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Abstract Caspase-8, a renowned cysteine-aspartic protease within its enzyme family, initially garnered attention for its regulatory role in extrinsic apoptosis. With advancing research, a growing body of evidence has substantiated its involvement in other cell death processes, such as pyroptosis and necroptosis, as well as its modulatory effects on inflammasomes and proinflammatory cytokines. PANoptosis, an emerging concept of cell death, encompasses pyroptosis, apoptosis, and necroptosis, providing insight into the often overlapping cellular mortality observed during disease progression. The activation or deficiency of caspase-8 enzymatic activity is closely linked to PANoptosis, positioning caspase-8 as a key regulator of cell survival or death across various physiological and pathological processes. Aberrant expression of caspase-8 is closely associated with the development and progression of a range of inflammatory diseases, including immune system disorders, neurodegenerative diseases (NDDs), sepsis, and cancer. This paper delves into the regulatory role and impact of caspase-8 in these conditions, aiming to elucidate potential therapeutic strategies for the future intervention.

Abstract Background Dysbiosis of the microbiome is a key hallmark of polycystic ovary syndrome (PCOS). However, the interaction between the host and microbiome and its relevance to the pathogenesis of PCOS remain unclear. Methods To evaluate the role of the commensal gut microbiome in PCOS, we gavaged germ-free mice with the fecal microbiota from patients with PCOS or healthy individuals and evaluated the reproductive endocrine features of the recipient mice. Results Mice transplanted with fecal microbiota from PCOS patients and those transplanted from healthy controls presented different bacterial profiles and reproductive endocrine features. The fecal microbiota of the mice in the PCOS group was enriched in Phocaeicola, Mediterraneibacter, Oscillospiraceae, Lawsonibacter and Rikenellaceae. Fecal microbiota transplantation (FMT) from PCOS patients induced increased disruption of ovarian functions, lipo-metabolic disturbance, insulin resistance and an obese-like phenotype in recipient mice. Conclusion Our findings suggest that the microbiome may govern the set point of PCOS-bearing individuals and that gut ecosystem manipulation may be a useful marker and target for the management of PCOS.

Abstract Metabolic remodeling is a strategy for tumor survival under stress. However, the molecular mechanisms during the metabolic remodeling of colorectal cancer (CRC) remain unclear. Melanocyte proliferating gene 1 (MYG1) is a 3′−5′ RNA exonuclease and plays a key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease activity. Mechanistically, nuclear MYG1 recruits HSP90/GSK3β complex to promote PKM2 phosphorylation, increasing its stability. PKM2 transcriptionally activates MYC and promotes MYC-medicated glycolysis. Conversely, c-Myc also transcriptionally upregulates MYG1, driving the progression of CRC. Meanwhile, mitochondrial MYG1 on the one hand inhibits oxidative phosphorylation (OXPHOS), and on the other hand blocks the release of Cyt c from mitochondria and inhibits cell apoptosis. Clinically, patients with KRAS mutation show high expression of MYG1, indicating a high level of glycolysis and a poor prognosis. Targeting MYG1 may disturb metabolic balance of CRC and serve as a potential target for the diagnosis and treatment of CRC.

Abstract Dispersionless flat bands (FBs) in momentum space, given rise to electron destructive interference in frustrated lattices, offer opportunities to enhance electronic correlations and host exotic many‐body phenomena, such as Wigner crystal, fractional quantum hall state, and superconductivity. Despite successes in theory, great challenges remain in experimentally realizing FBs in frustrated lattices due to thermodynamically structural instability. Here, the observation of electronic FB in a potassium distorted colouring triangle (DCT) lattice is reported, which is supported on a blue phosphorene‐gold network. It is verified that the interaction between potassium and the underlayer dominates and stabilizes the frustrated structures. Two‐dimensional electron gas is modulated by the DCT lattice, and in turn results in a FB dispersion due to destructive quantum interferences. The FB exhibits suppressed bandwidth with high density of states, which is directly observed by scanning tunneling microscopy and confirmed by the first‐principles calculation. This work demonstrates that DCT lattice is a promising platform to study FB physics and explore exotic phenomena of correlation and topological matters.

BackgroundPrior research suggests a potential link between ABO blood types and susceptibility to various malignancies. The correlation between ABO blood types and hematological myeloid neoplasms, however, remains inadequately explored.ObjectiveThis study investigates the association between ABO blood groups and the incidence of hematological myeloid neoplasms in adolescents and adults.MethodsIn this retrospective clinical study, 1,022 adolescent and adult cases of myeloid neoplasms diagnosed at our institution were initially considered. After excluding conditions potentially linked to ABO blood types from prior studies, 792 eligible cases were analyzed. These cases were categorized based on disease subtypes and compared with a control group for blood type distribution.ResultsOur findings reveal a significantly higher prevalence of blood type A in patients with myeloid neoplasms compared to the control group, except for chronic myelocytic leukemia and myeloproliferative neoplasms. Conversely, the prevalence of blood type AB in myeloid neoplasms was notably lower than in the control group.ConclusionThe study suggests a potential association between ABO blood types and the risk of developing hematological myeloid neoplasms in adolescents and adults. Further research is warranted to elucidate the underlying mechanisms of this relationship.

Abstract Formation of exotic topological states on technologically important semiconductor substrate is significant from the aspects of both fundamental research and practical implementation. Here, we demonstrate one-dimensional (1D) topological phase and tunable soliton states in atomic nanolines self-assembled on Si(001) surface. By first-principles calculations and tight-binding modeling, we reveal that Bi nanolines provide an ideal system to realize a multi-orbital Su–Schrieffer–Heeger (SSH) model, and the electronic properties can be modulated by substrate-orbital-filtering effect. The topological features are confirmed by nontrivial end states for a finite-length nanoline and (anti-)soliton states at the boundary of two topologically distinct phases. We demonstrate that solitons are highly mobile on the surface, and their formation could be controlled by surface B/N doping. As these nanolines can extend several micrometers long without kinks, and quantum transport simulations suggest clear signatures of topological states characterized by transmission resonance peaks, our work paves an avenue to achieve 1D topological phase compatible with semiconductor technology and to engineer the properties with high tunability and fidelity for quantum information processing.

Oxidative damage resulting from weaning stress significantly impacts the growth performance and health status of piglets. Taurine, a dietary antioxidant with diverse functions, was investigated in this study for its protective role against weaning stress-induced oxidative damage and its underlying mechanism. Forty 28-day-old male castrated weaned piglets were randomly assigned to four groups. The control group received the basal diet, while the experimental groups were fed the basal diet supplemented with 0.1, 0.2%, or 0.3% taurine over a 28-day period. In vitro, H2O2 was utilized to induce oxidative damage to the jejunal mucosa of piglets via IPEC-J2 cells. The results demonstrated that taurine supplementation reduced the incidence of diarrhea in piglets compared to that in the control group (p

Abstract Introduction Acute leukemia often affects microcirculation perfusion. This study aimed to investigate retinal microvascular changes in patients with acute leukemia without retinopathy during clinical remission using optical coherence tomography angiography (OCTA) and to determine the correlation of these changes with systemic laboratory values. Methods Thirty-eight patients in remission from acute leukemia with no retinopathy (NLR group) and 36 age-matched healthy individuals (control group) were included in this cross-sectional study. OCTA parameters, including the central foveal thickness (CFT), foveal avascular zone (FAZ) area, FAZ perimeter, acircularity index (AI), foveal density (FD300), and the vessel densities (VDs) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris were analyzed in a 6 × 6 mm2 macular scan. Correlation and multiple linear regression analyses were conducted to identify potential systemic characteristics associated with these OCTA metrics. Results AI (P = 0.034) and FD300 (P

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy. Objective We investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis. Methods C57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1–4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK). Results Three doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment. Conclusion Amifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism.

Abstract When the nanoparticles (NPs) in food contact materials are exposed, they may be ingested with the food matrix, resulting in unknown impacts. Here, the biological response of the nanocomposites of nano zinc oxide (nZnO) and walnut protein‐derived peptides (i.e., PW5, WN5, AE6, and WE7) on the Lactobacillus rhamnosus LRa05 growth and adhesion was studied. In an in vitro mouse intestinal adhesion model, we first spotted that the probiotics LRa05 primarily adhered to and colonized the colonic segment. nZnO effectively inhibited the growth and adhesion properties of LRa05 at high concentrations (≥ 1000 μg/mL). Fortunately, when compared to the individual nZnO, the nZnO‐walnut‐derived peptides nanocomposites significantly increased the growth of LRa05. It was found that the alterations in the adhesion ability of LRa05 after treatment with various substances (nZnO and nanocomposites of nZnO‐walnut peptides) were related to the auto‐aggregating property on the LRa05 surface. These results shed light on the effect of food matrices on the safety of nanomaterials in food, and they may have far‐reaching implications for the use of nanomaterials in the food industry.

As the commercialisation of Intelligent Connected Vehicles (ICVs) accelerates, Vehicle-to-Everything (V2X)-based general testing and assessment systems have emerged at the forefront of the research. Current field testing schemes mostly follow the norms of traditional vehicle tests. In contrast, Original Equipment Manufacturers (OEMs) have increasingly focused on the potential influence of V2X communication performance on the application response characteristics. Our previous work resulted in a C-V2X (Cellular-V2X) large-scale testing system (LSTS) for communication performance testing. However, when addressing the need to combine application and communication, the system software faces confronts heightened technical challenges. This paper proposes a layered software architecture for the automated C-V2X LSTS, which is tailored to combined scenarios. This architecture integrates scenario encapsulation technology with a large-scale node array deployment strategy, enabling communication and application testing under diversified scenarios. The experimental results demonstrate the scalability of the system, and a case study of Forward Collision Warning (FCW) validates the effectiveness and reliability of the system.

Weaning stress can trigger diarrhea, cause intestinal damage, and disrupt the intestinal flora of piglets, ultimately resulting in retarded growth or even the death of the animals. Traditional Chinese medicine residues encompass numerous bioactive compounds and essential nutrients; however, their efficient utilization remains a challenge. Consequently, our study sought to explore the impact of traditional Chinese medicine residues, specifically Isatidis Root residue (IRR), on the growth performance, intestinal function, and occurrence of weaning diarrhea in newly weaned piglets. Forty healthy, castrated Duroc × Landrace × Yorkshire males, weaned at 21 days old and exhibiting similar body conditions, were randomly allocated into five groups, with eight piglets in each group. The results indicated that the dietary inclusion of IRR at concentrations ranging from 0.5% to 4.0% notably decreased the incidence of diarrhea in weaned piglets compared to the control group (p < 0.05). Serum LDL-C and globulin (GLB) contents were reduced in response to dietary IRR concentrations (0.5% to 4.0%), while serum albumin (ALB) and albumin/globulin (A/G) contents were enhanced (p < 0.05). Dietary 0.5%, 1.0%, and 2.0% IRR resulted in significant increases in villus height (VH) and villus height/crypt depth (V/C) ratios in the jejunum, V/C ratios in the ileum, and the number of villi goblet cells both in the jejunum and ileum. IRR also led to a significant decrease in the crypt depth (CD) of the jejunum and ileum (p < 0.05). Furthermore, the expression of IL-6 in the jejunum was significantly increased in IRR-fed piglets (0.5% to 4.0%) (p < 0.05). IRR demonstrated inhibitory effects on harmful bacteria in the gastrointestinal microbiome, including Campylobacter, Actinobacillus minor, and Ralstonia pickettii, indicating its broad-spectrum bacteriostatic properties. In conclusion, dietary IRR alleviated diarrhea in weaned piglets and improved gut function and microbial compositions.

Abstract Flavonoids are widely distributed in nature and have a variety of beneficial biological effects, including antioxidant, anti‐inflammatory, and anti‐obesity effects. All of these are related to gut microbiota, and flavonoids also serve as a bridge between the host and gut microbiota. Flavonoids are commonly used to modify the composition of the gut microbiota by promoting or inhibiting specific microbial species within the gut, as well as modifying their metabolites. In turn, the gut microbiota extensively metabolizes flavonoids. Hence, this reciprocal relationship between flavonoids and the gut microbiota may play a crucial role in maintaining the balance and functionality of the metabolism system. In this review, we mainly highlighted the biological effects of antioxidant, anti‐inflammatory and antiobesity, and discussed the interaction between flavonoids, gut microbiota and lipid metabolism, and elaborated the potential mechanisms on host lipid metabolism.

Low viability of seed cells and the concern about biosafety restrict the application of cell-based tissue-engineered bone (TEB). Exosomes that bear similar bioactivities to donor cells display strong stability and low immunogenicity. Human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-Exos) show therapeutic efficacy in various diseases. However, little is known whether hUCMSCs-Exos can be used to construct TEB to repair bone defects. Herein, PM-Exos and OM-Exos were separately harvested from hUCMSCs which were cultured in proliferation medium (PM) or osteogenic induction medium (OM). A series of in-vitro studies were performed to evaluate the bioactivities of human bone marrow mesenchymal stem cells (hBMSCs) when co-cultured with PM-Exos or OM-Exos. Differential microRNAs (miRNAs) between PM-Exos and OM-Exos were sequenced and analyzed. Furthermore, PM-Exos and OM-Exos were incorporated in 3D printed tricalcium phosphate scaffolds to build TEBs for the repair of critical-sized calvarial bone defects in rats. Results showed that PM-Exos and OM-Exos bore similar morphology and size. They expressed representative surface markers of exosomes and could be internalized by hBMSCs to promote cellular migration and proliferation. OM-Exos outweighed PM-Exos in accelerating the osteogenic differentiation of hBMSCs, which might be attributed to the differentially expressed miRNAs. Furthermore, OM-Exos sustainably released from the scaffolds, and the resultant TEB showed a better reparative outcome than that of the PM-Exos group. Our study found that exosomes isolated from osteogenically committed hUCMSCs prominently facilitated the osteogenic differentiation of hBMSCs. TEB grafts functionalized by OM-Exos bear a promising application potential for the repair of large bone defects.

Gastric cancer is one of the cancers with increasing incidence and ranks fourth globally among the most frequent causes of cancer-related mortality. Early gastric cancer is often asymptomatic or presents with atypical symptoms, and the majority of patients present with advanced disease upon diagnosis. Brain metastases are present in approximately 1% of gastric cancer patients at the time of diagnosis, which significantly contributed to the overall mortality of the disease worldwide. Conventional therapies for patients with brain metastases remain limited and the median overall survival of patients is only 8 months in advanced cases. Recent studies have improved our understanding of the molecular mechanisms underlying gastric cancer brain metastases, and immunotherapy has become an important treatment option in combination with radiotherapy, chemotherapy, targeted therapy and surgery. This review aims to provide insight into the cellular processes involved in gastric cancer brain metastases, discuss diagnostic approaches, evaluate the integration of immune checkpoint inhibitors into treatment and prognosis, and explore the predictive value of biomarkers in immunotherapy.

Abstract Background Compared to that of bacteria, the role of gut fungi in obesity development remains unknown. Results Here, alterations in gut fungal biodiversity and composition were confirmed in obese pig models and high-fat diet (HFD)-fed mice. Antifungal drugs improved diet-induced obesity, while fungal reconstruction by cohousing or fecal microbiota transplantation maintained the obese phenotype in HFD-fed mice. Fungal profiling identified 5 fungal species associated with obesity. Specifically, Ascomycota_sp. and Microascaceae_sp. were reduced in obese mice and negatively correlated with fat content. Oral supplementation with fungi was sufficient to prevent and treat diet-induced obesity. Clec7a, which is involved in fungal recognition, was highly expressed in HFD-fed mice. The Clec7a agonist accelerated diet-induced obesity, while Clec7a deficieny in mice resulted in resistance to diet-induced obesity and blocked the anti-obese effect of antifungal drugs and fungi. Conclusions Taken together, these results indicate that gut fungi/Clec7a signaling is involved in diet-induced obesity and may have therapeutic implications as a biomarker for metabolic dysregulation in humans. Video Abstract

Abstract Background Liver metastasis is one of the most important reasons for high mortality of colorectal cancer (CRC). Growing evidence illustrates that lncRNAs play a critical role in CRC liver metastasis. Here we described a novel function and mechanisms of BACE1-AS promoting CRC liver metastasis. Methods qRT-PCR and in situ hybridization were performed to examine the BACE1-AS level in CRC. IGF2BP2 binding to m6A motifs in BACE1-AS was determined by RIP assay and S1m-tagged immunoprecipitation. Transwell assay and liver metastasis mice model experiments were performed to examine the metastasis capabilities of BACE1-AS knockout cells. Stemness-like properties was examined by tumor sphere assay and the expression of stemness biomarkers. Microarray data were acquired to analyze the signaling pathways involved in BACE1-AS promoting CRC metastasis. Results BACE1-AS is the most up-regulated in metastatic CRC associated with unfavorable prognosis. Sequence blast revealed two m6A motifs in BACE1-AS. IGF2BP2 binding to these two m6A motifs is required for BACE1-AS boost in metastatic CRC. m6A modified BACE1-AS drives CRC cells migration and invasion and liver metastasis both in vitro and in vivo. Moreover, BACE1-AS maintains the stemness-like properties of CRC cells. Mechanically, BACE1-AS promoted TUFT1 expression by ceRNA network through miR-214-3p. CRC patients with such ceRNA network suffer poorer prognosis than ceRNA-negative patients. Depletion of TUFT1 mimics BACE1-AS loss. BACE1-AS activated Wnt signaling pathway in a TUFT1 dependent manner. BACE1-AS/miR-214-3p/TUFT1/Wnt signaling regulatory axis is essential for CRC liver metastasis. Pharmacologic inhibition of Wnt signaling pathway repressed liver metastasis and stemness-like features in BACE1-AS over-expressed CRC cells. Conclusion Our study demonstrated BACE1-AS as a novel target of IGF2BP2 through m6A modification. m6A modified BACE1-AS promotes CRC liver metastasis through TUFT1 dependent activation of Wnt signaling pathway. Thus, targeting BACE1-AS and its downstream Wnt signaling pathways may provide a new opportunity for metastatic CRC intervention and treatment.

The presence of free gossypol (FG) in cottonseed meal (CSM) greatly limits the use of CSM as a high-quality protein feed. Microbial fermentation is an effective method to simultaneously reduce FG and improve the nutritional value of CSM. In this study, using potato dextrose agar containing acetic gossypol as a selective medium and humus soil from cotton fields as the source, we isolated six strains of fungi capable of tolerating FG. With an inoculation ratio of 8% (8 mL × 106 CFU/mL cells or spores in 100 g fermented CSM), 50% moisture content, and a temperature of 30 °C, CSM was fermented for 5 days. The results showed that strain F had the highest FG removal rate at 56.43%, which was identified as Rhodotorula mucilaginosa (R. mucilaginosa) and named R. mucilaginosa TG529. Further optimization revealed that when the fermentation time was extended to 11 days, TG529 achieved a maximum FG removal rate of 73.29%. Compared to the original sample, treatment with TG529 significantly increased the contents of crude protein, acid-soluble protein, and 18 amino acids, while significantly reducing the contents of crude fiber, neutral detergent fiber (NDF), and acid detergent fiber in fermented cottonseed meal (FCSM). Using atmospheric and room temperature plasma for mutagenesis of TG529, it was found that the mutated TG529 significantly increased the contents of acid-soluble protein and phenylalanine in FCSM, significantly reduced the NDF content, and enhanced the FG removal rate to 76.50%. In summary, this study screened and mutagenized a strain of FG detoxifying fungus, R. mucilagnosa TG529, which can effectively reduce the FG content and improve the nutritional value of CSM by solid-state fermentation.

Objective: Gestational diabetes mellitus (GDM) affects 7% of pregnant women worldwide. How to effectively treat GDM has always been a concern of people.Research methods: In this study, a diabetes model was established by drug-induced mice. Subsequently, the blood glucose levels and serum insulin changes of the mice after N-acetyl-l-cysteine (NAC) treatment were observed. At the same time, the effect of NAC on reproduction of GDM mice was recorded.Results of the study: Mice fed NAC showed significantly improved glucose tolerance and insulin sensitivity compared to Diabetic/Control. Total serum cholesterol, serum triglycerides, and serum low-density lipoprotein were significantly reduced, and atherosclerosis index was much lower than in control mice. In addition, Diabetic/Control mice had lower litter sizes and higher birth weights. NAC treatment significantly restored litter size and reduced birth weight in Diabetic/Control mice. It was found in WB assay that the NAC-fed group significantly increased nuclear Nrf2 and HO-1 expression levels.Conclusion: NAC can improve blood glucose tolerance in GDM mice; NAC effectively relieves the symptoms of hyperlipidemia caused by GDM; NAC enhances the expression of Nrf2/HO-1 in the liver, thereby restoring redox homeostasis. NAC can reduce gestational diabetes-related disease indicators by oral administration, and has a beneficial effect on the offspring of pregnant mice (reduces its diabetes disease indicators).

With the greatly increased penetration rate of wind power, photovoltaic, and other new energy sources in the power system, the proportion of controllable units gradually decreased, resulting in increased system uncertainty. The biogas power generation system can effectively alleviate the pressure caused by source-load uncertainty in such high-permeability systems of new energy sources such as wind power and photovoltaic. Hence, from the perspective of the power system, this paper introduces a capacity demand analysis method for a rural biogas power generation system capable of independent operation amidst source-load uncertainty. To enhance the depiction of pure load demand uncertainty, a scene set generation method is proposed, leveraging quantile regression analysis and Gaussian mixture model clustering. Each scene’s data and probability of occurrence elucidate the uncertainty of pure load demand. An integrated optimal operation model for new energy and biogas-generating units, free from energy storage capacity constraints, is established based on the generated scenario set. Addressing considerations such as biogas utilization rate and system operation cost, a biogas storage correction model, utilizing the gas storage deviation degree index and the cost growth rate index, is developed to determine biogas demand and capacity. The example results demonstrate the significant reduction in gas storage construction costs and charging and discharging imbalances achieved by the proposed model while ensuring systemic operational cost effectiveness.

Based on an improved genetic algorithm and debris flow disaster monitoring network, this study examines the monitoring and early warning method of debris flow expansion behavior, divides the risk of debris flow disaster, and provides a scientific basis for emergency rescue and post-disaster recovery. The function of the debris flow disaster monitoring network of the spreading behavior disaster chain is constructed. According to the causal reasoning of debris flow disaster monitoring information, the influence factors of debris flow, such as rainfall intensity and duration, are selected as the inputs of the Bayesian network, and the probability of a debris flow disaster is obtained. The probability is compared with the historical data threshold to complete the monitoring and early warning of debris flow spreading behavior. Innovatively, by introducing niche technology to improve traditional genetic algorithms by learning Bayesian networks, the optimization efficiency and convergence speed of genetic algorithms are improved, and the robustness of debris flow monitoring and warning is enhanced. The experimental results show that this method divides debris flow disasters into the following five categories based on their danger: low-risk area, medium-risk area, high-risk area, higher-risk area, and Very high-risk area. It accurately monitors the expansion of debris flows and completes early warning. The disaster management department can develop emergency rescue and post-disaster recovery strategies based on early warning results, thus providing a scientific basis for debris flow disasters. The improved genetic algorithm has a higher learning efficiency, a higher accuracy, a faster convergence speed, and higher advantages in learning time and accuracy of the Bayesian network structure.

Weaning stress can induce diarrhea, intestinal damage and flora disorder of piglets, leading to slow growth and even death of piglets. Traditional Chinese medicine residue contains a variety of active ingredients and nutrients, and its resource utilization has always been a headache. Therefore, we aimed to investigate the effects of traditional Chinese medicine residues (Xiasangju, composed of prunellae spica, mulberry leaves, and chrysanthemum indici flos) on growth performance, diarrhea, immune function, and intestinal health in weaned piglets. Forty-eight healthy Duroc× Landrace × Yorkshire castrated males weaned aged 21 days with similar body conditions were randomly divided into 6 groups with eight replicates of one piglet. The control group was fed a basal diet, the antibiotic control group was supplemented with 75 mg/kg chlortetracycline, and the residue treatment groups were supplemented with 0.5%, 1.0%, 2.0% and 4.0% Xiasangju residues. The results showed that dietary Xiasangju residues significantly reduced the average daily feed intake, but reduced the diarrhea score (P < 0.05). The 1.0% and 2.0% Xiasangju residues significantly increased the serum IgM content of piglets, and the 0.5%, 1.0%, 2.0% and 4.0% Xiasangju residues significantly increased the serum IgG content, while the 1.0%, 2.0% and 4.0% Xiasangju residues significantly increased the sIgA content of ileal contents (P < 0.05). Dietary Xiasangju residues significantly increased the villus height and the number of villus goblet cells in the jejunum and ileum, and significantly decreased the crypt depth (P

Acute myeloid leukemia (AML) is a blood cancer that is diverse in terms of its molecular abnormalities and clinical outcomes. Iron homeostasis and cell death pathways play crucial roles in cancer pathogenesis, including AML. The objective of this study was to examine the clinical significance of genes involved in iron-related cell death and apoptotic pathways in AML, with the intention of providing insights that could have prognostic implications and facilitate the development of targeted therapeutic interventions. Gene expression profiles, clinical information, and molecular alterations were integrated from multiple datasets, including TCGA-LAML and GSE71014. Our analysis identified specific molecular subtypes of acute myeloid leukemia (AML) displaying varying outcomes, patterns of immune cell infiltration, and profiles of drug sensitivity for targeted therapies based on the expression of genes involved in iron-related apoptotic and cell death pathways. We further developed a risk model based on four genes, which demonstrated promising prognostic value in both the training and validation cohorts, indicating the potential of this model for clinical decision-making and risk stratification in AML. Subsequently, Western blot analysis showed that the expression levels of C-Myc and CyclinD1 were significantly reduced after CD4 expression levels were knocked down. The findings underscore the potential of iron-related cell death pathways as prognostic biomarkers and therapeutic targets in AML, paving the way for further research aimed at understanding the molecular mechanisms underlying the correlation between iron balance, apoptosis regulation, and immune modulation in the bone marrow microenvironment.

Background: Co-stimulatory molecules have been shown to enhance antitumor immune responses, but their role in Diffuse Large B-cell Lymphoma (DLBCL) remains unexplored. Methods: This study aimed to explore the molecular typing of DLBCL with co-stimulatory molecule genes and to construct a prognostic profile to improve treatment decisions and clinical outcomes. Results: We conducted the first comprehensive analysis of co-stimulatory molecules in DLBCL patients and identified five co-stimulatory molecule genes with prognostic and diagnostic values. Consensus cluster analysis based on these five co-stimulatory molecule genes revealed that the two identified clusters had different distribution patterns and prognostic differences. Co-stimulatory molecular correlation signatures were then constructed based on these five co-stimulatory molecular genes and validated in an external dataset, showing good performance in predicting patient prognosis. The signature is an independent risk factor for DLBCL patients and significantly correlates with clinical factors in patients and can be used as a complement to clinical factors. Furthermore, the signature was associated with the tumor immune microenvironment. Patients identified as being at high risk according to our signature exhibit high levels of immune cell infiltration microenvironment. Conclusions: In conclusion, our signature can provide clinicians with prognostic predictions and help guide the treatment of patients with DLBCL.

Cellular Vehicle-to-everything (V2X) is evolving from a communication technology for safety messages towards a platform for advanced V2X services such as platooning and autonomous driving. The development of technical specifications for V2X communications is done across several task specification groups (TSGs) and working groups (WGs) within 3rd Generation Partnership Project (3GPP). In this paper, we focus on radio access network (RAN) aspects for direct communication between user equipments (UEs), which is known as sidelink (SL) communication. Resource allocation for SL communication can be performed in one of two modes. In the first mode, resource allocation is centralized in the network. In the second mode, resource allocation is performed in a distributed manner among UEs, where resource selection is performed at a transmitting UE, i.e., the transmitting UE determines time and frequency resources for a SL transmission without the assistance of a base station. In this paper, we review V2X evolution from 4G to 5G in 3GPP focusing on resource allocation aspects defined in Long-Term Evolution (LTE) and New Radio (NR) specifications, with particular attention given to the difference in design and performance of each. We highlight the key 3GPP standard developments on V2X resource allocation which includes enhanced resource reselection mechanisms and partial sensing schemes. It is observed that NR V2X resource reselection mechanism can provide up to 20% of reliability improvement over LTE V2X and NR V2X partial sensing scheme can provide up to 95% of reduced power consumption over full sensing scheme.

Abstract Background With increasing incidence and mortality, colorectal cancer (CRC) seriously endangers human health. LARP6, a member of La-related protein (LARP) family, is a RNA binding protein and probably associates with CRC progression, but its specific roles and mechanisms in CRC still remain unknown. Method Quantitative real-time PCR (qPCR), western blot, and immunohistochemistry were employed to examine LARP6 expression in CRC tissues. Using the stable LARP6 overexpression or interference CRC cell lines, the effect of LARP6 on CRC progression were evaluated. High-throughput RNA immunoprecipitation sequencing (RIP-seq) and a series of relevant experiments were conducted to explain how LARP6 functions. SPSS software was used for statistical analysis. Result In this study, we found that LARP6 expression is downregulated in CRC and correlates with patients’ overall survival and relapse-free survival. Furthermore, altered LARP6 expression influences CRC cells invasion and metastasis. Mechanically, we discovered that LARP6 bind ZNF267 mRNA and regulated its stability and translation. LARP6 inhibited expression of SGMS2, a downstream target of ZNF267, resulting in ceramide and sphingomyelin imbalance in CRC cells. Interestingly, LARP6 also enhances autophagy activity of CRC cells, and the effect was at least partially determined by the inhibition of SGMS2-mediated sphingomyelin synthesis. Conclusion Our study showed how LARP6/ZNF267/SGMS2 axis influence CRC progression, which contributes to further understanding of the molecular mechanisms underlying CRC development.

Abstract Background and rationale Idiopathic pulmonary fibrosis is a critical disease with a poor prognosis. Although different studies have been conducted for the treatment of idiopathic pulmonary fibrosis, limited treatments are available. Jin-shui Huan-xian granule (JHG), which is a Chinese medicine herbal compound, has shown promising efficacy in reducing frequencies of acute exacerbations, improving exercise capacity the quality of life of patients with idiopathic pulmonary fibrosis. This study is to evaluate the efficacy and safety of JHG for IPF. Subjects and methods This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 312 idiopathic pulmonary fibrosis patients will be enrolled and randomly allocated to one of the two groups with 1:1. After a 2-week washout period, 52-week treatment will also be performed for all the patients. Patients in the experimental group and the control group will be given JHG and JHG placebo, respectively. Outcome measures including acute exacerbations, pulmonary function, dyspnea, exercise capacity, and quality of life will be evaluated in this study. Discussion Based on our previous study, it is hypothesized that JHG will reduce acute exacerbations; improve exercise capacity, pulmonary function, and quality of life; and delay the disease progression-free. High-level evidence-based support for TCM in IPF will also be obtained in this study. Trial registration ClinicalTrials.gov NCT04187690. Register on December 11, 2019

Summary: Lead halide perovskites are prospective candidates for CO2 photoconversion. Herein, we report copper-doped lead-free Cs2AgSbCl6 double perovskite microcrystals (MCs) for gas-solid phase photocatalytic CO2 reduction. The 0.2Cu@Cs2AgSbCl6 double perovskite MCs display unprecedented CO2 photoreduction capability with CO and CH4 yields of 412 and 128 μmol g−1, respectively. The ultrafast transient absorption spectroscopy reveals the enhanced separation of photoexcited carriers in copper-doped Cs2AgSbCl6 MCs. The active sites and reaction intermediates on the surface of the doped Cs2AgSbCl6 are dynamically monitored and precisely unraveled based on the in-situ Fourier transform infrared spectroscopy investigation. In combination with density functional theory calculations, it is revealed that the copper-doped Cs2AgSbCl6 MCs facilitate sturdy CO2 adsorption and activation and strikingly enhance the photocatalytic performance. This work offers an in-depth interpretation of the photocatalytic mechanism of Cs2AgSbCl6 doped with copper, which may provide guidance for future design of high-performance photocatalysts for solar fuel production.

Two-dimensional Bi grown on semiconductor substrate, a large-gap quantum spin Hall insulator characterized by a ( p _x , p _y )-orbital hexagonal lattice, has been theoretically proposed and experimentally confirmed. Here, by combining tight-binding modeling with first-principles calculations, we investigate the electronic structures and quantum transport properties of Bi nanoribbons (NRs), focusing on the topological edge states for nanoelectronics. We reveal that band gap emerges due to the quantum confinement, and the gaps size depends crucially on the width and edge shape: for zigzag NRs, the gap decreases monotonically with the increase of width; while for armchair NRs, it can be categorized into three subgroups with band-gap hierarchies of $E_ {\mathrm{g}(3p-1)} \gt E_ {\mathrm{g}(3p)} \gt E_ {\mathrm{g}(3p+1)}$ , so that the overall relation is an oscillating dependence dumped by 1/width decay. Quantum transport calculations demonstrate that the conductance is quantized to 2 $\mathrm{e}^{2}/h$ , and an applied gate voltage can efficiently regulate the conductance plateau, originating from the interplay between gate voltage and topological gaps. Furthermore, the quantized conductance remains robust against strong disorder, suggesting the unique advantage of topological states for electronic transport. This work not only provides fundamental insights into the electronic properties of topological insulator nanostructures, but also sheds light on the potential applications of exotic states for quantum devices compatible with semiconductor technology.

Environmental pollution often occurs in the process of mining, beneficiation and smelting of metal mines.Arsenic pollution caused by acid mine drainage (AMD) is one of the most serious pollution problems of heavy metals. At present, the understanding of the evolution process of secondary minerals is insufficient. This paper summarizes the occurrence form of arsenic in metal sulfide.The specific chemical process of activation and migration in different minerals are discussed.Three rules of form transformation are concluded. ①Pyrite and arsenopyrite are the most common arsenic-bearing minerals in metal sulfide mines; ②Arsenic is activated by the oxidation and dissolution of primary minerals, existing mainly in the form of arsenate and arsenite in AMD of which arsenite is more migratory. ③Adsorptive precipitation of secondary minerals in AMD (such as ferro-vanadium, goethite, scallion, etc.) can slow the migration rate and reduce the migration amount of arsenic but cannot prevent the migration process. The migration mechanism of arsenic in the mine environment is reviewed, and new treatment schemes and research directions are proposed.

Gastric cancer (GC) is a prevalent malignant tumor of the digestive system worldwide, ranking among the top five in terms of incidence and mortality. However, the clinical efficacy of conventional treatments for gastric cancer remains limited, with a median overall survival of approximately eight months for advanced cases. In recent years, researchers have increasingly focused on antibody-drug conjugates (ADCs) as a promising approach. ADCs are potent chemical drugs that selectively target cancer cells by binding to specific cell surface receptors with antibodies. Notably, ADCs have demonstrated promising results in clinical studies and have made significant strides in the treatment of gastric cancer. Currently, several ADCs are under investigation in clinical trials for gastric cancer patients, targeting various receptors such as EGFR, HER-2, HER-3, CLDN18.2, Mucin 1, among others. This review offers a comprehensive exploration of ADC drug characteristics and provides an overview of the research progress in ADC-based therapies for gastric cancer.

Summary: Chemiresistive gas sensors generally surfer from low selectivity, inferior anti-humidity, low response signal or signal-to-noise ratio, severely limiting the precise detection of chemical agents. Herein, we exploit high-performance gas sensors based on topological insulator Bi2Se3 that is distinguished from conventional materials by robust metallic surface states protected by time-reversal symmetry. In the presence of Se vacancies, Bi2Se3 nanosheets exhibit excellent gas sensing capability toward NO2, with a high response of 93% for 50 ppm and an ultralow theoretical limit of detection concentration about 0.06 ppb at room temperature. Remarkably, Bi2Se3 demonstrates ultrahigh anti-humidity interference characteristics, as the response with standard deviation of only 3.63% can be achieved in relative humidity range of 0–80%. These findings are supported by first-principles calculations, with analyses on adsorption energy and charge transfer directly revealing the anti-humidity and selectivity. This work may pave the way for implementation of exotic quantum states for intelligent applications.

Abstract Aqueous zinc metal batteries are noted for their cost-effectiveness, safety and environmental friendliness. However, the water-induced notorious issues such as continuous electrolyte decomposition and uneven Zn electrochemical deposition remarkably restrict the development of the long-life zinc metal batteries. In this study, zwitterionic sulfobetaine is introduced to copolymerize with acrylamide in zinc perchlorate (Zn(ClO4)2) solution. The designed gel framework with hydrophilic and charged groups can firmly anchor water molecules and construct ion migration channels to accelerate ion transport. The in situ generated hybrid interface, which is composed of the organic functionalized outer layer and inorganic Cl− containing inner layer, can synergically lower the mass transfer overpotential, reduce water-related side reactions and lead to uniform Zn deposition. Such a novel electrolyte configuration enables Zn//Zn cells with an ultra-long cycling life of over 3000 h and a low polarization potential (~ 0.03 V) and Zn//Cu cells with high Coulombic efficiency of 99.18% for 1000 cycles. Full cells matched with MnO2 cathodes delivered laudable cycling stability and impressive shelving ability. Besides, the flexible quasi-solid-state batteries which are equipped with the anti-vandalism ability (such as cutting, hammering and soaking) can successfully power the LED simultaneously. Such a safe, processable and durable hydrogel promises significant application potential for long-life flexible electronic devices.

Safe, inexpensive aqueous zinc-ion batteries (AZIBs) are regarded as promising energy storage devices. However, they still face issues, including dissolution and collapse of the cathode as well as H2 evolution and the growth of Zn dendrites on the Zn anode. Herein, we simultaneously regulate the cations and anions in the electrolyte for high-capacity, high-stability aqueous zinc–vanadium (Zn–V) batteries based on a bimetallic cation-doped Na0.33K0.1V2O5⋅nH2O cathode. We demonstrate that Na+ ​cations suppress cathode dissolution and restrain Zn dendrite growth on the anode via an electrostatic shield effect. We also illustrate that ClO4− anions participate in energy storage at the cathode and are reduced to Cl−, generating a protective layer on the Zn anode surface and providing a stable interface to decrease Zn dendrites and H2 evolution during long-term cycling. When Na+ and ClO4− are introduced into an aqueous ZnSO4 electrolyte, a Zn/Zn symmetric cell shows durable and reversible Zn stripping/plating for 1500 ​h at a current density of 1 ​mA ​cm−2 and with an area capacity of 1 mAh cm−2. Zn/Na0.33K0.1V2O5⋅nH2O full batteries exhibit a high capacity of 600 mAh g−1 at 0.1 ​A ​g−1 and long-term cycling performance for 5000 cycles, with a capacity of 200 mAh g−1 at 20 ​A ​g−1.

Abstract Background Acute myeloid leukemia (AML) is a genetically heterogeneous blood disorder. AML patients are associated with a relatively poor overall survival. The objective of this study was to establish a machine learning model to accurately perform the prognosis prediction in AML patients. Methods We first screened for prognosis-related genes using Kaplan–Meier survival analysis in The Cancer Genome Atlas dataset and validated the results in the Oregon Health & Science University dataset. With a random forest model, we built a prognostic risk score using patient’s age, TP53 mutation, ELN classification and normalized 197 gene expression as predictor variable. Gene set enrichment analysis was implemented to determine the dysregulated gene sets between the high-risk and low-risk groups. Similarity Network Fusion (SNF)-based integrative clustering was performed to identify subgroups of AML patients with different clinical features. Results The random forest model was deemed the best model (area under curve value, 0.75). The random forest-derived risk score exhibited significant association with shorter overall survival in AML patients. The gene sets of pantothenate and coa biosynthesis, glycerolipid metabolism, biosynthesis of unsaturated fatty acids were significantly enriched in phenotype high risk score. SNF-based integrative clustering indicated three distinct subsets of AML patients in the TCGA cohort. The cluster3 AML patients were characterized by older age, higher risk score, more frequent TP53 mutations, higher cytogenetics risk, shorter overall survival. Conclusions The random forest-based risk score offers an effective method to perform prognosis prediction for AML patients.

Abstract RSL1D1 (ribosomal L1 domain containing 1), a member of the universal ribosomal protein uL1 family, was suggested to be a new candidate target for colorectal cancer (CRC). However, the role of RSL1D1 in cancer, including CRC, remains largely elusive. Here, we demonstrated that RSL1D1 expression was significantly elevated in tumors from CRC patients and that high expression of RSL1D1 was correlated with poorer survival of CRC patients. Functionally, RSL1D1 promoted the proliferation, invasion, and metastasis of CRC cells by suppressing autophagy. Interestingly, RSL1D1 interacted with RAN and inhibited its deacetylation by competitively binding with Sirt7. By affecting the acetylation of RAN, RSL1D1 inhibited the accumulation of nuclear STAT3 and the STAT3-regulated autophagic program. Taken together, our study uncovered the key role of the RSL1D1/RAN/STAT3 regulatory axis in autophagy and tumor progression in CRC, providing a new candidate target for CRC treatment.

Ammonium affects plant root development through different mechanisms than nitrate. Here, the authors show that the Arabidopsis cell wall-localized ferroxidase LPR2 is required to attenuate root growth in response to ammonium.

BackgroundGut microbiota characteristics in patients with diffuse large B-cell lymphoma (DLBCL) are reportedly different when compared with the healthy population and it remains unclear if the gut microbiota affects host immunity and clinical disease features. This research investigated the gut microbiota in patients with untreated DLBCL and analyzed its correlation with patient clinical characteristics, humoral, and cell immune status.MethodsThirty-five patients with untreated DLBCL and 20 healthy controls (HCs) were recruited to this study and microbiota differences in stool samples were analyzed by 16S rDNA sequencing. Absolute ratios of immune cell subset counts in peripheral blood were detected by flow cytometry and peripheral blood cytokine levels were detected by enzyme-linked immunosorbent assay. Relationships between changes in patient microbiomes and clinical characteristics, such as clinical stage, international prognostic index (IPI) risk stratification, cell origin, organ involved and treatment responses were investigated and correlations between differential microbiota and host immune indices were analyzed.ResultsThe alpha-diversity index of intestinal microecology in DLBCL patients was not significantly different when compared with HCs (P>0.05), nonetheless beta-diversity was significantly decreased (P=0.001). p_Proteobacteria were dominant in DLBCL, while p_Bacteroidetes abundance was significantly decreased when compared with HCs (P

Microplastics have become pervasive in ambient aquatic ecosystems over the last decade and are currently a serious global scale concern. To evaluate the potential toxic effects of PVC (polyvinyl chloride) microplastics on the immune functions of freshwater fish, this study undertook a conducted chronic 60-day dietary exposure experiment with Cyprinus carpio var. larvae. We exposed the fish to four microplastic treatments of different concentrations (food rationed diets): no-plastic (control), 10%, 20% and 30%. At the end of the experimental period the impacts of microplastics on the histology, biochemistry, ROS (reactive oxygen species) levels and gene transcription of immune organs were investigated. The results revealed that PVC microplastics induced cytoplasmic vacuolation in the liver, damaged villi in the intestine, inflammatory cell infiltration, hemosiderosis and vacuolar degeneration in the spleen, glomeruli tuft shrinkage and aggregation of melanin macrophage cells in the kidney. Moreover, following PVC microplastics exposure, ROS levels in the liver and protein levels of pro-inflammatory cytokines including IL-6, IL-8, and TNFα in the liver and serum were increased. Furthermore, modifications in the activities of non-specific immunoenzyme ACP (Acid phosphatase), AKP (alkaline phosphatase), LZM (lysozyme), and expression levels of a range of immune-related genes were observed. Using various techniques at the histological, biochemical and molecular levels, our findings demonstrated the effects of PVC microplastics on changes and imbalances in the immune status of carp. The results of this study provide basic toxicological data toward elucidating and quantifying the impacts of microplastics immunotoxicity on aquatic organisms.

Exploring the sensitivity of ecosystem service value (ESV) under land use transformation (LUT) is helpful to promote the rational use of regional land, improve the regional ecological environment carrying capacity, and realize the sustainable development of human beings. Using land use data of Jiangjin Chongqing from 2009 to 2019, this study measured the effect of ecological service value under land use transition in Jiangjin, and analyzed the spatiotemporal evolution characteristics of ecosystem service value based on the land use transfer matrix, change contribution rate (ESVab) and Coefficient of improved cross-sensitivity (CICS). The results showed that 1) the total ESV increased year by year, the ESV change of woodland was the largest, followed by water bodies and cultivated land from 2009 to 2019 in Jiangjin; 2) taking the Yangtze River as the boundary, the ESV in the south was higher than that in the north, but the ESV in the north and south of the Yangtze River increased to different degrees; 3) the contribution rate of forest land was the largest, the contribution rate of cultivated land and woodland was highly correlated with topography and slope, and the contribution rate of water bodies had no obvious spatial distribution characteristics from 2009 to 2019; 4) the CICS between cultivated land, woodland and other land types was higher, and mainly in the medium-high ecological sensitive areas, while the conversion between water bodies, built-up land and other land types was mainly in the medium-low ecological sensitive areas; and 5) the ecologically sensitive areas of the conversion between grassland, unused land and other land types were scattered, and the highly ecologically sensitive areas of the conversion between unused land and other land types were mainly distributed in the southern mountainous area of Jiangjin. It aims to provide important guidance for solving the contradiction between humanity and land and regional environmental problems, so as to realize the sustainable development of the region and environment.

Abstract Objectives To investigate the outcome and short-term follow-up of autogenous tooth shell (TS) grafting for bone augmentation in the esthetic zone, as well as stability and esthetics of implant-supported restoration. Materials and methods A total of 8 patients with 11 implants in 11 sites were enrolled in this study. All the horizontal and/or vertical bone defects in the esthetic zone were augmented by tooth shells, which were fixed laterally to the residual bone with osteosynthesis screws. The gap between the shell and residual bone was filled with Bio-Oss® granules. Four months after bone augmentation, dimensionally sufficient dental implants were inserted and implants-supported prostheses were made 3 months later. The esthetic outcome was evaluated by pink esthetic score (PES) and white esthetic score (WES) one year after prosthetic restoration. Horizontal ridge width (HRW) was assessed before and immediately after bone augmentation, as well as 4 and 19 months post-augmentation by radiography. The stability and absorption of TS grafts were evaluated at the 4th and 19th months post-augmentation. Results Though wound dehiscences occurred in 3 cases, secondary healings were obtained after TS modification and irrigation. The other 5 cases went through uneventful healing during the whole observation period. Radiographic examination showed that HRW was 8.01 ± 0.93 mm (median: 7.80, 95% CI 7.38, 8.64) 4 months after TS augmentation, which was statistically different compared to HRW (2.72 ± 1.73 mm) at the baseline. Mean HRW gain was 5.29 ± 2.03 mm (median: 4.60, 95% CI 3.92, 6.66). Three-dimensional bone volume in all the augmented sites was sufficient for dental implants insertion and prosthetic restoration. Follow-up of one year showed stable marginal bone around dental implants. The implant survival rate was 100%. HRW losses were 0.65 ± 0.43 mm (the 4th month) and 1.05 ± 0.54 mm (the 19th month) compared to HRW immediately after augmentation. The PES and WES of final prosthetic restorations were 8.09 ± 0.70 and 8.91 ± 0.54, respectively. Conclusions Autogenous tooth shell grafting is a reliable approach for bone augmentation in the esthetic zone for dental implant treatment, allowing for favorable stability and esthetic outcome of implant-supported prosthesis within the one-year follow-up period.

ObjectiveThis study aimed to investigate multi-trajectories of systolic and diastolic hypertension and assess their association with the risk of coronary heart disease (CHD) in middle-aged and older Chinese adults.MethodsThe study cohort comprised 4,102 individuals aged 40–75 years with records of at least four systolic blood pressure (SBP) and diastolic blood pressure (DBP). A group-based multi-trajectory model was adopted to identify multi-trajectories of systolic and diastolic hypertension, followed by a logistic model to assess the independent associations between these trajectories and CHD risk. The multinomial logistic model was used to evaluate the impact of baseline covariates on trajectory groups.ResultsSix distinct trajectories for systolic and diastolic hypertension were identified which represent distinct stages of hypertension and were characterized as low-stable, low-increasing, medium-decreasing, medium-increasing-decreasing, isolated systolic hypertension phase, and high-decreasing. Compared with the low-stable group, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 2.23 (1.34–3.70) for the medium-increasing-decreasing group and 1.87 (1.12–3.11) for the high-decreasing group after adjustment for baseline covariates. Compared with the low-increasing group, the ORs and 95% CIs were 1.88 (1.06–3.31) for the medium-increasing-decreasing group. Age, gender, drinking, body mass index (BMI), triglyceride (TG), and fasting plasma glucose (FPG) were independent predictors for trajectory groups 4 and 6.ConclusionNovel, clinically defined multi-trajectories of systolic and diastolic hypertension were identified. Middle-aged and older adults with medium-increasing-decreasing or high-decreasing blood pressure trajectories are potentially critical periods for the development of CHD. Preventing adverse changes in hypertension status and reducing the high risk of CHD is necessary for people in distinct trajectory groups.

The purpose of this experiment was to investigate the effects of different starch and protein levels on lipid metabolism and gut microbes in mice of different genders. A total of 160 male mice were randomly assigned to sixteen groups and fed a 4 × 4 Latin square design with dietary protein concentrations of 16, 18, 20, and 22%, and starch concentrations of 50, 52, 54, and 56%, respectively. The results of the study showed that different proportions of starch and protein had obvious effects on the liver index of mice, and there was a significant interaction between starch and protein on the liver index (p = 0.005). Compared with other protein ratio diets, 18% protein diet significantly increased the serum TBA concentration of mice (p < 0.001), and different starch ratio diets had no effect on serum TBA concentration (p = 0.442). It was proved from the results of ileal tissue HE staining that the low protein diet and the low starch diet were more favorable. There was a significant interaction between diets with different starch and protein levels on Bacteroidetes, Firmicutes and Proteobacteria abundance in feces of mice (p < 0.001). Compared with 16 and 18% protein ratio diets, both 20 and 22% protein diets significantly decreased the Parabacteroides and Alistipes abundance in feces of mice (p < 0.05), and 52% starch ratio diet significantly decreased the Parabacteroides and Alistipes abundance than 50% starch ratio diet of mice (p < 0.05). There was a significant interaction between diets with different starch and protein levels on Parabacteroides (p = 0.014) and Alistipes (p = 0.001) abundance in feces of mice. Taken together, our results suggest that a low protein and starch diet can alter lipid metabolism and gut microbes in mice.

Artemisia argyi leaf is a well-known species in traditional Chinese medicine, and its essential oil (AAEO) has been identified to exert various physiological activities. The aim of this study was to investigate the effects of AAEO on lipid metabolism and the potential microbial role in high-fat diet (HFD)-fed mice. A total of 50 male mice were assigned to five groups for feeding with a control diet (Con), a high-fat diet (HFD), and the HFD plus the low (LEO), medium (MEO), and high (HEO) doses of AAEO. The results demonstrated that dietary HFD markedly increased the body weight gain compared with the control mice (p < 0.05), while mice in the HEO group showed a lower body weight compared to the HFD group (p < 0.05). The weight of fatty tissues and serum lipid indexes (TBA, HDL, and LDL levels) were increased in response to dietary HFD, while there was no significant difference in AAEO-treated mice (p < 0.05). The jejunal villus height was dramatically decreased in HFD-fed mice compared with the control mice, while HEO resulted in a dramatically higher villus height than that in the HFD group (p < 0.05). Microbial α-diversity was not changed in this study, but β-diversity indicated that microbial compositions differed in control, HFD, and EO subjects. At the genus level, the relative abundance of Bacteroides was greater (p < 0.05) in the feces of the Con group when compared to the HFD and EO groups. On the contrary, the abundance of Muribaculum was lower in the Con group compared to the HFD and EO groups (p < 0.05). Although the Muribaculum in the EO group was lower than that in the HFD group, there was no statistically notable difference between the HFD and EO groups (p > 0.05). Simultaneously, the relative abundance of Alistipes (p < 0.05) and Rikenella (p < 0.05) was also dramatically higher in the Con group than in the HFD and EO groups. The abundance of norank_f__norank_o__Clostridia_UCG-014 was lower in the HFD or EO group than in the Con group (p < 0.05). In conclusion, the results suggested that HEO could affect body weight and lipid metabolism without gut microbes in ICR mice, and it was beneficial for the structure of the jejunal epithelial tissue.

ObjectiveWe aimed to construct and validate machine learning models for endotracheal tube (ETT) size prediction in pediatric patients.MethodsData of 990 pediatric patients underwent endotracheal intubation were retrospectively collected between November 2019 and October 2021, and separated into cuffed and uncuffed endotracheal tube subgroups. Six machine learning algorithms, including support vector regression (SVR), logistic regression (LR), random forest (RF), gradient boosting tree (GBR), decision tree (DTR) and extreme gradient boosting tree (XGBR), were selected to construct and validate models using ten-fold cross validation in training set. The optimal models were selected, and the performance were compared with traditional predictive formulas and clinicians. Furthermore, additional data of 71 pediatric patients were collected to perform external validation.ResultsThe optimal 7 uncuffed and 5 cuffed variables were screened out by feature selecting. The RF models had the best performance with minimizing prediction error for both uncuffed ETT size (MAE = 0.275 mm and RMSE = 0.349 mm) and cuffed ETT size (MAE = 0.243 mm and RMSE = 0.310 mm). The RF models were also superior in predicting power than formulas in both uncuffed and cuffed ETT size prediction. In addition, the RF models performed slightly better than senior clinicians, while they significantly outperformed junior clinicians. Based on SVR models, we proposed 3 novel linear formulas for uncuffed and cuffed ETT size respectively.ConclusionWe have developed machine learning models with excellent performance in predicting optimal ETT size in both cuffed and uncuffed endotracheal intubation in pediatric patients, which provides powerful decision support for clinicians to select proper ETT size. Novel formulas proposed based on machine learning models also have relatively better predictive performance. These models and formulas can serve as important clinical references for clinicians, especially for performers with rare experience or in remote areas.

Background and objective: Idiopathic pulmonary fibrosis (IPF) is a critical disease, with limited treatments available. Clinical practices show that traditional Chinese medicine (TCM) has certain efficacy. This study was preliminarily to evaluate the efficacy and safety of TCM treatment based on syndrome differentiation in IPF.Methods: A study design of exploratory, multi-centers, randomized, double-blinded, placebo controlled trial has been adopted. A total of 80 IPF patients from four sub-centers were enrolled. All the patients were randomly assigned into TCM group (TCMG) or control group (CG) in 1:1. Patients in TCMG were given CM granules, as patients in CG given with the placebo of CM granule. All the patients received a 26-week treatment. The efficacy was assessed by acute exacerbations (AEs) of IPF, pulmonary function, clinical symptoms, dyspnea scores (mMRC), health-related quality of life (HRQoL), 6-min walk test (6MWT) and all-cause mortality. Safety has also been assessed.Results: A total of 67 patients completed the trial with 35 in TCM group and 32 in control group. Meaningful differences have been observed in mean changes in AEs (−1.56 times; 95% CI, −2.69 to −0.43, p = 0.01), DLco% (5.29; 95% CI, 0.76 to 9.81, p = 0.02), cough scores (−0.38 points; 95% CI, −0.73 to −0.04, p = 0.03), and 6MWT (30.43 m; 95% CI, 2.85 to 58.00, p = 0.03), with no statistical differences in FEV1, FVC, expectoration, chest tightness, Shortness of breath, Fatigue, Cyanosis, mMRC, CAT, SF-36, and SGRQ total scores in 26 weeks after treatment than before treatment. At of the end of follow-up, a total of 10 patients died, including three and seven in the TCM and control group respectively. And the HR (Hazard ratio) for CM granules in all-cause mortality was 0.39 (95% CI, 0.10–1.52). The drug-related adverse events were not observed.Conclusion: CM granules, as compared with placebo, could reduce frequencies of AEs, improve pulmonary function, HRQoL, exercise capacity and symptoms and signs for IPF to some extent with acceptable side-effect.

S-nitrosylation can influence many pathophysiological processes. Here the authors show that the coupling efficiency of GNAI2 with CXCR5 is enhanced by S-nitrosylation of GNAI2, leading to Hippo-YAP dysfunction in endothelium, and plays a role in diabetes-accelerated atherosclerosis.

For thousands of years, sanghuang is distinctive as a general designation for a group of precious and rare Chinese medicinal mushrooms. Numerous investigations have revealed that polysaccharide is one of the important biological active ingredients of sanghuang with various excellent biological activities, including antioxidant, anti-aging, anti-tumor, immunomodulatory, anti-inflammatory, anti-diabetic, hepatoprotective, and anti-microbial functionalities. For the past two decades, preparation, structural characterization, and reliable bioactivities of the polysaccharides from fruiting bodies, cultured mycelia, and fermentation broth of sanghuang have been arousing extensive interest, and particularly, different strains, sources, and isolation protocols might result in obvious discrepancies in structural features and bioactivities. Therefore, this review summarizes the recent reports on preparation strategies, structural features, bioactivities, and structure-activity relationships of sanghuang polysaccharides, which will enrich the knowledge on the values of natural sanghuang polysaccharides and support their further development and utilization as therapeutic agents, vaccines, and functional foods in tonic and clinical treatment.