direction. The tapered-core region of the fiber is designed to enhance the stimulated Raman scattering (SRS) threshold and suppress higher-order mode resonance in the laser cavity. The CCTC YDF was fabricated successfully with a modified chemical vapor deposition (MCVD) method combined with solution doping technology, which has a cladding diameter of 400 μm and a varying core with a diameter of ~24 μm at both ends and ~31 μm in the middle. To test the performance of the CCTC fiber during high-power operation, an all-fiber laser oscillator based on a CCTC YDF was investigated experimentally. As a result, a maximum output power of 3.42 kW was achieved with an optical-to-optical efficiency of 55.2%, although the TMI effect was observed at an output power of ~3.12 kW. The measured beam quality (M2 factor) was ~1.7, and no sign of the Raman component was observed in the spectrum. We believe that CCTC YDF has great potential to simultaneously mitigate the SRS and TMI effects, and further power scaling is promising by optimizing the structure of the YDF.