Lake-centred sedentary lifestyle of early Tibetan Plateau Indigenous populations at high elevation 4,400 years ago.

The onset of sedentism on the Tibetan Plateau is often presumed to be associated with the dispersal of agriculture or farmers from archaeological sites located in the low elevation margins of the plateau. Previous studies of the plateau assumed that all foragers were probably mobile, but few systematic excavations at forager sites have been conducted to inform us about their settlement patterns. Here we report the world's highest elevation sedentary way of living exhibited by the Mabu Co site at 4,446 metres above sea level, deep in the interior of the Tibetan Plateau 4,400-4,000 years ago. Our interdisciplinary study indicates that the site was occupied by Indigenous inhabitants of the plateau, representing the earliest known DNA evidence of foragers who predominantly harbour the southern plateau ancestry. The evidence shows that they had a sedentary lifestyle primarily supported by fishing at nearby lakes, supplemented by mammal and bird hunting, as well as small-scale exchanges of millet and rice crops.

Bronze Age cheese reveals human-Lactobacillus interactions over evolutionary history.

Despite the long history of consumption of fermented dairy, little is known about how the fermented microbes were utilized and evolved over human history. Here, by retrieving ancient DNA of Bronze Age kefir cheese (∼3,500 years ago) from the Xiaohe cemetery, we explored past human-microbial interactions. Although it was previously suggested that kefir was spread from the Northern Caucasus to Europe and other regions, we found an additional spreading route of kefir from Xinjiang to inland East Asia. Over evolutionary history, the East Asian strains gained multiple gene clusters with defensive roles against environmental stressors, which can be a result of the adaptation of Lactobacillus strains to various environmental niches and human selection. Overall, our results highlight the role of past human activities in shaping the evolution of human-related microbes, and such insights can, in turn, provide a better understanding of past human behaviors.

Genome-wide association study and KASP marker development for starch quality traits in wheat.

Starch is the main component of wheat (Triticum aestivum L.) flour, and its quality directly affects the processing quality of the final product. To investigate the genetic basis of starch, this study assessed the starch quality traits of 341 winter wheat varieties/lines grown in Emin and Qitai during the years 2019-2020 and 2020-2021. A genome-wide association study was conducted with the genotype data obtained from wheat 40K breeding chips using the mixed linear model. Wheat starch quality traits exhibited coefficients of variation ranging from 1.43% to 23.66% and broad-sense heritabilities between 0.37 and 0.87. All traits followed an approximately normal distribution, except for T. There were highly significant correlations among starch quality traits, with the strongest correlation observed between final viscosity (FV) and trough viscosity (TV) (r = 0.748), followed by peak viscosity and breakdown (BD) (r = 0.679). Thirty-four single-nucleotide polymorphism markers significantly and stably associated with starch quality traits were identified, clustering in 31 genetic loci. These included one locus for TV, six loci for BD, three loci for FV, two loci for peak time (PT), 12 loci for T, five loci for falling number, and two loci for damaged starch. One PT-related block of 410 kb was identified in the region of 596 Mb on chromosome 5A, where significant phenotypic differences were observed between different haplotypes. One Kompetitive allele-specific PCR (KASP) marker for T was developed on chromosome 7B, and two KASP markers for BD were developed on chromosome 7A. Four candidate genes possibly affecting BD during grain development were identified on chromosome 7A, including TraesCS7A02G225100.1, TraesCS7A02G225900.1, TraesCS7A02G226400.1, and TraesCS7A02G257100.1. The results have significant implications for utilizing marker-assisted selection in breeding to improve wheat starch quality.

Glycosylated AIE-active Red Light-triggered Photocage with Precisely Tumor Targeting Capability for Synergistic Type I Photodynamic Therapy and CPT Chemotherapy.

Photocaging is an emerging protocol for precisely manipulating spatial and temporal behaviors over biological activity. However, the red/near-infrared light-triggered photolysis process of current photocage is largely singlet oxygen (1O2)-dependent and lack of compatibility with other reactive oxygen species (ROS)-activated techniques, which has proven to be the major bottleneck in achieving efficient and precise treatment. Herein, we reported a lactosylated photocage BT-LRC by covalently incorporating camptothecin (CPT) into hybrid BODIPY-TPE fluorophore via the superoxide anion radical (O2-•)-cleavable thioketal bond for type I photodynamic therapy (PDT) and anticancer drug release. Amphiphilic BT-LRC could be self-assembled into aggregation-induced emission (AIE)-active nanoparticles (BT-LRCs) owing to the regulation of carbohydrate-carbohydrate interactions (CCIs) among neighboring lactose units in the nanoaggregates. BT-LRCs could simultaneously generate abundant O2-• through the aggregation modulated by lactose interactions, and DNA-damaging agent CPT was subsequently and effectively released. Notably, the type I PDT and CPT chemotherapy collaboratively amplified the therapeutic efficacy in HepG2 cells and tumor-bearing mice. Furthermore, the inherent AIE property of BT-LRCs endowed the photocaged prodrug with superior bioimaging capability, which provided a powerful tool for real-time tracking and finely tuning the PDT and photoactivated drug release behavior in tumor therapy.

Personnel Monitoring in Shipboard Surveillance Using Improved Multi-Object Detection and Tracking Algorithm.

Detecting and tracking personnel onboard is an important measure to prevent ships from being invaded by outsiders and ensure ship security. Ships are characterized by more cabins, numerous equipment, and dense personnel, so there are problems such as unpredictable personnel trajectories, frequent occlusions, and many small targets, which lead to the poor performance of existing multi-target-tracking algorithms on shipboard surveillance videos. This study conducts research in the context of onboard surveillance and proposes a multi-object detection and tracking algorithm for anti-intrusion on ships. First, this study designs the BR-YOLO network to provide high-quality object-detection results for the tracking algorithm. The shallow layers of its backbone network use the BiFormer module to capture dependencies between distant objects and reduce information loss. Second, the improved C2f module is used in the deep layer of BR-YOLO to introduce the RepGhost structure to achieve model lightweighting through reparameterization. Then, the Part OSNet network is proposed, which uses different pooling branches to focus on multi-scale features, including part-level features, thereby obtaining strong Re-ID feature representations and providing richer appearance information for personnel tracking. Finally, by integrating the appearance information for association matching, the tracking trajectory is generated in Tracking-By-Detection mode and validated on the self-constructed shipboard surveillance dataset. The experimental results show that the algorithm in this paper is effective in shipboard surveillance. Compared with the present mainstream algorithms, the MOTA, HOTP, and IDF1 are enhanced by about 10 percentage points, the MOTP is enhanced by about 7 percentage points, and IDs are also significantly reduced, which is of great practical significance for the prevention of intrusion by ship personnel.

[Therapeutic effect of Lingze Tablets on benign prostatic hyperplasia in rats: An exploration based on the VEGFA/TNF/IL-6 signaling pathway].

OBJECTIVE: To explore the mechanism of Lingze Tablets (LZT) acting on BPH in rats based on the VEGFA/TNF/IL-6 signaling pathway. METHODS: We equally randomized 30 SPF SD male rats into five groups, normal control, BPH model control, low-dose LZT, medium-dose LZT and high-dose LZT, and established a BPH model in the latter four groups by induction with non-castrate testosterone propionate. After the modeling, we treated the rats in the normal and model groups by intragastrical administration of physiological saline, and those in the latter three groups with low-, medium-, and high-dose LZT respectively, all for 28 successive days. Then we collected the prostate tissue from the animals for observation of the changes in the prostatic indexes and histomorphology, detected the expressions of the proteins related to the VEGFA/TNF/IL-6 signaling pathway, and compared the data obtained among different groups. RESULTS: Compared with the normal controls, the rats in the model control group showed significant prostatic hyperplasia, markedly increased prostatic index (ï¼»0.84 ± 0.01ï¼½ g, P<0.05), thickness of the prostatic epithelia and infiltration of the luminal area, and dramatically up-regulated protein expressions of VEGFA (0.60 ± 0.02, P< 0.05), TNF (0.76 ± 0.02, P< 0.05) and IL-6 (0.64 ± 0.02, P< 0.05). In comparison with the model controls, the rats in the low-, medium- and high-dose LZT groups exhibited significantly decreased prostatic indexes (ï¼»0.76 ± 0.02ï¼½ g, ï¼»0.58 ± 0.02ï¼½ g and ï¼»0.52 0.01ï¼½ g, all P< 0.05), improved prostatic histomorphology, and down-regulated expressions of VEGFA (0.45 ± 0.01, 0.35 ± 0.01 and 0.31 ± 0.02, all P< 0.05), TNF (0.45 ± 0.01, 0.33 ± 0.01 and 0.27 ± 0.01, all P< 0.01) and IL-6 (0.44 ± 0.01, 0.36 ± 0.01 and 0.30 ± 0.01, all P< 0.01) in a dose-dependent manner. CONCLUSION: LZT produces therapeutic effect on BPH by negatively regulating the VEGFA/TNF/IL-6 signaling pathway, reducing the expression levels of VEGFA, TNF and IL-6 proteins, and regulating cell proliferation, apoptosis and inflammatory response.

Advancing Superconductivity with Interface Engineering.

The development of superconducting materials has attracted significant attention not only for their improved performance, such as high transition temperature (TC), but also for the exploration of their underlying physical mechanisms. Recently, considerable efforts have been focused on interfaces of materials, a distinct category capable of inducing superconductivity at non-superconducting material interfaces or augmenting the TC at the interface between a superconducting material and a non-superconducting material. Here, two distinct types of interfaces along with their unique characteristics are reviewed: interfacial superconductivity and interface-enhanced superconductivity, with a focus on the crucial factors and potential mechanisms responsible for enhancing superconducting performance. A series of materials systems is discussed, encompassing both historical developments and recent progress from the perspectives of technical innovations and the exploration of new material classes. The overarching goal is to illuminate pathways toward achieving high TC, expanding the potential of superconducting parameters across interfaces, and propelling superconductivity research toward practical, high-temperature applications.

Nanobody-based strategy for rapid and accurate pathogen detection: A case of COVID-19 testing.

Antibody pairs-based immunoassay platforms served as essential and effective tools in the field of pathogen detection. However, the cumbersome preparation and limited detection sensitivity of antibody pairs challenge in establishment of a highly sensitive detection platform. In this study, using COVID-19 testing as a case, we utilized readily accessible nanobodies as detection antibodies and further proposed an accurate design concept with a more scientific and efficient screening strategy to obtain ultrasensitive antibody pairs. We employed nanobodies capable of binding different antigenic epitopes of the nucleocapsid (NP) or receptor-binding domain (RBD) antigens sandwich as substitutes for monoclonal antibodies (mAbs) sandwich in fast detection formats and utilized time-resolved fluorescence (TRF) microspheres as the signal probe. Consequently, we developed a multi-epitope nanobody sandwich-based fluorescence lateral flow immunoassay (FLFA) strip. Our results suggest that the NP antigen had a detection limit of 12.01pg/mL, while the RBD antigen had a limit of 6.51 pg/mL using our FLFA strip. Based on double mAb sandwiches, the values presented herein demonstrated 4 to 32-fold enhancements in sensitivity, and 32 to 256-fold enhancements compared to commercially available antigen lateral flow assay kits. Furthermore, we demonstrated the excellent characteristics of the proposed test strip, including its specificity, stability, accuracy, and repeatability, which underscores its the prospective utility. Indeed, these findings indicate that our established screening strategy along with the multi-epitope nanobody sandwich mode provides an optimized strategy in the field of pathogen detection.

VolcanoSV enables accurate and robust structural variant calling in diploid genomes from single-molecule long read sequencing.

Structural variants (SVs) significantly contribute to human genome diversity and play a crucial role in precision medicine. Although advancements in single-molecule long-read sequencing offer a groundbreaking resource for SV detection, identifying SV breakpoints and sequences accurately and robustly remains challenging. We introduce VolcanoSV, an innovative hybrid SV detection pipeline that utilizes both a reference genome and local de novo assembly to generate a phased diploid assembly. VolcanoSV uses phased SNPs and unique k-mer similarity analysis, enabling precise haplotype-resolved SV discovery. VolcanoSV is adept at constructing comprehensive genetic maps encompassing SNPs, small indels, and all types of SVs, making it well-suited for human genomics studies. Our extensive experiments demonstrate that VolcanoSV surpasses state-of-the-art assembly-based tools in the detection of insertion and deletion SVs, exhibiting superior recall, precision, F1 scores, and genotype accuracy across a diverse range of datasets, including low-coverage (10x) datasets. VolcanoSV outperforms assembly-based tools in the identification of complex SVs, including translocations, duplications, and inversions, in both simulated and real cancer data. Moreover, VolcanoSV is robust to various evaluation parameters and accurately identifies breakpoints and SV sequences.

Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis.

OBJECTIVE: Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. METHODS: We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. RESULTS: Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions. CONCLUSION: The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

Leisure Activity, Childhood Starvation, and Risk of Incident Diabetes in Older Adults: Evidence from a Chinese Nationwide Cohort Study.

OBJECTIVE: This study explores the impact of leisure activity and the association between childhood starvation and the risk of diabetes in older Chinese adults. DESIGN: Prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study (CLHLS), a nationwide cohort study in China. SETTING AND PARTICIPANTS: A total of 4637 older adults aged ≥65 years, all with documented diabetes history, experiences of childhood starvation, and participation in leisure activities were recruited. METHODS: Childhood starvation exposure was assessed via self-reported responses from a structured questionnaire. The leisure activities were measured by 9 distinctive components and categorized into 3 distinct categories: productive activity, recreational activity, and sedentary activity. Diabetes status was determined by self-reported, physician-diagnosed cases during the follow-up period. Nonparametric survival models were employed for analysis. RESULTS: Over an average follow-up period of 4.3 years, 215 of 4637 participants (4.6%) reported a confirmed diagnosis of diabetes. Nonparametric survival models showed that those reporting childhood starvation had a higher risk of late-life diabetes [hazard ratio (HR) 1.72, 95% CI 1.21-2.44]. Engaging in productive activity (HR 0.90, 95% CI 0.83-0.99) and recreational activity (HR 0.88, 95% CI 0.77-1.00) was linked with a reduced risk of late-life diabetes. Sedentary activity did not show a significant effect. Further analysis highlighted the interactions effects of leisure activities on diabetes risk across different demographic and historical exposure subgroups. CONCLUSIONS AND IMPLICATIONS: Engaging in productive and recreational leisure activities was inversely associated with the risk of diabetes in older adults who experienced childhood starvation. Promoting such activities could be beneficial in mitigating long-term diabetes risk related to early-life nutritional deficiencies.

A Multifunctional Nanocatalytic Metal-Organic Framework as a Ferroptosis Amplifier for Mild Hyperthermia Photothermal Therapy.

Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy.

Zinc-doped C4N3/BiOBr S-scheme heterostructured hollow spheres for efficient photocatalytic degradation of tetracycline.

Photocatalytic degradation of organic pollutants in water is of great significance to the sustainable development of the environment, but encounters limited efficiency when a single compound is used. Thus, there have been enormous efforts to find novel photocatalytic heterostructured composites with high performance. In this work, a novel S-scheme heterostructure is constructed with BiOBr and Zn2+ doped C4N3 (Zn-C4N3) by a solvothermal method for efficient photodegradation of tetracycline (TC), a residual antibiotic difficult to be removed from the aquatic environment. Thanks to Zn2+-doping induced improvement in chemical affinity between Zn-C4N3 and BiOBr, well-formed Zn-C4N3/BiOBr heterostructured hollow spheres are formed. This structure can efficiently suppress fast recombination of photogenerated electron-hole pairs to enhance the photocatalytic activity of BiOBr dramatically. At a room temperature of 25 °C and neutral pH 7, the catalyst can degrade a significant portion of TC pollutants within 30 min under visible light. Also, the Zn-C4N3/BiOBr heterostructure displays good stability after recycling experiments. Free radical capture experiments and ESR tests show that ˙O2- is the main active substance for photocatalytic degradation of TC. This study provides new insights for constructing heterostructures with an intimate interface between the two phases for photocatalytic applications.

The Role of Traditional Chinese Medicines in the Treatment of Osteoporosis.

Osteoporosis (OP) represents a substantial public health issue and is associated with increasing rates of morbidity and mortality. It is characterized by reduced bone mineral density, deterioration of bone tissue quality, disruption of the microarchitecture of bones, and compromised bone strength. These changes may be attributed to the following factors: intercellular communication between osteoblasts and osteoclasts; imbalanced bone remodeling; imbalances between osteogenesis and adipogenesis; imbalances in hormonal regulation; angiogenesis; chronic inflammation; oxidative stress; and intestinal microbiota imbalances. Treating a single aspect of the disease is insufficient to address its multifaceted nature. In recent decades, traditional Chinese medicine (TCM) has shown great potential in the treatment of OP, and the therapeutic effects of Chinese patent drugs and Chinese medicinal herbs have been scientifically proven. TCMs, which contain multiple components, can target the diverse pathogeneses of OP through a multitargeted approach. Herbs such as XLGB, JTG, GSB, Yinyanghuo, Gusuibu, Buguzhi, and Nvzhenzi are among the TCMs that can be used to treat OP and have demonstrated promising effects in this context. They exert their therapeutic effects by targeting various pathways involved in bone metabolism. These TCMs balance the activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells), and they exhibit anti-inflammatory, immunomodulatory, anti-oxidative, and estrogen-like functions. These multifaceted mechanisms underlie the efficacy of these herbs in the management and treatment of OP. Herein, we examine the efficacy of various Chinese herbs and Chinese patent drugs in treating OP by reviewing previous clinical trials and basic experiments, and we examine the potential mechanism of these therapies to provide evidence regarding the use of TCM for treating OP.

Primary Robotic Versus Conventional Laparoscopic Roux-en-Y Gastric Bypass in Morbidly Obese Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Robotic Roux-en-Y gastric bypass (RRYGB) and conventional laparoscopic Roux-en-Y gastric bypass (LRYGB) are commonly performed as primary bariatric procedures. The aim of this article was to assess the role of RRYGB in patients undergoing primary bariatric procedures. METHODS: All of the qualified studies were selected from the PubMed, Embase, and Web of Science databases, etc. We mainly compared the outcomes and safety between RRYGB and LRYGB. The outcomes evaluation included surgical effect and surgical safety. RESULT: In total, 35 studies containing 426,463 patients were selected. The mortalities of patients adopting these 2 bariatric procedures were similar (RRYGB: 59/28,023, 0.21%; LRYGB: 612/397,945, 0.15%). We found no significant difference between RRYGB and LRYGB in the incidence of postoperative complications (30-day: OR=1.06, P =0.18; 1-y: OR=1.06, P =0.92). The incidence of 30-day readmission after the operation was higher in RRYGB patients (OR=1.24, P =0.003). However, we found that the RRYGB group had a lower incidence of anastomotic stricture 1 year after the operation when compared with LRYGB (OR=0.35, P =0.0004). The 1-year %EBMIL of these 2 groups was similar (78.53% vs. 76.02%). There was no significant difference in length of hospital stay (LOS) (WMD=-0.03d, P =0.59), conversion rate (OR=0.84, P =0.75), or anastomotic leak (OR=1.00, P =0.99) between these 2 groups. The mean hospital charges were higher in the RRYGB group ($11234.75 vs. $9468.58). CONCLUSION: This systematic review and meta-analysis showed no significant advantage of RRYGB in surgical effect or reduction of intraoperative complications. RRYGB may reduce the incidence of some postoperative long-term complications. The mean hospital charges of RRYGB were higher.

Comparisons of procyanidins with different low polymerization degrees on prevention of lipid metabolism in high-fat diet/streptozotocin-induced diabetic mice.

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.

Unlocking Efficiency: Minimizing Energy Loss in Electrocatalysts for Water Splitting.

Catalysts play a crucial role in water electrolysis by reducing the energy barriers for hydrogen and oxygen evolution reactions (HER and OER). Research aims to enhance the intrinsic activities of potential catalysts through material selection, microstructure design, and various engineering techniques. However, the energy consumption of catalysts has often been overlooked due to the intricate interplay among catalyst microstructure, dimensionality, catalyst-electrolyte-gas dynamics, surface chemistry, electron transport within electrodes, and electron transfer among electrode components. Efficient catalyst development for high-current-density applications is essential to meet the increasing demand for green hydrogen. This involves transforming catalysts with high intrinsic activities into electrodes capable of sustaining high current densities. This review focuses on current improvement strategies of mass exchange, charge transfer, and reducing electrode resistance to decrease energy consumption. It aims to bridge the gap between laboratory-developed, highly efficient catalysts and industrial applications regarding catalyst structural design, surface chemistry, and catalyst-electrode interplay, outlining the development roadmap of hierarchically structured electrode-based water electrolysis for minimizing energy loss in electrocatalysts for water splitting.

Profiling of m6A methylation in porcine intramuscular adipocytes and unravelling PHKG1 represses porcine intramuscular lipid deposition in an m6A-dependent manner.

Intramuscular fat (IMF) content is mainly determined by intramuscular preadipocyte adipogenesis. Epigenetic modifications are known to have a regulatory effect on IMF. As N6-methyladenosine (m6A) is the most abundant epigenetic modification in eukaryotic RNAs. In the present study, we used m6A methylation and RNA sequencing (seq) to identify the m6A-modified RNAs associated with the adipogenic differentiation of intramuscular preadipocytes. Among them, the expression and m6A level of phosphorylase kinase subunit G1 (PHKG1) were found to be significantly changed during adipogenesis. Further studies revealed that knockdown of the methylase METTL3 decreased the m6A methylation of PHKG1 and led to a reduction in PHKG1. Moreover, knockdown of PHKG1 promoted adipogenic differentiation by upregulating the expression of adipogenic genes. In addition, we found that the IMF content in the longissimus thoracis (LT) of Bamei (BM) pigs was greater than that in Large White (LW) pigs, whereas the m6A and PHKG1 expression levels were lower in BM pigs. These findings indicate that the m6A level and expression of PHKG1 were significantly correlated with IMF content and meat quality. In conclusion, this study sheds light on the mechanism by which m6A modification regulates IMF deposition.

Comparison analysis of bioactive metabolites in soybean, pea, mung bean, and common beans: reveal the potential variations of their antioxidant property.

This study showed the significantly differences of basic nutrients and metabolite compounds in nine types of beans involved in soybean, mung bean, pea, and common beans. The metabolomics results showed that serval metabolites such as histidine, proline, 3-alanine, and myricetin which could be used to identify different beans. The random forest model showed that amino acid and fatty acid could be used as special indexes to distinguish different types of beans in practice. The different expressed metabolites among different types of beans were involved in various pathways including alanine, aspartate and glutamate metabolism, arginine and proline metabolism, and purine metabolism. The antioxidant activity was significantly different among different types of beans, and the contents of amino acid, coumarin, and polyphenol contributed the antioxidant activities of beans. Together, these results will provide a comprehensive understanding of metabolites in different types of beans and theoretical guideline for the future application of beans.

Ancient genomes revealed the complex human interactions of the ancient western Tibetans.

The western Tibetan Plateau is the crossroad between the Tibetan Plateau, Central Asia, and South Asia, and it is a potential human migration pathway connecting these regions. However, the population history of the western Tibetan Plateau remains largely unexplored due to the lack of ancient genomes covering a long-time interval from this area. Here, we reported genome-wide data of 65 individuals dated to 3,500-300 years before present (BP) in the Ngari prefecture. The ancient western Tibetan Plateau populations share the majority of their genetic components with the southern Tibetan Plateau populations and have maintained genetic continuity since 3,500 BP while maintaining interactions with populations within and outside the Tibetan Plateau. Within the Tibetan Plateau, the ancient western Tibetan Plateau populations were influenced by the additional expansion from the south to the southwest plateau before 1,800 BP. Outside the Tibetan Plateau, the western Tibetan Plateau populations interacted with both South and Central Asian populations at least 2,000 years ago, and the South Asian-related genetic influence, despite being very limited, was from the Indus Valley Civilization (IVC) migrants in Central Asia instead of the IVC populations from the Indus Valley. In light of the new genetic data, our study revealed the complex population interconnections across and within the Tibetan Plateau.