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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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The interest in nanocomposite films incorporating edible ingredients and active nanoparticles has surged due to their potential to enhance food quality and prolong shelf-life. This research focused on developing innovative exopolysaccharides (EPS)/potato starch (PS) nanocomposite films integrated with g-C 3 N 4 and AgNO 3 . Extensive analysis was conducted to assess the microstructure, physical attributes and antimicrobial properties of these films. Fourier transform infrared (FT-IR) analysis revealed electrostatic and hydrogen bonding interactions within the film components. X-ray diffraction (XRD) and X-ray photoelectron spectrometer (XPS) data indicated a high level of compatibility among EPS, PS, g-C 3 N 4 , and AgNO 3 , with no new absorption peaks or characteristic signals of C 3 N 4 and Ag appearing in the nanocomposite films patterns. The thickness, water solubility and water vapor permeability (WVP) of the EPS-PS-C 3 N 4 -Ag nanocomposite film increased due to the addition of g-C 3 N 4 , reached 0.31 ± 0.03 nm, 36.61 ± 1.76 % and 1.42 ± 0.34 × 10 -10  g -1  s -1  Pa -1 , respectively. While transparency, swelling degree, and oxygen permeability (OP) significantly decreased, reached 26.18 ± 2.38 %, 63.01 ± 2.51 % and 41.98 ± 1.28 %, respectively. Scanning electron microscopy (SEM) and atomic force microscope (AFM) images depicted an augmented roughness and porosity on the film surface upon integration of g-C 3 N 4 and AgNO 3 . Moreover, the EPS-PS-C 3 N 4 -Ag nanocomposite film displayed enhanced mechanical strength due to the presence of g-C 3 N 4 . The melting temperature (Tm) of EPS-PS-C 3 N 4 -Ag nanocomposite film was 313.3 °C, the removal rates of DPPH and ABTS was 66.11 ± 2.87 % and 45.09 ± 1.23 % respectively. Significant inhibition of microbial growth was observed in film containing g-C 3 N 4 and AgNO 3 , which demonstrated no toxicity towards NIH-33 cells, suggesting their potential application as promising active packaging material for food preservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cold exposure (CE) therapy is an innovative and cost-efficient cancer treatment that activates brown adipose tissue to compete for glucose uptake, leading to metabolic starvation in tumors. Exploring the combined antitumor mechanisms of CE and traditional therapies (such as nanocatalysis) is exciting and promising. In this study, a platelet membrane biomimetic single-atom nanozyme (SAEs) nanodrug (PFB) carrying bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide (BPTES) is developed for use in cancer CE therapy. Owing to the platelet membrane modification, PFB can effectively target tumors. Upon entering cancer cells, the dual starvation effect induced by CE treatment and BPTES can significantly diminish intracellular glucose and ATP levels, resulting in a substantial reduction in cellular (glutathione) GSH, which can enhance the cytotoxic efficacy of reactive oxygen species generated by SAEs. This strategy not only boosts ROS production in tumors, but also strengthens immune responses, particularly by increasing memory T-cell abundance and suppressing distant tumor growth and tumor metastasis. Compared with SAEs therapy alone, this combined approach offers superior benefits for tumor immunotherapy. This study achieves a combination of CE and nanomedicines for the first time, providing new ideas for future nanomedicine combination therapy modalities., (© 2024 Wiley‐VCH GmbH.)

Radiotherapy, despite its precision and non-invasiveness, often fails due to the resistance of cancer stem cells (CSCs), which are characterized by high self-renewal capabilities and superior DNA repair mechanisms. These cells can evade RT and lead to tumor recurrence and metastasis. To address this challenge, a novel delivery system named PB has been introduced. This system combines liposomes with platelet membranes to encapsulate Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES), thus enhancing its delivery and release specifically at tumor sites. In addition, this system not only targets CSCs effectively but also increases the local concentration of BPTES upon X-ray irradiation, which reduces glutathione levels in tumor cells, thereby increasing oxidative stress and damaging mitochondria. PB-elicited mitochondrial damage as the STING signal initiator, which mediated significant upregulation in the expression of a cGAS-STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of PB remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Overall, this PB system presents a potent method to overcome CSC-related resistance and offers a promising approach for future cancer treatment protocols., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Yunnan in southwest China is a geographically and ethnically complex region at the intersection of southern China and Southeast Asia, and a focal point for human migrations. To clarify its maternal genetic history, we generated 152 complete mitogenomes from 17 Yunnan archaeological sites. Our results reveal distinct genetic histories segregated by geographical regions. Maternal lineages of ancient populations from northwestern and northern Yunnan exhibit closer affinities with past and present-day populations from northern East Asia and Tibet, providing important genetic evidence for the migration and interaction of populations along the Tibetan-Yi corridor since the Neolithic. Between 5500 to 1800 years ago, central Yunnan populations maintained their internal genetic relationships, including a 7000-year-old basal lineage of the rare and widely dispersed haplogroup M61. At the Xingyi site, changes in mitochondrial DNA haplogroups occurred between the Late Neolithic and Bronze Age, with haplogroups shifting from those predominant in the Yellow River region to those predominant in coastal southern China. These results highlight the high diversity of Yunnan populations during the Neolithic to Bronze Age., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Given the escalating demand for renewable biofuels amidst the continual consumption of fossil energy, the exploration and identification of microalgal strains for biodiesel production have become crucial. In this study, a microalgal strain named HDMA-12 was isolated from Lake Chenjiadayuan in China to evaluate its biodiesel potential. Phylogenetic analysis of its internal transcribed spacer sequences revealed HDMA-12 as a new molecular record in the genus Coelastrum . When cultivated in BG11 basal medium, HDMA-12 achieved a biomass of 635.7 mg L -1 and a lipid content of 26.4%. Furthermore, the fatty acid methyl ester profile of HDMA-12 exhibited favorable combustion characteristics. Subjected to 200 mM NaCl stress, HDMA-12 reached its maximum biomass of 751.5 mg L -1 and a lipid content of 28.9%. These findings indicate the promising prospects of HDMA-12 as a promising microalgal strain for further advancements in biodiesel production.

Soybean root rot, caused by soil-borne pathogens such as Fusarium oxysporum, frequently occurs in Northeast China and leads to a decline in soil health and becoming a bottleneck for soybean yield in the region. To address this issue, applying beneficial microorganisms and altering soil microbial community structure have become effective strategies. In this study, the 90-day soybean pot experiment was conducted to explore the assembly process and life strategy selection of bacterial communities in the rhizosphere of healthy (inoculated with Funneliformis mosseae, F group and treated with Pseudomonas putida, P group) and diseased (inoculated with F. oxysporum, O group) soybean plants, as well as the recovery effect of beneficial microorganisms on soil-borne diseases (combined treatments OP and OF). Results indicated that in healthy soils (P and F), microbial community assembly process in the soybean rhizosphere was entirely governed by heterogeneous selection (HeS, 100 %). However, inoculated with P. putida (OP) was primarily driven by stochastic processes (HeS 40 %, dispersal limitation (DL) 60 %), and the F. mosseae treatment (OF) predominantly followed a deterministic process (HeS 89 %, DL 11 %) in diseased soils. Inoculation of plant growth-promoting microorganisms (PGPMs) in diseased soil drove the life strategy of the rhizosphere bacterial community from r- to K-strategy, evident from the lower rRNA operon (rrn) copy numbers (O 3.7, OP 2.1, OF 2.3), higher G+ to G- ratios (O 0.47, OP 0.58, OF 0.57), and a higher abundance of oligotrophs (O 50 %, OP 53 %, OF 54 %). In healthy (P and F) and diseased (O, OP, OF) rhizosphere soils, OTU820, OTU6142, and OTU8841 under the K-strategy, and OTU6032 and OTU6917 under the r-strategy, which served as keystone species, had a significant promoting relationship with plant biomass and defense capabilities ( p ＜0.05). Additionally, inoculation of PGPMs improved autotoxin degradation and positively correlated with bacterial life strategies in both healthy and diseased soils (P, F, OP and OF) ( p ＜0.05). These findings enhance our understanding of soil-microbe interactions and offer new insights and precise control measures for soybean disease management and soil environment remediation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Objective: Macrophage polarization and the resulting phenotype have versatile roles in atherosclerosis. The study aims to decipher the role of SIRT1 in regulating macrophage phenotypes and atherosclerosis development., Methods: Two mouse lines of SIRT1 △Mac /ApoE -/- and SIRT1 fl/fl /ApoE -/- were fed with high-fat diet to generate atherosclerotic lesion. Mouse peritoneal macrophages were isolated and transfected with SIRT1-overexpressing vector or vector-null., Results: The SIRT1 △Mac /ApoE -/- mice exhibited greater atherosclerotic lesions, stronger immunofluorescence staining for M1-like macrophage marker, iNOS, and weaker immunofluorescence staining for M2-like macrophage marker, Arginase-1, than the SIRT1 fl/fl /ApoE -/- littermates. The gene expressions of M1 markers (IL-1β, IL-6, and iNOS) were increased and those of M2 markers (IL-10 and Arg-1) decreased in both aortic roots and peritoneal macrophages from SIRT1 △Mac /ApoE -/- mice, whereas SIRT1 overexpression rectified the changes in M1/M2 expression. A declined expression of TIMP3 with an increased expression of ADAM17 was noted in SIRT1 △Mac /ApoE -/- macrophages, whereas SIRT1 overexpression rescued TIMP3 expression and inhibited ADAM17 expression., Conclusion: Our data suggest that SIRT1 deficiency may promote macrophage M1 polarization and regulate the TIMP3/ADAM17 pathway thus favoring atherosclerosis development, indicating an anti-atherosclerotic role of macrophage SIRT1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Photothermal therapy (PTT) holds considerable clinical promise. However, insufficient PTT-induced tumor recurrence and metastasis is an urgent practical problem that needs to be solved. Herein, a biomimetic mesoporous organosilicon nano-system called PSAB is designed to precisely deplete cancer stem cells (CSCs) and prevent tumor recurrence and metastasis after PTT. The PSAB system is made up of Aggregation-induced emission (AIE)-active photothermal agent, 2TT-oC26B, and SO 2 prodrug, benzothiazole sulfinate (BTS), within mesoporous organosilicon nanoparticles (MON) enclosed by an exterior platelet membrane. PSAB effectively targets CSCs both in vitro and in vivo by P-selectin/CD44 interaction. The degradation of MON and subsequent release of BTS and AIE molecules are facilitated by intracellular glutathione (GSH). Subsequently, the acidic tumor environment triggers the SO 2 gas therapy from BTS. This process leads to the depletion of GSH and CSCs elimination. After combining PSAB with photothermal therapy, there is no significant tumor recurrence or metastasis. These results indicate that SO 2 gas therapy and AIE-mediated PTT act synergistically to offer a unique approach for preventing tumor recurrence and metastasis after PTT, thus holding significant promise for clinical applications in cancer PTT., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Blackberry polysaccharides with certain molecular weight distribution have good bioactivity. In this research, type 2 diabetes mice were used to investigate the hypoglycemic effect of blackberry polysaccharides with three different molecular weights, BBP (603.59 kDa), BBP-8 (408.13 kDa) and BBP-24 (247.62 kDa), through gut microbiota modulation. Blackberry polysaccharides exhibited stronger hypoglycemic activity after degradation, and the FBG of BBP, BBP-8 and BBP-24 was reduced to 20.21 ± 4.17 mmol L -1 , 20.6 ± 7.23 mmol L -1 and 17.32 ± 6.59 mmol L -1 and OGTT-AUC was reduced by 14.76%, 19.80% and 25.04%, respectively, after 8-week intervention. Furthermore, 16S rRNA gene sequencing analysis indicated that BBP, BBP-8 and BBP-24 could reshape the diversity and composition of the gut microbiota. From 0 to 4 weeks, the F/B of BBP, BBP-8 and BBP-24 reduced by 56.44%, 47.19% and 62.04%, reaching 3.39, 6.54, and 3.11 in the 8 th week, respectively, which suggested the faster utilization of BBP-24. Moreover, the intervention the three blackberry polysaccharides increased the relative abundance of the targeted beneficial bacteria Oscillospira and Bacteroidaceae Bacteroides and decreased the relative abundance of the pathogenic bacterium Allobaculum . In general, the result demonstrated that blackberry polysaccharides with a lower molecular weight are more easily fermented, making the theoretical basis for the development of blackberry polysaccharides as a probiotic food to rapidly regulate intestinal flora for type 2 diabetes.

Lung adenocarcinoma is the most common primary lung cancer seen in the world, and identifying genetic markers is essential for predicting the prognosis of lung adenocarcinoma and improving treatment outcomes. It is well known that alterations in circadian rhythms are associated with a higher risk of cancer. Moreover, circadian rhythms play a regulatory role in the human body. Therefore, studying the changes in circadian rhythms in cancer patients is crucial for optimizing treatment. The gene expression data and clinical data were sourced from TCGA database, and we identified the circadian clock-related genes. We used the obtained TCGA-LUAD data set to build the model, and the other 647 lung adenocarcinoma patients' data were collected from two GEO data sets for external verification. A risk score model for circadian clock-related genes was constructed, based on the identification of 8 genetically significant genes. Based on ROC analyses, the risk model demonstrated a high level of accuracy in predicting the overall survival times of lung adenocarcinoma patients in training folds, as well as external data sets. This study has successfully constructed a risk model for lung adenocarcinoma prognosis, utilizing circadian rhythm as its foundation. This model demonstrates a dependable capacity to forecast the outcome of the disease, which can further guide the relevant mechanism of lung adenocarcinoma and combine behavioral therapy with treatment to optimize treatment decision-making., (© 2024. The Author(s).)

Background: Cardiomyocyte apoptosis plays a vital role in myocardial ischemia-reperfusion (MI/R) injury; however, the role of beclin1 (BECN1) remains unclear. This study aimed at revealing the function of BECN1 during cardiomyocyte apoptosis after MI/R injury., Methods: In vivo, TTC and Evan's blue double staining was applied to verify the gross morphological alteration in both wild type (WT) mice and BECN1 transgene mice (BECN1-TG), and TUNEL staining and western blot were adopted to evaluate the cardiomyocyte apoptosis. In vitro, a hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate MI/R injury. Proteomics analysis was preformed to verify if apoptosis occurs in the H/R cellular model. And apoptosis factors, RIPK1, Caspase-1, Caspase-3, and cleaved Caspase-3, were investigated using western bolting. In addition, the mRNA level were verified using RT-PCR. To further investigate the protein interactions small interfering RNA and lentiviral transfection were used. To continue investigate the protein interactions, immunofluorescence and coimmunoprecipitation were applied., Results: Morphologically, BECN1 significantly attenuated the apoptosis from TTC-Evan's staining, TUNEL, and cardiac tissue western blot. After H/R, a RIPK1-induced complex (complex II) containing RIPK1, Caspase-8, and FADD was formed. Thereafter, cleaved Caspase-3 was activated, and myocyte apoptosis occurred. However, BECN1 decreased the expression of RIPK1, Caspase-8, and FADD. Nevertheless, BECN1 overexpression increased RIPK1 ubiquitination before apoptosis by inhibiting OTUD1., Conclusions: BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in C-Caspase-3-induced myocyte apoptosis after MI/R injury. Therefore, BECN1 can function as a cardioprotective candidate., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Concern about the zoonotic Hepatitis E virus (HEV) is rising. Since, food handlers are at greater risk in contracting HEV, the present study aims to determine awareness, knowledge, prevention practices against HEV, and immunization attitudes. A cross sectional study was conducted among 400 food handlers in Klang Valley, Malaysia from December 2021 to March 2022. A structured questionnaire was employed for data collection and analysis with Statistical Package for Social Science (SPSS) version 29. Approximately 4.5% of the respondents (18) reported having heard of HEV, while the median scores for the knowledge and practice domains were 0/10 and 1/5, respectively. A total of 316 (79%) respondents expressed willingness to obtain vaccination if made available. This study also found that those respondents who completed their tertiary education were significantly possessed better knowledge of the disease [odd ratio (OR) = 8.95, and 95% confidence interval (CI) 4.98-16.10]. Respondents with HEV awareness reported considerably better practices (OR = 8.24, 95% CI 1.72-39.63). Food handlers with one to five years of experience in the industry expressed notable willingness to take vaccination (OR = 7.71, 95% CI 1.79-33.18). Addressing poor HEV awareness and knowledge and poor practices against the disease is crucial in enlightening the policy makers about awareness among food handlers and general population. Nonetheless, a good immunization attitude, significant acceptance toward vaccination even with the vaccine being unavailable in Malaysia, and limited awareness of HEV highlight a promising development.

Improper disposal of organic solid waste results in serious environmental pollution. Aerobic composting provides an environmentally friendly treatment method, but improving humification of raw materials remains a challenge. This study revealed the effect of different concentrations of potassium persulfate (PP) on humification of chicken manure and straw aerobic composting and the underlying microbial mechanisms. The results showed that when 0.6 % PP was added (PPH group), humus and the degree of polymerization were 80.77 mg/g and 2.52, respectively, which were significantly higher than those in 0.3 % PP (PPL group). As the concentration of PP was increased, the composition of rare taxa (RT) changed and improved in evenness, while abundant taxa (AT) was unaffected. Additionally, the density (0.037), edges (3278), and average degree (15.21) in the co-occurrence network decreased compared to PPL, while the average path (4.021) and modularity increased in PPH. This resulted in facilitating the turnover of matter, information, and energy among the microbes. Interestingly, cooperative behavior between microorganisms during the maturation period (24-60 d) occurred in PPH, but competitive relationships dominated in PPL. Cooperative behavior was positively correlated with humus (p < 0.05). Because the indices, such as higher degree, betweenness centrality, eigenvector centrality, and closeness centrality of the AT, were located in the microbial network center compared to RT, they were unaffected by the concentration of PP. The abundance of carbohydrate and amino acid metabolic pathways, which play an important role in humification, were higher in PPH. These findings contribute to understanding the relative importance of composition, interactions, and metabolic functionality of RT and AT on humification during chicken manure and straw aerobic composting under different concentrations of PP, as well as provide a basic reference for use of various conditioning agents to promote humification of organic solid waste., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Despite widespread application of minimally invasive video-assisted thoracic surgery (VATS), postoperative pain following this procedure is still a constant clinical challenge. Serratus anterior plane (SAP) block is one of the regional analgesic techniques with promising outcomes. However, due to the limited duration of action, optimal analgesia is often not achieved with a single injection. We tested whether in patients who have been subjected to routine SAP block under preoperative anesthesia, the addition of a second SAP block 24 hours after surgery, improves quality of recovery, lowers postoperative opioid consumption, and reduces the prevalence of chronic pain., Methods: The present study is a single institutional, prospective, randomized, triple-blinded, placebo-controlled study. Ninety patients undergoing VATS from January 2022 to April 2022 were randomized at 1:1 ratio to receive ultrasound-guided second SAP block with 15 mL 0.375% ropivacaine (SAP block group) or 15 mL normal saline (control group) 24 hours after both groups received routine SAP block with 15 mL 0.375% ropivacaine. The primary outcome was quality of patient recovery, measured using 40-item quality of recovery questionnaire (QoR-40) at postoperative day 2 (POD 2). Secondary outcomes included: postoperative pain scores at rest, postoperative opioid consumptions, number of times that patient controlled analgesia (PCA) pump button was pressed, perioperative complications and adverse effects, prevalence of chronic pain at 2 nd and 3 rd month postoperatively, and length of hospital stay (LOS)., Results: A total of 83 patients completed the study: 43 patients in SAP block group and 40 patients in the control group. The global QoR-40 scores on POD 2 and POD 3 were significantly higher among SAP block group patients (180.07±11.34, 182.09±8.20) compared with the control group (172.18±6.15, 177.50±6.94) (P=0.01, P=0.008) respectively. Postoperative pain scores, opioid consumptions and incidence of postoperative nausea and vomiting were significantly lower among patients in SAP block group versus control group. There were no statistically significant differences in perioperative complications and LOS between the two groups. The prevalence of chronic pain at the 2 nd and 3 rd month postoperatively for patients in SAP block group and control group was 16.3%, 14%, and 32.5%, 27.5% respectively., Conclusions: In patients undergoing VATS, application of ultrasound-guided second SAP block 24 hours after surgery improved postoperative quality of life, reduced opioid consumption and related side effects, and lowered the prevalence of chronic pain., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-982/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

The self-renewal and differentiation properties of cancer stem cells (CSCs) result in chemoresistance in breast cancer. Even though numerous drugs have been developed to target CSCs, they have suffered from inefficient delivery and accumulation at the focal site. Here, a thermoresponsive hydrogel is developed by coencapsulating aggregation-induced emission (AIE)-active photothermal agent and thioridazine (THZ), demonstrating a controllable delivery system triggered by the AIE agent to augment THZ-mediated CSC ablation. Upon near-infrared laser stimuli, the photothermal effect from the AIE agent induces hydrogel deformation for burst drug release. The precise in situ tumor administration of the hydrogel accelerates drug diffusion and accumulation in deep breast cancer lesions. Thus, THZ can invade tumors and provoke massive CSC apoptosis via dopamine receptor blockage and oxidative stress induction. Consequently, effective CSC inhibition and significant suppression of tumor recurrence and metastasis are demonstrated in mice with breast cancer. We believe that this intelligent hydrogel-based delivery system represents a promising treatment strategy for metastatic breast cancer with clinical potential.

In this study, 16S rDNA high-throughput sequencing, Fourier transform infrared spectroscopy, and two-dimensional correlation spectroscopy techniques were used to analyze the mechanisms driving the sequence of degradation of gummy substances by the microbial community and hydrolytic enzymes during the flax dew degumming process. The results revealed that the inoculation of combined bacteria induced quorum sensing, modulated hydrolytic enzyme production, and reshaped the community structure. Lignin-degraded genera (Pseudomonas and Sphingobacterium) were enriched, and the relative abundances of pectin- and cellulose-degraded genera (Chryseobacterium) decreased in the early degumming stages. Hemicellulose-degraded genera (Brevundimonas) increased over the degumming time. Moreover, the abundance of lignin hydrolytic enzymes improved in the early stages, while the abundance of pectin hydrolytic enzymes increased at the end of degumming. Various types of functional bacteria taxa changed the sequence of substance degradation. Electron scanning microscopy and differential scanning calorimetry results indicated that the degumming, facilitated by the inoculation of combined bacteria, was nearly completed by 21 d. The fibers exhibited smoother and more intact properties, along with higher thermal stability, as indicated by a melting temperature of 71.54 °C. This study provides a reference for selecting precise degumming bacterial agents to enhance degumming efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Cuproptosis, a newly discovered mechanism of inducing tumor cell death, primarily relies on the intracellular accumulation of copper ions. The utilization of Cu-based nanomaterials to induce cuproptosis holds promising prospects in future biomedical applications. However, the presence of high levels of glutathione (GSH) within tumor cells hinders the efficacy of cuproptosis. In this study, we have developed a BPTES-loaded biomimetic Cu-doped polypyrrole nanoparticles (CuP) nanosystem (PCB) for enhanced cuproptosis and immune modulation. PCB comprises an internal BPTES and CuP core and an external platelet membrane (PM) that facilitates active targeting to tumor sites following intravenous administration. Subsequently, PCB effectively suppresses glutaminase (GLS1) activity, thereby reducing GSH content. Moreover, CuP catalyze intracellular H 2 O 2 , amplifying oxidative stress while simultaneously inducing dihydrolipoyl transacetylase (DLAT) oligomerization through released Cu 2+ , resulting in cuproptosis. PCB not only inhibits primary tumors but also exhibits inhibitory effects on abscopal tumors. This work represents the first instance where GLS inhibition has been employed to enhance cuproptosis and immunotherapy. It also provides valuable insights into further investigations on cuproptosis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the associations between career choice motivation and professionalism among medical students based on gender in the context of COVID-19., Design: Cross-sectional study., Setting: The study was conducted at a medical school in China., Methods: A total of 1421 second-year to fourth-year medical students participated in the survey using cluster sampling. They were asked to complete questionnaires on demographic information, career choice motivation and professionalism. Linear regression models were used to analyse the relationship between career choice motivations and professionalism based on gender differences., Results: Female medical students outperformed males in professionalism (p<0.001). Third-year medical students have the lowest level of professionalism irrespective of gender. In addition, females have more intrinsic career choice motivation than males. Students motivated by personal interest had the highest level of professionalism, while those who go with the flow had the lowest. According to the linear regression analysis, the motivation advice from parents was the factor of professionalism in male medical students (p<0.05). However, the motivation go with the flow negatively influenced the professionalism of female medical students (p<0.05)., Conclusion: The level of professionalism differed between genders based on different career choice motivations. Career choice motivation can be used as an entry point for professionalism education among medical students. Targeted interventions should be implemented to improve professionalism, especially for male medical students and unmotivated students., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Reduced cardiorespiratory fitness levels are associated with increased short-term complications after surgery, and potentially exert long-lasting effects on the postoperative lives, work and educational pursuits of patients. Currently, research suggests that lifestyle interventions, such as preoperative physical exercise undertaken by patients themselves, may improve patients' cardiopulmonary fitness and reduce post-operative complications. This study aims to investigate the effectiveness and feasibility of a remote medical supervision model for prehabilitation exercise in patients undergoing thoracoscopic lung tumour resection surgery., Methods/design: All enrolled patients will participate in a 4-week pre-operative exercise intervention to improve their cardiorespiratory fitness. During this period, patients will wear wearable devices and exercise at home based on exercise prescriptions. The exercise prescription comprises aerobic exercise (three times a week or more), muscle strengthening exercise (twice a week or more), and respiratory muscle exercise (once a day). The primary aim is to investigate whether baseline VO 2 max could be improved following a 4-week preoperative exercise program. Secondary objectives include changes in forced expiratory volume in 1 s and forced vital capacity, degree of acceptance of the technology, quality of life, handgrip strength, postoperative complication rate and length of hospital stay., Discussion: This study aims to evaluate the influence of preoperative prehabilitation exercises in a telemedicine active supervision mode in patients undergoing thoracoscopic lung tumour resection. As such, results of this trial might have some impact on future implementations of group- and home-based prehabilitation exercises in lung cancers., Trial Registration: This study was approved by the Medical Ethics Committee of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (approval number: TJ-IRB20220564) with registration at ClinicalTrials.gov (identifier: NCT05608759)., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Sunscreens play a crucial role in protecting the skin from ultraviolet (UV) damage. However, present commercial sunscreens have a tendency to generate free radicals in the UV window, resulting in serious inflammatory responses and health problems. In this study, we demonstrate that silk fibroin microspheres (SFMPs) assembled from regenerated silk fibroin (SF) could scavenge free radicals while preventing UV irradiation and thus present a promising sunscreen. The SFMP reflected more UV light than SF and presented a higher stability than that of organic commercial sunscreens. In vitro analysis proved that SFMP could more efficiently scavenge the hydroxy radical and reduce the intracellular reactive oxygen than titanium dioxide (TiO 2 ). In vivo experiments exhibited that SFMP provided stronger skin protection against UV irradiation than commercial sunscreens and TiO 2 . Furthermore, SFMP treatment significantly inhibited the skin inflammatory response. This work suggests that the SFMP has great potential to be developed into a biosafe sunscreen.

Aerobic composting increases the content of soluble nutrients and facilitates the safe treatment of livestock manure. Although different taxa play crucial roles in maintaining ecological functionality, the succession patterns of community composition and assembly of rare and abundant subcommunities during aerobic composting under antibiotic stress and their contributions to ecosystem functionality remain unclear. Therefore, this study used 16 S rRNA gene sequencing technology to reveal the response mechanisms of diverse microbial communities and the assembly processes of abundant and rare taxa to amoxicillin during aerobic composting. The results indicated that rare taxa exhibited distinct advantages in terms of diversity, community composition, and ecological niche width compared with abundant taxa, highlighting their significance in maintaining ecological community dynamics. In addition, deterministic (heterogeneous selection) and stochastic processes (dispersal limitation) play roles in the community succession and functional dynamics of abundant and rare subcommunities. The findings of this study may contribute to a better understanding of the relative importance of deterministic and stochastic assembly processes in composting systems, and the ecological functions of diverse microbial communities, ultimately leading to improved ecological environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

This study aims to investigate the significance of using the Toumai robotic platform for the resection of inferior vena cava (IVC) hemangiomas. Our objective is to provide information on the potential benefits of this innovative approach in managing these uncommon vascular tumors and to contribute to the growing body of knowledge in the field of surgical oncology and vascular surgery. A 37-year-old female patient with an incidental finding of a right retroperitoneal mass underwent contrast-enhanced magnetic resonance imaging, which confirmed the diagnosis of an IVC hemangioma. Due to the rarity and complexity of this vascular tumor, the medical team opted for a novel approach using the Toumai robotic surgical platform (Shanghai MicroPort MedBot Group Co, Ltd). Under general anesthesia, the patient was placed in the left lateral decubitus position, and the robotic arms were controlled remotely through the Toumai platform. A transperitoneal approach was adopted, and the surgeon meticulously resected the tumor while preserving the integrity of the IVC. The use of the Toumai robotic platform facilitated precise tumor resection, minimizing the risk of damage to surrounding structures. The minimally invasive nature of the robotic surgery contributed to a reduced incidence of postoperative complications and accelerated patient recovery. Furthermore, the remote fifth-generation mobile network surgical capabilities of the Toumai platform allow for expert care to be provided to patients despite geographic barriers. The robotic-assisted surgical approach using the Toumai platform demonstrates its potential benefits in managing rare and complex vascular tumors such as IVC hemangiomas. Robotic technology has the potential to revolutionize the field of surgical oncology and vascular surgery, leading to improved patient outcomes and healthcare delivery. However, more extensive clinical studies and larger case series are needed to validate the long-term safety and efficacy of this innovative surgical approach. Continued research and collaboration between clinicians and robotic technology experts are essential to fully realize the potential of robotic-assisted surgery for the benefit of patients with rare and challenging medical conditions., Competing Interests: None., (© 2023 The Authors.)

In this paper, a low-temperature thick oil demulsifier with high polarity was prepared by introducing ethylene oxide, propylene oxide block, and butylene oxide using m-diphenol as a starting agent. The main reasons for the difficulty involved in the low-temperature emulsification of extractive fluids were explained by analyzing the synthetic influencing factors and infrared spectra of the star comb polymer (PR-D2) and by analyzing the four fractions, interfacial energies, and zeta potentials of crude oils from the Chun and Gao fields. The effects of PR-D2 surfactant on the emulsification performance of crude oil recovery fluids were investigated via indoor and field experiments. The experimental results indicate that the optimal synthesis conditions for this emulsion breaker are as follows: a quality ratio of ionic reaction intermediates and meso-diphenol of R = 10:1; 1 g of the initiator; a polymerization temperature of 80 °C; and a reaction time of 8 h. Colloidal asphaltenes in the crude oil were the main factor hindering the low-temperature demulsification of the Gao oilfield's extractive fluids, and the reason for the demulsification difficulty of the extractive fluids in the Chun oilfield is that the temperature of demulsification is lower than the wax precipitation point. The demulsification rate of the Chun oilfield's extractive fluids reached more than 98% when the PR-D2 concentration reached 150 mg/L at 43 °C. The demulsification rate of the Gao oilfield's extractive fluids reached more than 98% at a PR-D2 concentration of 150 mg/L at 65 °C. The field experiments show that the Chun oilfield's extractive fluids can still demulsify after the temperature is reduced to 43 °C in winter. The emulsification temperature of the Gao oilfield's extractive fluids was reduced from 73 °C to 68 °C, with an excellent demulsification effect.

Background: Although end-of-life care (EOLC) has been well-studied, the experience of neonatal intensive care unit (NICU) nurses in China, where little EOLC training is provided, requires further investigation., Purpose: To explore the lived experience of EOLC delivery among NICU nurses, to provide evidence to enhance nurses' EOLC skills and improve their overall quality., Methods: This qualitative study adopted a phenomenological approach. A total of 11 NICU nurses participated in semistructured in-depth interviews between June and July 2022 at the First Affiliated Hospital of University of Science and Technology of China (USTC). Colaizzi's 7-step method was used to analyze the data., Results: Five main themes were identified: (a) multiple emotions are experienced during EOLC delivery; (b) EOLC delivery is stressful from various sources for nurses; (c) expressing empathy and compassion is important; (d) ethical and clinical decision-making are key components of EOLC delivery; and (e) there are challenges in improving neonatal EOLC understanding and delivery., Implications for Practice and Research: The experience of EOLC among Chinese NICU nurses is multidimensional and intensive. Institutions or units must establish and implement related protocols and guidelines to address differences between clinical practice and ideal protocols for neonatal EOLC. Educational programs that consider nurses' personal and interpersonal factors, including local culture, must be developed. Neonatal nurses in Western countries encountering Chinese-born parents who have lost their infants can gain an understanding of parents' perceptions from this study. Future research should focus on developing and testing interventions to train and support NICU nurses working with end-of-life neonates., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 by The National Association of Neonatal Nurses.)

To explore the response of soil metabolite composition to soybean disease, the effect of the combined inoculation of arbuscular mycorrhizal fungi (AMF) and plant growth-promoting bacteria on soybean root rot caused by Fusarium oxysporum was studied. A factorial completely randomized design with three factors (AMF, Bacillus. paramycoides, and rot disease stress) was conducted, and eight treatments, including normal groups and stress groups, were performed using pot experiments. GC‒MS and enzymatic assays were used to evaluate the soil factors and soybean growth indicators. The results showed that there were significant differences in the composition of metabolites among the different treatment groups, and 23 metabolites were significantly related to soybean biomass. The combined inoculation of Funneliformis mosseae and Bacillus paramycoides resulted in a significant reduction in harmful soil metabolites associated with root rot disease, such as ethylbenzene and styrene. This reduction in metabolites contributed to improving soil health, as evidenced by enhanced soybean defence enzyme activities and microbial activity, and β-1,3-glucanase, chitinase and phenylalanine ammonia-lyase activities were improved to alleviate plant rhizosphere stress. Furthermore, soybean plants inoculated with the synergistic treatments exhibited reduced root rot disease severity and improved growth indicators compared to control plants. Plant height, root dry weight (RDW), and shoot and root fresh weight (SRFW) were improved by 4.18-53.79%, and the AM fungal colonization rate was also improved under stress. The synergistic application of Funneliformis mosseae and Bacillus paramycoides can effectively enhance soil health by inhibiting the production of harmful soil metabolites and improving soybean tolerance to root rot disease. This approach holds promise for the sustainable management of soil-borne diseases in soybean cultivation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The diagnostic criteria for abdominal obesity are usually waist circumference or waist-to-hip ratio. The magnitude of the risks for cancers of the digestive system and abdominal obesity is unknown. To assess whether abdominal obesity increases the risk of digestive cancer, we conducted a systematic review and meta-analysis of prospective cohort studies in a database., Methods: PubMed, Embase, and Web of Science databases were searched from their inception to December 2022. The 9-star Newcastle Ottawa Scale was used to assess  study quality. Pooled relative risks and 95% confidence intervals were calculated using fixed or random effect models respectively. The stability of the results was explored by one-by-one exclusion. Subgroup analysis was conducted to explore sources of heterogeneity. Publication bias was evaluated by Begg's and Egger's tests., Results: A total of 43 cohort studies were included. There were 42 and 31 studies in the meta-analysis of waist circumference and waist-to-hip ratio on digestive system cancer, respectively. The results of the meta-analysis revealed that the greater waist circumference and waist-to-hip ratio were correlated with increased incidence of digestive system cancers: waist circumference: RR 1.48, 95% CI 1.38-1.59, p < 0.001; waist-to-hip ratio: RR 1.33, 95% CI 1.28-1.38, p = 0.001. Subgroup analysis by cancer type showed that higher WC and WHR would increase the prevalence of LC, PC, GC, EC, and CRC. The sensitivity analysis was conducted by a one-by-one elimination method, and the results of the meta-analysis remained stable. It is proved that the results were robust by the trim-and-fill method., Conclusions: There was evidence to suggest that abdominal obesity increased the incidence of digestive cancer, it is necessary to take appropriate measures to reduce abdominal obesity. Waist circumference and waist-to-hip ratio may be better predictors of digestive system cancers. However, the association between waist circumference and digestive system cancer was greater, so more attention should be paid to measuring abdominal obesity with waist circumference., (© 2023. The Author(s).)

Polycomb repressive complex 1 (PRC1) comprises two different complexes: CBX-containing canonical PRC1 (cPRC1) and RYBP/YAF2-containing variant PRC1 (vPRC1). RYBP-vPRC1 or YAF2-vPRC1 catalyzes H2AK119ub through a positive-feedback model; however, whether RYBP and YAF2 have different regulatory functions is still unclear. Here, we show that the expression of RYBP and YAF2 decreases and increases, respectively, during neural differentiation of embryonic stem cells (ESCs). Rybp knockout impairs neural differentiation by activating Wnt signaling and derepressing nonneuroectoderm-associated genes. However, Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding, increases enrichment of RYBP and H2AK119ub on the RYBP-YAF2 cotargeted genes, and prevents ectopic derepression of nonneuroectoderm-associated genes in neural-differentiated cells. Taken together, this study reveals that RYBP and YAF2 function differentially in regulating mESC neural differentiation., (© 2023. The Author(s).)

Increasing evidence suggests that the pathogenesis of type 2 diabetes mellitus (T2DM) is closely related to the gut microbiota. Polyphenols have been shown to alleviate T2DM, but the effects of L. caerulea L. polyphenols (LPs) on the gut microbiota and metabolites remain elusive. In this study, the inhibitory effects of fermented L. caerulea L. polyphenols (FLPs) and unfermented L. caerulea L. polyphenols (ULPs) on α-amylase and α-glucosidase and the impact of LP on the gut microbiota and metabolites were investigated. Furthermore, the relationship between the two was revealed through correlation analysis. The results showed that ULP and FLP had the highest inhibitory rates against α-amylase and α-glucosidase at 4 mg ml -1 , indicating a strong inhibitory ability. In addition, LP plays a regulatory role in the concentration of short-chain fatty acids (SCFAs) and tends to restore them to their normal levels. LP reversed the dysbiosis of the gut microbiota caused by T2DM, as evidenced by an increase in the abundance of bacterial genera such as Lactobacillus , Blautia , and Bacteroides and a decrease in the abundance of bacterial genera such as Escherichia-Shigella and Streptococcus . Similarly, after LP intervention, the relationships among microbial species became more complex and interconnected. In addition, the correlation between the gut microbiota and metabolites was established through correlation analysis. These further findings clarify the mechanism of action of LP against T2DM and provide a new target for T2DM interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, Wang, Ren, Sun, Yang, Ge and Ping.)

Objectives: The current study aimed at ascertaining the depression levels of medical students and their knowledge levels of depression, and exploring the relationship between the level of knowledge and coping styles of the medical students on depression., Methods: An online-based survey was developed in Changzhi Medical College. The questionnaire included demographic and socioeconomic data, questions about depression knowledge and copying styles of depression, and the Zung Self-Rating Depression Scale (SDS). A total of 1931 questionnaires were returned by respondents., Results: The medical students produced a mean SDS score of 44.29 (SD = 11.67). The prevalence of depression was 29.7%. Sophomore, female, and poor family relationships were parameters associated with a higher SDS score. The total correct rate for knowledge of depression was 64.14%. There were statistical differences between with depression students and non-depression students on the rate of the correct answers in the following questions:"Female has more probability", "Depression can be adjusted by oneself", "Associated with one's character", "Know cure method of depression", "Know drug use of depression", "Know depression influence for health", and "Know prevention method of depression". Depression students were more likely to have a lower rate of correct answer for above questions. Asking for help from psychological consultation was the primary coping mechanism among the medical students. The logistic regression analysis results found that depressed students who chose the coping way of no ways of coping were more likely to be females OR = 1.470 (1.078, 2.005), residents in rural area OR = 1.496 (1.038, 2.156), in poor family relationships OR = 2.428 (1.790, 3.293), and have lower cognitive level of depression knowledge OR = 1.920 (1.426, 3.226)., Conclusions: It is necessary to focus on mental health of medical students, especially in female, residents in rural area, in poor family relationships, and having lower cognitive level of depression knowledge. Medical students were insufficient on depression knowledge and coping styles, and efforts that train students know risk of impaired mental health could also improve diagnosis and treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The settlement of the Tibetan Plateau epitomizes human adaptation to a high-altitude environment that poses great challenges to human activity. Here, we reconstruct a 4000-year maternal genetic history of Tibetans using 128 ancient mitochondrial genome data from 37 sites in Tibet. The phylogeny of haplotypes M9a1a, M9a1b, D4g2, G2a'c, and D4i show that ancient Tibetans share the most recent common ancestor with ancient Middle and Upper Yellow River populations around the Early and Middle Holocene. In addition, the connections between Tibetans and Northeastern Asians vary over the past 4000 years, with a stronger matrilineal connection between the two during 4000 BP-3000 BP, and a weakened connection after 3000 BP, that are coincident with climate change, followed by a reinforced connection after the Tubo period (1400 BP-1100 BP). Besides, an over 4000-year matrilineal continuity is observed in some of the maternal lineages. We also find the maternal genetic structure of ancient Tibetans is correlated to the geography and interactions between ancient Tibetans and ancient Nepal and Pakistan populations. Overall, the maternal genetic history of Tibetans can be characterized as a long-term matrilineal continuity with frequent internal and external population interactions that are dynamically shaped by geography, climate changes, as well as historical events., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tissue engineering approaches offer promising alternative strategies for reconstructing bladder tissue; however, the low retention of transplanted cells and the possible risk of rejection limit their therapeutic efficacy. Clinical applicability is further limited by the lack of suitable scaffold materials to support the needs of various cell types. In the present study, we developed an artificial nanoscaffold system consisting of stromal vascular fraction (SVF) secretome (Sec) loaded onto zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, which were then incorporated into bladder acellular matrix. This artificial acellular nanocomposite scaffold (ANS) can achieve gradient degradation and slowly release SVF-Sec to promote tissue regeneration. Furthermore, even after long-term cryopreservation, this completely acellular bladder nanoscaffold material still maintains its efficacy. In a rat bladder replacement model, ANS transplantation demonstrated potent proangiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function. Our study demonstrates the safety and efficacy of the ANS, which can play a stem cell-like role while avoiding the disadvantages of cell therapy. Furthermore, the ANS can replace the bladder regeneration model based on cell-binding scaffold materials and has the potential for clinical application. STATEMENT OF SIGNIFICANCE: This study aimed to develop a gradient-degradable artificial acellular nanocomposite scaffold (ANS) loaded with stromal vascular fraction (SVF) secretome for rehabilitating bladders. Using various in vitro methods as well as rat- and zebrafish-based in vivo models, the developed ANS was assessed for efficacy and safety. Results indicated that the ANS achieved gradient degradation and slowly released the SVF secretome to promote tissue regeneration, even after long-term cryopreservation. Furthermore, ANS transplantation demonstrated a potent pro-angiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function in a bladder replacement model. Our study demonstrates that ANS may replace bladder regeneration models based on cell-binding scaffold materials and have potential clinical application., Competing Interests: Declaration of Interest Statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Cardiovascular disease is the greatest health care burden and one of the most common causes of death worldwide. Less is known about the genetic factors that are responsible for predisposition to cardiovascular disease thus; the molecular and genetic mechanisms underlying cardiovascular diseases remain obscure. One important regulator of blood pressure homeostasis is the renin-angiotensin system. The protease renin cleaves angiotensinogen into the inactive decameric peptide angiotensin I (Ang I). Angiotensin-converting enzyme (ACE) catalyzes the cleavage of the Ang I into the active octomer angiotensin II (Ang II). In humans, can ACE polymorphism has been associated with determinants of renal and cardiovascular function and pharmacological inhibition of ACE and Ang II receptors are effective in lowering blood pressure and preventing kidney disease. In addition, inhibition of ACE and Ang II receptors has beneficial effects in heart failure. A homologue of ACE, termed ACE2, has been identified; it is predominantly expressed in the vascular endothelial cells of the kidney and heart. Unlike ACE, ACE2 functions as a carboxypeptidase, cleaving a single residue from AngI, generating Ang1-9, and a single residue from AngII to generate Ang1-7. Nevertheless, the in vivo role of ACE2 in the cardiovascular system and the renin-angiotensin system is not known., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this study, an exopolysaccharide (EPS)-producing strain of Lactiplantibacillus plantarum HDC-01 was isolated from sauerkraut, and the structure, properties and biological activity of the studied EPS were assessed. The molecular weight of the isolated EPS is 2.505 × 10 6 Da. Fourier transform infrared spectrometry (FT-IR) and nuclear magnetic resonance (NMR) results showed that the EPS was composed of glucose/glucopyranose subunits linked by an α -(1 → 6) glycosidic bond and contained an α -(1 → 3) branching structure. X-ray diffraction (XRD) analysis revealed the amorphous nature of the EPS. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that the isolated EPS had a smooth and compact surface with several protrusions of varying lengths and irregularly shaped material. Moreover, the studied EPS showed good thermal stability, water holding capacity, and milk coagulation ability and promoted the growth of probiotics. L. plantarum EPS may be used as prebiotics in the fields of food and medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Ye, Qi, Yang, Zhou, Zhang, Du, Ge and Ping.)

Cellular totipotency is critical for whole-organism generation, yet how totipotency is established remains poorly illustrated. Abundant transposable elements (TEs) are activated in totipotent cells, which is critical for embryonic totipotency. Here, we show that the histone chaperone RBBP4, but not its homolog RBBP7, is indispensable for maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms mESCs to the totipotent 2C-like cells. Also, loss of RBBP4 enhances transition from mESCs to trophoblast cells. Mechanistically, RBBP4 binds to the endogenous retroviruses (ERVs) and functions as an upstream regulator by recruiting G9a to deposit H3K9me2 on ERVL elements, and recruiting KAP1 to deposit H3K9me3 on ERV1/ERVK elements, respectively. Moreover, RBBP4 facilitates the maintenance of nucleosome occupancy at the ERVK and ERVL sites within heterochromatin regions through the chromatin remodeler CHD4. RBBP4 depletion leads to the loss of the heterochromatin marks and activation of TEs and 2C genes. Together, our findings illustrate that RBBP4 is required for heterochromatin assembly and is a critical barrier for inducing cell fate transition from pluripotency to totipotency., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

To explore the effect of Lonicera caerulea fruit polyphenols (LCP) on caries-causing bacteria, strain RYX-01 with high production of biofilm and exopolysaccharides (EPS) was isolated from the oral cavity of caries patients and was identified as Lactobacillus rhamnosus by 16S rDNA analysis and morphology. The characteristics of EPS produced by RYX-01 (EPS-CK) and those produced by adding L. caerulea fruit polyphenols (EPS-LCP) were compared to reveal whether LCP reduced the cariogenicity of RYX-01 by influencing the structure and composition of EPS. The results showed that LCP could increase the content of galactose in EPS and destroy the original aggregation state of EPS-CK but had no significant effect on the molecular weight and functional group composition of EPS (p > 0.05). At the same time, LCP could inhibit the growth of RYX-01, reduce EPS and biofilm formation and inhibit the expression of quorum sensing (QS, luxS)- and biofilm formation (wzb)-related genes. Therefore, LCP could change the surface morphology, content and composition of RYX-01 EPS and reduce the cariogenic effect of EPS and biofilm. In conclusion, LCP can be used as a potential plaque biofilm inhibitor and QS inhibitor in drugs and functional foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design., Methods and Findings: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-"Low" Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-"Medium" Watch), 18.0% (n = 566) started a carbapenem (Group 4-"High" Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability., Conclusion: Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis., Trial Registration: ClinicalTrials.gov, (NCT03721302)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Members of the funder (MB, NK, SE) participated as authors on the study, reviewed the manuscript, and approved the final manuscript as submitted. All other authors have declared that no competing interests exist., (Copyright: © 2023 Russell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network.

Aerobic composting renders the sauerkraut fermentation waste water harmless while adding soluble nutrients. Unravelling the bacterial community assembly processes, changes in community robustness and community cohesion and the relationship between them under composting treatment of sauerkraut fermentation waste water is an interesting topic. Sauerkraut fermentation waste water was used for composting, which increased bacterial linkages, community robustness, competitive behaviour during warming periods and cooperative behaviour during cooling periods, and the control of community assembly processes shifts from deterministic processes (variable selection) to stochastic processes (decentralised limitation). At the same time, the influence of community robustness and community cohesion on community assembly processes was increased. Community cohesion and robustness were significantly correlated with community function. These results indicate that community robustness and community cohesion are critical for the biological handling of hazardous substances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Heterobasidion annosum is one of the most aggressive pathogens of Pinus forests in Europe, causing considerable economic losses. To detect H. annosum for disease diagnosis and control, we developed a loop-mediated isothermal amplification (LAMP) reaction with a primer set designed from the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) DNA sequences of H. annosum . In our study, this LAMP assay was found to be capable of efficiently amplifying the target gene within 60 min at 63°C. In specificity tests, H. annosum was positively detected, and other species were negative. The detection limit of this assay was found to be 100 pg·μL -1 , and the assay was also successfully tested for use with basidiospore suspensions and wood samples. This study provides a rapid method for diagnosing root and butt rot caused by H. annosum , which will be of use in port surveillance of logs imported from Europe., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hong-min, Jian, Ying, Yuan, Cui-ping, Yu-cheng and Jia-jia.)

Background: Bone is the most common site of metastatic breast cancer (MBC). EDTA is often used to decalcify bony tissue samples to ensure the accurate assessment of antigenicity in MBC. It takes ~24 to 48 hours to decalcify small bone tissues such as bone marrow, which is considered unacceptable given the priority that is often placed on the rapid processing of bone marrow trephine cores. Thus, an effective decalcification method that preserves genetic material is needed., Aim: We performed immunohistochemical studies on surface decalcification (SD) in breast tumors and evaluated the effect of SD on receptor status and human epidermal growth factor receptor 2 (HER2). Fluorescence in situ hybridization was performed on a subset of these tumors to establish a protocol for handling bone specimens for MBC., Materials and Methods: Forty-four cases of invasive breast tumors were studied. We compared the immunohistochemical expressions of estrogen receptor (ER), progesterone receptor (PR), Ki67, and HER2 between control tissue (nondecalcified) and parallel tissue subjected to SD with hydrochloric acid. We also evaluated the effect of SD on the fluorescence in situ hybridization expression of HER2., Results: Categorical decreases in ER and PR expression were identified in 9/31 (29.0%) cases without SD and 10/26 (38.5%) cases with SD. HER2 expression changed from equivocal to negative in 4/12 (33.4%) cases. Among the HER2-positive cases, all remained positive after SD. The most significant declines in immunoreactivity occurred with Ki67, with an average decrease from 22% to 13%. The average HER2 copy numbers were 5.37 and 4.76 in the control and SD groups, respectively, and the average HER2/CEP17 ratios were 2.35 and 2.08, respectively., Conclusions: Overall, SD is an alternative decalcification method in bony metastases to assess ER, PR, and HER2 in MBC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Using genome-wide data of 89 ancient individuals dated to 5100 to 100 years before the present (B.P.) from 29 sites across the Tibetan Plateau, we found plateau-specific ancestry across plateau populations, with substantial genetic structure indicating high differentiation before 2500 B.P. Northeastern plateau populations rapidly showed admixture associated with millet farmers by 4700 B.P. in the Gonghe Basin. High genetic similarity on the southern and southwestern plateau showed population expansion along the Yarlung Tsangpo River since 3400 years ago. Central and southeastern plateau populations revealed extensive genetic admixture within the plateau historically, with substantial ancestry related to that found in southern and southwestern plateau populations. Over the past ~700 years, substantial gene flow from lowland East Asia further shaped the genetic landscape of present-day plateau populations. The high-altitude adaptive EPAS1 allele was found in plateau populations as early as in a 5100-year-old individual and showed a sharp increase over the past 2800 years.

Background: Depressive symptoms are a serious public health problem that affects the mental health of older adults. However, current knowledge of the association between ADL disability and physical dysfunction and depressive symptoms in Chinese adults is insufficient. We intend to analyze the association between physical function, ADL, and depressive symptoms in older Chinese adults., Methods: The data obtained from the China Health and Retirement Longitudinal Survey (2015 and 2018) (CHARLS). This includes 3,431 in 2015 and 3,258 in 2018 over the age of 60. Comparing 2015 and 2018 data, multivariate logistic regression models were used to explore the relationship between physical function, ADL, and depressive symptoms in urban and rural older adults, adjusting for sociodemographic factors associated with depression in older adults., Results: The prevalence of depressive symptoms among older adults in China was 33.8 percent in 2015 and 50.6 percent in 2018. In baseline data from 2015 and 2018, residence, gender, marital status, drinking, physical function, ADL, and self-rated health were all found to be significantly associated with depressive symptoms in older adults. The differences in physical function, ADL and depressive symptoms among older adults in 2015 and 2018 were further analyzed based on urban and rural stratification. Both physical dysfunction and ADL disability were significantly associated with depressive symptoms in rural older adults in 2015 and 2018. And in urban areas, ADL was found to be significantly associated with depressive symptoms in urban older adults. Multivariate logistic regression analysis demonstrated that ADL disability was significantly associated with depressive symptoms among older adults in both urban and rural areas. Physical dysfunction was only significant in rural areas with depressive symptoms. The alpha level was instead set to 0.05 for all statistical tests., Conclusion: Rural, female, 60-70 years of age, primary school or below, married, non-smoking, non-drinking, physical dysfunction, ADL disability and self-rated poor health make-up a higher proportion of depressed older adults. ADL disability and physical dysfunction were more likely to be associated with depressive symptoms in rural Chinese older adults. Therefore, the physical and mental health of rural elderly should be of concern. The rural older adults should receive additional support from the government and society., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yan, Du, Li, Ping and Chang.)

Nowadays, the world has achieved tremendous economic development at the expense of the long-term habitability of the planet. With the rapid economic development, the global greenhouse effect caused by excessive carbon dioxide (CO 2 ) emissions is also accumulating, which generates the negative impact of global warming on nature and human beings. Meanwhile, economy and CO 2 emissions prediction methods based on traditional neural networks lead to gradient disappearance or gradient explosion, making the economy and CO 2 emissions prediction inaccurate. Therefore, this paper proposes a novel economy and CO 2 emissions prediction model based on a residual neural network (RESNET) to optimize and analyze energy structures of different countries or regions in the world. The skip links are used in the inner residual block of the RESNET to alleviate vanishing gradients due to increasing depth in deep neural networks. Consequently, the proposed RESNET can optimize this problem and protect the integrity of information by directly bypassing the input information to the output, which can increase the precision of the prediction model. The needs for natural gas, hydroelectricity, oil, coal, nuclear energy, and renewable energy in 24 different countries or regions from 2009 to 2020 are used as inputs, the CO 2 emissions and the gross domestic product (GDP) per capita are respectively used as the undesired output and the desired output of the RESNET to build an economy and CO 2 emissions prediction model. The experimental results show that the RESNET has higher correctness and functionality than the traditional convolutional neural network (CNN), the radial basis function (RBF), the extreme learning machine (ELM) and the back propagation (BP). Furthermore, the proposed model provides guidance and development plans for countries or regions with low energy efficiency, which can improve energy efficiency, economic development and reasonably control CO 2 emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)