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Oxidative stress and aging lead to progressive senescence of nucleus pulposus (NP) cells, resulting in intervertebral disc (IVD) degeneration (IVDD). In some cases, degenerative IVD can further cause low back pain (LBP). Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD. However, the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs. Here, we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with quercetin to alleviate IVDD by removing senescent NP cells. The hydrogel exhibited injectability, biodegradability, prominent biocompatibility and responsive release of quercetin under pathological conditions. In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells. In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models, indicating a potential therapeutic approach for ameliorating IVDD and LBP. This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD, providing a new strategy for IVDD treatment.

Abstract In plants, recognition between resistance gene (R) and virus induces a local hypersensitive response (HR), which is accompanied by systemic acquired resistance (SAR). The dominant resistance gene N in tobacco confers resistance to tobacco mosaic virus (TMV) at both locally inoculated tissues and systemically infected tissues. However, the mechanisms underlying HR- and SAR-mediated viral inhibition are not fully revealed. In this study, we find that Nicotiana glutinosa RNA-binding protein (NgRBP) is an RNA silencing suppressor which enhances TMV-triggered HR. Stronger HR could result in stronger local and systemic RNA silencing as well as SAR. Enhanced RNA silencing in the systemically infected leaves induced by the NgRBP gene is compromised by transient expression of NahG. These results indicate that RNA silencing is activated by HR and plays a crucial role in local and systemic virus resistance. Our results reveal a crosstalk between N gene-mediated virus resistance and RNA silencing which would deepen our understanding of the established HR and SAR models.

Abstract Background Assessing the relationships between spatial and temporal structures and functions of plant communities is an effective way to understand the changing dynamics of plant communities in specific environments. In this study, we investigated the response of structural and functional stabilities of plant communities to stocking rate in the desert steppe over a 16-year grazing period as the research background. Methods We used classical statistical methods to investigate the quantitative characteristics of plant communities over time (2014–2019) and space (2017–2019) at four stocking rates (control, CK, 0 sheep·ha–1·month–1; light grazing, LG, 0.15 sheep·ha–1·month–1; moderate grazing, MG, 0.30 sheep·ha–1·month–1; heavy grazing, HG, 0.45 sheep·ha–1·month–1) in the Stipa breviflora desert steppe of Inner Mongolia. We then examined the relationship between structural and functional stability of plant communities. Results On the spatial scale, the structural stability of plant community was the highest in the LG treatment and the lowest in the MG treatment. The functional stability of plant community was the highest in the MG treatment and the lowest in the HG treatment. On the temporal scale, the structural stability of plant community was the highest in the MG treatment and the lowest in the LG treatment. The functional stability of plant community was the highest in the LG treatment and the lowest in the HG treatment. Affected by the stocking rate, the structural stability of plant community fluctuated more widely on the spatial scale and its functional stability varied more widely on the temporal scale. Nonetheless, the functional stability of the plant community is more responsive to the stocking rate. Conclusions Our findings suggest that influenced by the disturbance of stocking rate, the structural stability of plant community is more significant than the functional stability in the desert grassland ecosystem, which lays a solid foundation for the study of ecosystem stability.

Abstract Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients.

Abstract Background Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear. Results In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P

Abstract Objective This study developed and validated a nomogram utilizing clinical and multi-slice spiral computed tomography (MSCT) features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma. Additionally, we assessed the predictive accuracy of Ki-67 expression levels, as determined by our model, in estimating the prognosis of stage IA lung adenocarcinoma. Materials and methods We retrospectively analyzed data from 395 patients with pathologically confirmed stage IA lung adenocarcinoma. A total of 322 patients were divided into training and internal validation groups at a 6:4 ratio, whereas the remaining 73 patients composed the external validation group. According to the pathological results, the patients were classified into high and low Ki-67 labeling index (LI) groups. Clinical and CT features were subjected to statistical analysis. The training group was used to construct a predictive model through logistic regression and to formulate a nomogram. The nomogram’s predictive ability and goodness-of-fit were assessed. Internal and external validations were performed, and clinical utility was evaluated. Finally, the recurrence-free survival (RFS) rates were compared. Results In the training group, sex, age, tumor density type, tumor-lung interface, lobulation, spiculation, pleural indentation, and maximum nodule diameter differed significantly between patients with high and low Ki-67 LI. Multivariate logistic regression analysis revealed that sex, tumor density, and maximum nodule diameter were significantly associated with high Ki-67 expression in stage IA lung adenocarcinoma. The calibration curves closely resembled the standard curves, indicating the excellent discrimination and accuracy of the model. Decision curve analysis revealed favorable clinical utility. Patients with a nomogram-predicted high Ki-67 LI exhibited worse RFS. Conclusion The nomogram utilizing clinical and CT features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma demonstrated excellent performance, clinical utility, and prognostic significance, suggesting that this nomogram is a noninvasive personalized approach for the preoperative prediction of Ki-67 expression.

Here, we describe a new species of Crotalaria L. discovered in Mengla County, Xishuangbanna Dai Autonomous Prefecture, Yunnan, China. The new species, Crotalaria menglaensis S.A.Rather, was confirmed by identifying diagnostic morphological characteristics, performing principal component analyses of phenotypic traits, and phylogenetic analyses based on nuclear ITS and plastid matK sequences. Phylogenetic analyses recovered the two accessions of the new species to be sister to C. bracteata Roxb. ex DC. In turn, these two species formed the sister clade to the two accessions of C. incana L. The morphometric analyses revealed that all three species were distinct, while the analyses of distinctive characters enabled unambiguous distinction of the new species by its growth habit, leaflets, flower structure and pod morphology. In contrast to the two related species, the new species is currently known only from ca. 100 mature individuals. Thus, this species is considered to be critically endangered.

Phages and phage-encoded lytic enzymes are promising antimicrobial agents. In this study, we report the isolation and identification of bacteriophage KP2025 from Klebsiella pneumoniae. Bioinformatics analysis of KP2025 revealed a putative endolysin, LysKP213, containing a T4-like_lys domain. Purified LysKP213 was found to be highly thermostable, retaining approximately 44.4% of its lytic activity after 20 h of incubation at 95°C, and approximately 57.5% residual activity after 30 min at 121°C. Furthermore, when administered in combination with polymyxin B or fused at the N-terminus with the antimicrobial peptide cecropin A (CecA), LysKP213 exhibited increased antibacterial activity against Gram-negative pathogens, including K. pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli, both in vitro and in vivo. These results indicated that LysKP213 is a highly thermostable endolysin that, when combined with or fused with an outer membrane permeabilizer, has enhanced antibacterial activity and is a candidate agent for the control of infections by Gram-negative pathogens.

Although aboveground biodiversity has been extensively studied, the impact of nutrient enrichment on soil microbial populations remains unclear. Soil microorganisms serve as important indicators in shaping soil nutrient cycling processes and are typically sensitive to nutrient additions. For this, we employed a factorial combination design to examine the impact of nutrient additions on the composition and function of soil bacteria in a temperate steppe. Nitrogen addition promoted the growth of copiotrophic bacteria (Proteobacteria, Firmicutes, and Bacteroidota) but inhibited the growth of oligotrophic bacteria (Acidobacteria, Chloroflexi, and Verrucomicrobiota). Phosphorus addition alleviated phosphorus deficiency, resulting in a decrease in the abundance of phoD-harboring bacteria (Actinobacteria and Proteobacteria). Significant enhancement of soil bacterial alpha diversity was observed only in treatments with added phosphorus. Changes in NO3−-N, NH4+-N, available phosphorus, and dissolved organic carbon resulting from nutrient addition may have a greater impact on microbial community structure than changes in soil pH caused by nitrogen addition. Moreover, nutrient addition may indirectly impact microbial ecological function by altering nutrient availability in the soil. In conclusion, our study suggests that soil nutrient availability, particularly available phosphorus, affects soil bacterial communities and potentially regulates the biogeochemical cycles of soil ecosystems.

Abstract Performance evaluation has great potential to encourage government officials to improve their behavior (performance-oriented government behavior, POGB), but it also tends to lead to behaviors that are detrimental to government performance (non-performance-oriented government behavior, NPOGB). The latter behaviors are prevalent in many parts of the world, especially in areas with fiscal federalist characteristics such as China. This study analyzes POGB and NPOGB and employs game theory to develop a theoretical model to explain the causes of NPOGBs in China, exploring how competition among different jurisdictions leads to them. The findings show that (1) POGB is a condition of Pareto optimality in government behavior, but only represents a very small share of all government behaviors. The majority of behaviors can be categorized as NPOGBs. (2) The primary reason continuous and volatile NPOGBs persist is that, from the perspective of local officials operating under the constraints of information scarcity and risk aversion, they are rational choices, and officials have to imitate one another’s behaviors so as not to be defeated in the competition with others.

Abstract Background Hypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) Hydrogels can biodegrade and be used for controlled drug release. (3) Released T1AM can induce hypothermia. (4) This hydrogel has increased medical value given its simple operation and ability to achieve timely treatment. Methods Pol/T hydrogels were prepared by a low-temperature mixing method and characterized. The effect of the Pol/T hydrogel on traumatic brain injury in mice was studied. The degradation of the hydrogel at the body level was observed with a small animal imager. Brain temperature and body temperature were measured by brain thermometer and body thermometer, respectively. The apoptosis of peripheral nerve cells was detected by immunohistochemical staining. The protective effect of the hydrogels on the blood–brain barrier (BBB) after TBI was evaluated by the Evans blue penetration test. The protective effect of hydrogel on brain edema after injury in mice was detected by Magnetic resonance (MR) in small animals. The enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of inflammatory factors. The effects of behavioral tests on the learning ability and exercise ability of mice after injury were evaluated. Results This hydrogel was able to cool the brain to hypothermia for 12 h while maintaining body temperature within the normal range after TBI in mice. More importantly, hypothermia induced by this hydrogel leads to the maintenance of BBB integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI in mice. This cooling method could be developed as a new approach for hypothermia treatment in TBI patients. Conclusion Our study showed that injectable and biodegradable frozen Pol/T hydrogels to induce local hypothermia in TBI mice can be used for the treatment of traumatic brain injury. Graphical Abstract

Abstract The edible fungus industry is one of the pillar industries in the Yunnan–Guizhou Plateau, China. The expansion of the planting scale has led to the release of various mushroom residues, such as mushroom feet, and other wastes, which are not treated adequately, resulting in environmental pollution. This study investigated the ability of black soldier fly (Hermetia illucens L.) larvae (BSFL) to degrade mushroom waste. Moreover, this study analyzed changes in the intestinal bacterial community and gene expression of BSFL after feeding on mushroom waste. Under identical feeding conditions, the remaining amount of mushroom waste in Pleurotus ostreatus treatment group was reduced by 18.66%, whereas that in Flammulina velutipes treatment group was increased by 31.08%. Regarding gut microbial diversity, compared with wheat bran-treated control group, Dysgonomonas, Providencia, Enterococcus, Pseudochrobactrum, Actinomyces, Morganella, Ochrobactrum, Raoultella, and Ignatzschineria were the most abundant bacteria in the midgut of BSFL in F. velutipes treatment group. Furthermore, Dysgonomonas, Campylobacter, Providencia, Ignatzschineria, Actinomyces, Enterococcus, Morganella, Raoultella, and Pseudochrobactrum were the most abundant bacteria in the midgut of BSFL in P. ostreatus treatment group. Compared with wheat bran-treated control group, 501 upregulated and 285 downregulated genes were identified in F. velutipes treatment group, whereas 211 upregulated and 43 downregulated genes were identified in P. ostreatus treatment group. Using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we identified 14 differentially expressed genes (DEGs) related to amino sugar and nucleotide sugar metabolism in F. velutipes treatment group, followed by 12 DEGs related to protein digestion and absorption. Moreover, in P. ostreatus treatment group, two DEGs were detected for fructose and mannose metabolism, and two were noted for fatty acid metabolism. These results indicate that feeding on edible mushroom waste can alter the intestinal microbial community structure of BSFL; moreover, the larval intestine can generate a corresponding feedback. These changes contribute to the degradation of edible mushroom waste by BSFL and provide a reference for treating edible mushroom waste using BSFL.

Abstract Background Adult neurogenesis occurs in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. The neuronal stem cells in these two neurogenic niches respond differently to various physiological and pathological stimuli. Recently, we have found that the decrement of carboxypeptidase E (CPE) with aging impairs the maturation of brain-derived neurotrophic factor (BDNF) and neurogenesis in the SVZ. However, it remains unknown whether these events occur in the hippocampus, and what the role of CPE is in the adult hippocampal neurogenesis in the context of Alzheimer’s disease (AD). Methods In vivo screening was performed to search for miRNA mimics capable of upregulating CPE expression and promoting neurogenesis in both neurogenic niches. Among these, two agomirs were further assessed for their effects on hippocampal neurogenesis in the context of AD. We also explored whether these two agomirs could ameliorate behavioral symptoms and AD pathology in mice, using direct intracerebroventricular injection or by non-invasive intranasal instillation. Results Restoration of CPE expression in the hippocampus improved BDNF maturation and boosted adult hippocampal neurogenesis. By screening the miRNA mimics targeting the 5’UTR region of Cpe gene, we developed two agomirs that were capable of upregulating CPE expression. The two agomirs significantly rescued adult neurogenesis and cognition, showing multiple beneficial effects against the AD-associated pathologies in APP/PS1 mice. Of note, noninvasive approach via intranasal delivery of these agomirs improved the behavioral and neurocognitive functions of APP/PS1 mice. Conclusions CPE may regulate adult hippocampal neurogenesis via the CPE–BDNF–TrkB signaling pathway. This study supports the prospect of developing miRNA agomirs targeting CPE as biopharmaceuticals to counteract aging- and disease-related neurological decline in human brains.

Objectives: The present study aimed to determine the diagnostic value of sonographic signs in patients who have experienced an acute injury of the anterior talofibular ligament (ATFL), and provide diagnostic evidence for improving the classification of ATFL injuries. Methods: We retrospectively analyzed a total of 158 ATFL injuries, confirmed by surgery or magnetic resonance imaging (MRI), in 157 patients (one patient had bilateral ankle injury). A group of senior radiologists, along with two junior radiologists, identified the direct and indirect sonographic signs of ATFL injuries on ultrasound (US) images, and determined the ATFL injury classification. We then compared the diagnostic accuracy of the ATFL injury classifications, as well as the consistency of sonographic sign identification, between the senior radiologist group and the two junior radiologists. The sonographic signs identified by the senior radiologist group were used as the standard by which we analyzed the diagnostic efficacy of each sonographic sign for ATFL injury classification. Results: The diagnostic accuracy for complete ATFL tears was 88.5 % in the senior radiologist group, which was higher than that for the two junior radiologists (72.3 % and 67.7 %). Compared to the senior radiologist group, the consistency between the two junior radiologists in identifying all sonographic signs of ATFL injuries was low (kappa value 80 %. Direct sonographic signs were further combined with indirect sonographic signs to improve the diagnostic specificity and positive predictive value for the diagnosis of ATFL injuries. Conclusions: High-frequency US is the first choice for the diagnosis of ATFL injuries; however, radiologists with different levels of experience may classify ATFL injuries differently. Refined sonographic signs, especially ligament tension, clarity, and continuity, are helpful in the classification and diagnosis of ATFL injuries and provide guidance for the treatment and management of ankle injuries in clinical practice.

As an exogenous pollutant, the microplastics accumulated in soil could alter microbial activity. The use of plastic mulch in greenhouse vegetable planting not only enhances vegetable yield and quality, but also leads to the formation and accumulation of microplastics in the soil over time. It is essential to determine the characteristics of microplastics and microorganisms in soils with varying years of planting is crucial for ensuring vegetable quality and quantity. Therefore, this study investigated the abundance and particle size of microplastics, the concentration of phthalates (PAEs), and the dynamics of soil microbial activity in greenhouse soils with different planting years (5, 10, 15, 20, 25, and 30 years). Results showed that microplastics increased in abundance, particle size, and PAEs concentration as planting years progressed. Specifically, the abundance of microplastics rose from 70.0 ± 8.7 to 224.0 ± 10.4 items/kg, with the proportion of microplastics sized 0–2 mm increasing from 14.02 to 69.11 %, and the total PAEs concentration in the soil escalating from 0.31 to 1.89 mg/kg. Additionally, Bacteroidetes and Actinobacteria levels increased, correlating with organic matter degradation. Metabolic pathway linked to degradation were enriched according to KEGG analysis. Correlation analysis revealed that microplastics notably decreased soil pH, creating an acidic environment that boosted urease activity and the relative abundance of Nitrospirae. This study sheds light on the accumulation characteristics of microplastics and their impact on soil microbial activity following prolonged planting.

Background: Mesangial cell (MC)-mediated immune inflammatory injury is a basic pathological process in glomerulonephritis. However, due to the limited drug accumulation and serious adverse effects, it remains challenging to explore a rational delivery system integrating high efficiency and low toxicity to deliver anti-inflammatory drugs to the glomerular MC region. Results: Salvianolic acid B (SAB)-loaded hybrid membrane biomimetic nanovesicles (SAB@HMVs) were developed by fusing erythrocyte membrane nanovesicles with mesenchymal stem cells biomimetic membrane nanovesicles. SAB@HMVs had a spheroidal structure, low cytotoxicity, particle size of 143.83 ± 1.33 nm and exhibited a high drug loading capacity (7.02 %±0.30 %) along with a good sustained release function. The in vitro anti-inflammatory results revealed that HMVs were effectively taken up by MCs and showed significant anti-inflammatory activity. Furthermore, in vivo pharmacodynamic studies revealed that SAB@HMVs could deliver SAB to kidney tissue and elicit an effective anti-inflammatory response to improve the pathological changes in the glomerular mesangial region, significantly reducing the levels of cytokines and alleviating kidney inflammation. Especially, noteworthy was the observation that SAB@HMVs augmented the renal delivery of SAB, downregulated the gene expression of p38 MAPK and NF-κB, inhibited the levels of MMP9 and TNF-α proteins as well as elevated the level of iκB protein, indicating that the anti-inflammatory mechanism of SAB@HMVs should be based on regulating MAPK and NF-κB signaling pathways. Conclusion: We provided a novel strategy to increase nanovesicles accumulation in MCs with the potential to exert anti-inflammatory regulatory effects in glomerulonephritis. Furthermore, this biomimetic hybrid membrane loaded with pure drugs may offer a functional platform to address multiple clinical needs.

BackgroundWith the remarkable effect of controlling the increase in drug costs by the first batch of National Key Monitoring and Rational Use Drugs (first NKMRUDs), the National Health Commission of the People’s Republic of China releases the second NKMRUDs to further strengthen the reasonable use of drugs. Unfortunately, the second NKMRUDs include some drugs of National Volume-based Procurement and National Essential Medicines, which challenges the management of pharmaceutical affairs on the three kinds of drugs.ObjectiveThe main objective of this study was to investigate the prevalence of the second NKMRUDs and explore their monitoring indicators.MethodsAn adapted WHO methodology for point prevalence surveys was conducted for the second NKMRUDs. For the monitoring indicators, we sought to explore whether the defined daily dose (DDD) and days of therapy (DOT) can be suitable for the second NKMRUDs through comparing differences between DDD and DOT with the prescribed daily dose (PDD).ResultsAmong the 935 included patients, 29.20% of the patients received at least one of the second NKMRUDs. A total of 273 patients were administered with 487 times of the second NKMRUDs. Among them, 162 , 62 , and 49 patients were receiving one, two, and three or more agents, respectively. The most commonly prescribed second NKMRUDs were compound amino acids, budesonide, and ceftazidime. The total DDDs and DOTs of the second NKMRUDs were 3360.68 and 1819.80, respectively, with the PDDs of 1865.26. The deviations (80.17%) of DDDs from PDDs were significantly greater than those (−2.44%) of DOTs.ConclusionThe prevalence of the second NKMRUDs was obtained by using the adapted PPS methodology at a tertiary university hospital. The DOT indicator is found to more accurately reflect actual consumption than the DDD indicator for second NKMRUDs. It is recommended to use the DOT indicator to monitor second NKMRUDs.

Annulus fibrosus (AF) plays a crucial role in the biomechanical loading of intervertebral disc (IVD). AF is difficult to self-heal when the annulus tears develop, because AF has a unique intricate structure and biologic milieu in vivo. Tissue engineering is promising for repairing AF rupture, but construction of suitable mechanical matching devices or scaffolds is still a grand challenge. To deeply know the varied forces involved in the movement of the native annulus is highly beneficial for designing biomimetic scaffolds to recreate the AF function. In this review, we overview six freedom degrees of forces and adhesion strength on AF tissue. Then, we summarize the mechanical modalities to simulate related forces on AF and to assess the characteristics of biomaterials. We finally outline some current advanced techniques to develop mechanically adaptable biomaterials for AF rupture repair.

Abstract Endophytic fungi play an important role in the growth and development of traditional Chinese medicine plants. We isolated a strain of Acrocalymma vagum from the endophytic fungi of the traditional Chinese plants Paris. To accurately identify this endophytic fungal species of interest, we sequenced the mitochondrial genome of A. vagum, which is the first discovered mitochondrial genome in Massarineae. The A. vagum mitochondrial genome consists of a 35,079-bp closed circular DNA molecule containing 36 genes. Then, we compared the general sequence characteristics of A. vagum with those of Pleosporales, and the second structure of the 22 tRNAs was predicted. The phylogenetic relationship of A. vagum was constructed using two different data sets (protein-coding genes and amino acids). The phylogenetic tree shows that A. vagum is located at the root of Pleosporales. The analysis of introns shows that the number of introns increases with the increase in branch length. The results showed that monophyly was confirmed for all families in Pleosporales except for Pleosporaceae. A. vagum is an ancient species in the Pleosporales, and Pleosporaceae may require further revision. In Pleosporales, the number of introns is positively correlated with branch length, providing data for further study on the origin of introns.

Abstract Background The case mix index (CMI) may reflect the severity of disease and the difficulty of care objectively, and is expected to be an ideal indicator for assessing the nursing workload. The purpose of this study was to explore the quantitative relationship between daily nursing worktime (DNW) and CMI to provide a method for the rational allocation of nursing human resources. Methods Two hundred and seventy-one inpatients and 36 nurses of the department of hepatobiliary surgery were prospectively included consecutively from August to September 2022. The DNW of each patient were accurately measured, and the CMI data of each patient were extracted. Among 10 curve estimations, the optimal quantitative model was selected for constructing the nursing human resource allocation model. Finally, the applicability of the allocation model was preliminarily assessed by analyzing the relationship between the relative gap in nursing human resources and patient satisfaction, as well as the incidence of adverse events in 17 clinical departments. Results The median (P25, P75) CMI of the 271 inpatients was 2.62 (0.92, 4.07), which varied by disease type (F = 3028.456, P

AbstractTemozolomide (TMZ) is a conventional chemotherapeutic drug for glioma, however, its clinical application and efficacy is severely restricted by its drug resistance properties. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme, which can repair the DNA damage caused by TMZ. A large number of clinical data show that reducing the expression of MGMT can enhance the chemotherapeutic efficacy of TMZ. Therefore, in order to improve the resistance of glioma to TMZ, an angiopep-2 (A2) modified nanoprodrug of polytemozolomide (P(TMZ)n) that combines with MGMT siRNA (siMGMT) targeting MGMT was developed (A2/T/D/siMGMT). It not only increased the amount of TMZ within tumor lesion site, but also reduced MGMT expression in glioma. The in vitro experiments indicated that the A2/T/D/siMGMT effectively enhanced the cellular uptake of TMZ and siMGMT, and resulted in a significant cell apoptosis and cytotoxicity in the glioma cells. The in vivo experiments showed that glioma growth was inhibited and the survival time of animals were prolonged remarkably after A2/T/D/siMGMT was injected via tail vein. The results showed that the therapeutic effect of A2/T/D/siMGMT in the treatment of glioma was significantly improved.

Suillus is one of the most important genera of ectomycorrhizal fungi. As a model for studying host specificity, its molecular fragments and nuclear genome have been analyzed. However, its mitochondrial genome has not yet been reported. In this study, we assembled five mitogenomes of Suillus and analyzed and compared their basic characteristics. Owing to the large number of introns as well as intergenic regions, the mitogenomic lengths of species of Suillus were greater than those of other species of Boletales. We identified two main patterns of gene order arrangement in the members of the order Boletales. The Ka/Ks values of 15 protein-coding genes were Suillus was monophyletic. Phylogenetic results based on the internal transcribed spacer region and mitogenome were used to confirm the distribution of Suillus placidus in China. The results showed that the mitogenome was superior in distinguishing species compared with a single molecular fragment. This is the first study to investigate the mitogenome of Suillus, enriching the mitogenome information and providing basic data for the phylogeny, resource conservation, and genetic diversity of this genus.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is an important underlying cause of morbidity and mortality in patients with CTD. Serum Krebs von den Lungen-6 (KL-6) is an immune factor which has been related to the severity of ILD. This systematic review and meta-analysis aimed to evaluate the association between serum KL-6 and mortality of patients with CTD-ILD. Longitudinal studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Fifteen cohorts involving 1737 patients with CTD-ILD were included. During a mean follow-up of 35.3 months, 430 (24.8%) patients died. Compared to those with a lower KL-6 at admission, patients with a higher KL-6 were associated with a higher mortality risk during follow-up (risk ratio: 2.18, 95% confidence interval: 1.66 to 2.87, P < 0.001; I2 = 20%). Subgroup analysis showed a significant association in studies from Asian countries, but not in those from non-Asian countries; in studies with cutoff of KL-6 derived in receiver operating characteristic (ROC) curve analysis, but not in those derived from other methods; in studies with multivariate analysis, but not in those with univariate analysis (P for subgroup difference all < 0.05). The association was not significantly affected by different CTDs or methods for measuring serum KL-6. In conclusion, a high serum KL-6 may be a risk factor of increased mortality in patients with CTD-ILD.

Early mutation identification guides patients with colorectal cancer (CRC) toward targeted therapies. In the present study, 414 patients with CRC were enrolled, and amplicon-based targeted next-generation sequencing (NGS) was then performed to detect genomic alterations within the 73 cancer-related genes in the OncoAim panel. The overall mutation rate was 91.5 % (379/414). Gene mutations were detected in 38/73 genes tested. The most frequently mutated genes were TP53 (60.9 %), KRAS (46.6 %), APC (30.4 %), PIK3CA (15.9 %), FBXW7 (8.2 %), SMAD4 (6.8 %), BRAF (6.5 %), and NRAS (3.9 %). Compared with the wild type, TP53 mutations were associated with low microsatellite instability/microsatellite stability (MSI-L/MSS) (P = 0.007), tumor location (P = 0.043), and histological grade (P = 0.0009); KRAS mutations were associated with female gender (P = 0.026), distant metastasis (P = 0.023), TNM stage (P = 0.013), and histological grade (P = 0.004); APC mutations were associated with patients

Abstract A novel wideband high-selectivity substrate-integratedwaveguide (SIW) filtering antenna with controllable radiation nulls is proposed. This antenna is composed of a two-layered SIW resonator, two radiating slots on the top layer, and two coupling slots on the middle layer. A vertical SMA connector is located at the bottom and feeds two SIW cavities simultaneously. By adjusting the parameters of these slots, three radiation nulls will be achieved, and two radiation nulls can be easily controlled. For demonstration, one prototype of the filtering antenna is fabricated and measured. Measurement results show that the fractional bandwidth for |S11| < -10 dB is 8.9% (3.86-4.23 GHz), the gain is 6.08 dBi at center frequency 4.05 GHz, three radiation nulls are achieved at 3.7 GHz, 4.3 GHz, and 5.19 GHz, respectively. The out-of-band skirt selectivities of two sidebands are 150 and 332 dB/GHz, respectively.

Objective To investigate the correlations between multigene alterations and clinicopathological features in papillary thyroid carcinoma (PTC) samples. Methods In this retrospective study, 111 cytological specimens of thyroid nodules, including 74 PTC samples and 37 benign samples, were analyzed using a 22-gene mutation assay employing next-generation sequencing. Clinicopathological information was retrospectively collected and analyzed. Results Gene alterations were associated with a higher rate of lymph node metastasis (LNM) and thyroid capsular invasion, a lower rate of coexisting Hashimoto's thyroiditis, the classical PTC subtype, and younger age (

Late blight, caused by Phytophthora infestans, is one of the most serious diseases affecting potatoes (Solanum tuberosum L.). Long non-coding RNAs (lncRNAs) are transcripts with a length of more than 200 nucleotides that have no protein-coding potential. Few studies have been conducted on lncRNAs related to plant immune regulation in plants, and the molecular mechanisms involved in this regulation require further investigation. We identified and screened an lncRNA that specifically responds to P. infestans infection, namely, StlncRNA13558. P. infestans infection activates the abscisic acid (ABA) pathway, and ABA induces StlncRNA13558 to enhance potato resistance to P. infestans. StlncRNA13558 positively regulates the expression of its co-expressed PR-related gene StPRL. StPRL promotes the accumulation of reactive oxygen species and transmits a resistance response by affecting the salicylic acid hormone pathway, thereby enhancing potato resistance to P. infestans. In summary, we identified the potato late blight resistance lncRNA StlncRNA13558 and revealed its upstream and downstream regulatory relationship of StlncRNA13558. These results improve our understanding of plant-pathogen interactions’ immune mechanism and elucidate the response mechanism of lncRNA-target genes regulating potato resistance to P. infestans infection.

Abstract Smart nanoparticles, which can respond to biological cues or be guided by them, are emerging as a promising drug delivery platform for precise cancer treatment. The field of oncology, nanotechnology, and biomedicine has witnessed rapid progress, leading to innovative developments in smart nanoparticles for safer and more effective cancer therapy. In this review, we will highlight recent advancements in smart nanoparticles, including polymeric nanoparticles, dendrimers, micelles, liposomes, protein nanoparticles, cell membrane nanoparticles, mesoporous silica nanoparticles, gold nanoparticles, iron oxide nanoparticles, quantum dots, carbon nanotubes, black phosphorus, MOF nanoparticles, and others. We will focus on their classification, structures, synthesis, and intelligent features. These smart nanoparticles possess the ability to respond to various external and internal stimuli, such as enzymes, pH, temperature, optics, and magnetism, making them intelligent systems. Additionally, this review will explore the latest studies on tumor targeting by functionalizing the surfaces of smart nanoparticles with tumor-specific ligands like antibodies, peptides, transferrin, and folic acid. We will also summarize different types of drug delivery options, including small molecules, peptides, proteins, nucleic acids, and even living cells, for their potential use in cancer therapy. While the potential of smart nanoparticles is promising, we will also acknowledge the challenges and clinical prospects associated with their use. Finally, we will propose a blueprint that involves the use of artificial intelligence-powered nanoparticles in cancer treatment applications. By harnessing the potential of smart nanoparticles, this review aims to usher in a new era of precise and personalized cancer therapy, providing patients with individualized treatment options.

Thermal and electrical conductivity are essential when selecting materials for certain applications. We first present here an analysis of main influencing factors in electrical conductivity of as-cast Mg binary alloys, particularly the effect of the microsegregation of solutes during solidification. A theoretical model is then developed for electrical conductivity in binary Mg alloys, focusing on the effect of solute type and content, and applied to 8 Mg alloy systems with remarkable agreement. Electrical conductivity is then converted into thermal conductivity by Wiedemann–Franz's law, which is also applied to 8 Mg alloy systems, showing significant consistency. This finding provides an easy method for designing and evaluating the electrical/thermal conductivity for Mg alloys, or may be extended to other alloys.

Abstract Background In China, data on the prevalence and characteristics of comorbid stroke and traumatic brain injury (TBI) in real-world populations are still lacking but of paramount importance for the evidence-based prevention and control of the comorbidity of the two diseases. This study aimed to investigate the prevalence and characteristics of comorbid stroke and TBI in a real-world population. Methods In 2013, a nationally representative, door-to-door survey on stroke and TBI using a complex, multistage, probability sampling design was conducted among approximately 600,000 participants from 155 urban and rural areas in China (Ethic ID: KY2013-006-01). The weighted prevalence of comorbid stroke and TBI was estimated using individuals’ final weight. A Poisson regression analysis was used to compare the rate ratio of the comorbidity prevalence among different subgroups of the population, including age, sex, place of residence, and geographic location subgroups. For analyses of associations between the comorbidities and predictors of interest, all other variables were adjusted for in a multinomial logistic regression model. Results Among the 596,536 people, 219 patients with comorbid stroke and TBI were identified. The point prevalence of comorbid stroke and TBI weighted to the China 2010 census population was 29.30 (95% CI: 22.69–37.84) per 100,000 population in China. The adjusted prevalence of post-TBI stroke in patients with previous TBI was significantly higher than that of post-stroke TBI in patients with previous stroke (6021.3 vs. 811.1 per 100,000 people; rate ratio: 11.001; 95% CI: 8.069–14.998). Patients with nonconcussion had significantly higher rates of both pre-stroke TBI (odds ratio: 4.694; 95% CI: 3.296–6.687) and post-stroke TBI (odds ratio: 6.735; 95% CI: 3.719–12.194) than patients with concussion. Compared to patients with ischaemic stroke, patients with subarachnoid haemorrhage (odds ratio: 2.044; 95% CI: 1.097–3.809) and intracerebral haemorrhage (odds ratio: 1.903; 95% CI: 1.296–2.795) had significantly higher rates of post-TBI stroke. Conclusions The high prevalence of stroke among TBI patients is becoming a new public health issue. TBI patients, especially those with nonconcussion TBI, are more likely to develop comorbid stroke and TBI than stroke patients, especially ischaemic stroke patients.

Abstract Background Coronavirus disease 2019 (COVID-19) is a rapidly developing and sometimes lethal pulmonary disease. Accurately predicting COVID-19 mortality will facilitate optimal patient treatment and medical resource deployment, but the clinical practice still needs to address it. Both complete blood counts and cytokine levels were observed to be modified by COVID-19 infection. This study aimed to use inexpensive and easily accessible complete blood counts to build an accurate COVID-19 mortality prediction model. The cytokine fluctuations reflect the inflammatory storm induced by COVID-19, but their levels are not as commonly accessible as complete blood counts. Therefore, this study explored the possibility of predicting cytokine levels based on complete blood counts. Methods We used complete blood counts to predict cytokine levels. The predictive model includes an autoencoder, principal component analysis, and linear regression models. We used classifiers such as support vector machine and feature selection models such as adaptive boost to predict the mortality of COVID-19 patients. Results Complete blood counts and original cytokine levels reached the COVID-19 mortality classification area under the curve (AUC) values of 0.9678 and 0.9111, respectively, and the cytokine levels predicted by the feature set alone reached the classification AUC value of 0.9844. The predicted cytokine levels were more significantly associated with COVID-19 mortality than the original values. Conclusions Integrating the predicted cytokine levels and complete blood counts improved a COVID-19 mortality prediction model using complete blood counts only. Both the cytokine level prediction models and the COVID-19 mortality prediction models are publicly available at http://www.healthinformaticslab.org/supp/resources.php .

Mosquitoes are vectors of many important human diseases. The prolonged and widespread use of insecticides has led to the development of mosquito resistance to these insecticides. The gut microbiota is considered the master of host development and physiology; it influences mosquito biology, disease pathogen transmission, and resistance to insecticides. Understanding the role and mechanisms of mosquito gut microbiota in mosquito insecticide resistance is useful for developing new strategies for tackling mosquito insecticide resistance. We searched online databases, including PubMed, MEDLINE, SciELO, Web of Science, and the Chinese Science Citation Database. We searched all terms, including microbiota and mosquitoes, or any specific genera or species of mosquitoes. We reviewed the relationships between microbiota and mosquito growth, development, survival, reproduction, and disease pathogen transmission, as well as the interactions between microbiota and mosquito insecticide resistance. Overall, 429 studies were included in this review after filtering 8139 search results. Mosquito gut microbiota show a complex community structure with rich species diversity, dynamic changes in the species composition over time (season) and across space (environmental setting), and variation among mosquito species and mosquito developmental stages (larval vs. adult). The community composition of the microbiota plays profound roles in mosquito development, survival, and reproduction. There was a reciprocal interaction between the mosquito midgut microbiota and virus infection in mosquitoes. Wolbachia, Asaia, and Serratia are the three most studied bacteria that influence disease pathogen transmission. The insecticide resistance or exposure led to the enrichment or reduction in certain microorganisms in the resistant mosquitoes while enhancing the abundance of other microorganisms in insect-susceptible mosquitoes, and they involved many different species/genera/families of microorganisms. Conversely, microbiota can promote insecticide resistance in their hosts by isolating and degrading insecticidal compounds or altering the expression of host genes and metabolic detoxification enzymes. Currently, knowledge is scarce about the community structure of mosquito gut microbiota and its functionality in relation to mosquito pathogen transmission and insecticide resistance. The new multi-omics techniques should be adopted to find the links among environment, mosquito, and host and bring mosquito microbiota studies to the next level.

Sooty mould (SM) disease affects the growth, development and metabolism of plants and reduces the commodity and economic value of crops. SM disease is one of the important leaf diseases in tea plants. Nonetheless, studies on the effect of SM disease in tea plants are rare. Herein, we found that SM disease disrupted the cell morphology and structure and reduced the contents of caffeine, theanine, and catechins in the mature leaves of tea plants. Transcriptome analysis revealed that SM disease inhibited the biosynthesis of lignin, chlorophyll, catechin, caffeine, and theanine and affected the plant-pathogen interactions in the mature leaves of tea plants by downregulating gene expression. In addition, two fungal isolates, MTzyqA and MTzyqB, were obtained from the mature leaves of diseased tea plants. These strains were identified as Cladosporium pseudocladosporioides by mulitgene phylogenetic analysis, and they grew epiphytically on the leaves of tea plants. The biocontrol bacteria JT68, ZGT5, and BX1 had obvious inhibitory effect on MTzyqA and MTzyqB. These results provide a basis for understanding the effect of SM disease in tea plants.

To obtain high-quality bovine oocytes, the effects of vitamin C (VC) on the IVM of bovine oocytes and early embryo development were investigated. The results showed the following. (1) The IVM medium containing 50 µg/mL VC improved the oocyte maturation rate but did not affect the parthenogenetic embryo development. (2) The IVC medium containing 20 µg/mL VC improved the cleavage rate of the IVF embryos and enhanced the mRNA transcriptions of pluripotency gene Oct4, Sox2, Cdx2, and Nanog in the blastocysts but had no effects on the blastocyst rate. (3) Combining supplementation of 50 µg/mL VC in IVM medium + 20 µg/mL VC in IVC medium (named as VC 50/20, similar hereinafter) elevated the cleavage rate of IVF embryos and enhanced the mRNA expressions of Oct4, Sox2, Cdx2, and Nanog in the blastocysts. (4) Combination of VC 0/20 and VC 50/20 enhanced the transcription of anti-apoptotic gene Bcl-2 and VC 50/0 weakened the transcription of pro-apoptotic gene Bax, while VC 0/40 and VC 0/60 increased Bax expression and diminished the Bcl-2/Bax ratio in blastocysts. Together, employing 50 µg/mL VC improves the IVM of bovine oocytes and combination of VC 50/20 potentially changes bovine embryo quality by enhancing the expressions of the pluripotency genes and regulating the expressions of apoptosis-related genes.

The expansion of the construction land scale has been vital in supporting rapid economic development and meeting social needs. However, the spatial heterogeneity in the effect of construction land scale on carbon emission intensity at the county level remains underexplored. Therefore, comprehensively investigating the relation between the construction land transfer scale and carbon emission intensity holds substantial research value. Using panel data from 2007 to 2021, this study analyzes the spatiotemporal differentiation characteristics of carbon emission intensity and the effect of construction land scale on carbon emission intensity at the county level in Jiangsu Province, China. The findings reveal that carbon emission intensity at the county level in Jiangsu Province generally exhibits a continuous downward trend over time and a spatial distribution characterized by a gradual decrease from the southern counties to the central and northern counties. Moreover, there is a significant positive relation between the construction land transfer scale and carbon emission intensity, a conclusion supported by robustness tests. Furthermore, mediating analysis indicates that reduction of the construction land transfer scale exhibits a significant promoting effect on green technology innovation and industrial structure upgrading, which, in turn, has a significant inhibitory effect on carbon emission intensity. The impact of the construction land transfer scale from different sources, supply methods, types, and of county economic strength on carbon emission intensity has significant heterogeneity.

Hypergolic ignition of H2O2 and MEA-NaBH4 by off-center collision of their droplets was experimentally studied, focusing on the characteristics and mechanism of droplet mixing, droplet heating and evaporation, and gas-phase ignition. The whole collision ignition process was divided into five stages, which were compared, respectively, with that of head-on collision. Under the condition of a slightly off-center collision (for cases where B < 0.35), H2O2 droplets penetrate MEA-NaBH4 droplets after the collision and coalesce with it, but the internal H2O2 drop inside the MEA-NaBH4 droplet does not form a stable sphere. Instead, it rotates and expands inside the mixed droplet. With B increasing to 0.59, the droplets no longer coalesce after collision but separate away, forming satellite droplets. In such cases, multi-ignition mode is observed. When B increases to a certain extent, specifically, 0.85, a grazing collision is observed such that no mass transfer exists during the interaction of droplets, which leads to ignition failure. A theoretical model quantifying droplet swelling rate was established to calculate the volume change of the droplet. It was found that the swelling can be attributed to the flash boiling of superheated internal H2O2 fluid. Meanwhile, the ignition delay time was found to linearly decrease with B at various Wes until the extent where the chemical reaction takes over control, leading to an almost constant time delay defined as RDT. Additionally, the regime of ignition modes corresponding to different droplet mixing features is summarized in the We-B parametric space.

With the advancement of artificial intelligence and deep neural networks, the ease of image generation and editing has increased significantly.Consequently, the occurrence of malicious tampering and forgery using image generation tools is on the rise, posing a significant threat to multimedia security and social stability.Therefore, it is crucial to research detection methods for forged faces.Face tampering and forgery can occur through various means and tools, leaving different levels of forgery traces during the tampering process.These traces can be partly reflected in the image noise.From the perspective of image noise, the noise components reflecting tampering traces of forged faces were extracted through a noise removal module.Furthermore, noise attention was generated to guide the backbone network in the detection of forged faces.The training of the noise removal module was supervised using SRM filters.In order to strengthen the guidance of the noise removal module, the noise obtained by the noise removal module was added back to the real face image, forming a pair of supervised training samples in a self-supervised manner.The experimental results illustrate that the noise features obtained by the noise removal module have a good degree of discrimination.Experiments were also conducted on several public datasets, and the proposed method achieves an accuracy of 98.32% on the Celeb-DF dataset, 92.61% on the DFDC dataset, and more than 94% on the FaceForensics++ dataset, thus proving the effectiveness of the proposed method.

Abstract Background The emergence of COVID-19 and the implementation of preventive measures and behavioral changes have led to a significant decrease in the prevalence of other respiratory viruses. However, the manner in which seasonal viruses will reemerge in the absence of COVID-19-related restrictions remains unknown. Methods Patients presenting with influenza-like illness in two hospitals in Beijing were subjected to testing for COVID-19, influenza A, and influenza B to determine the causative agent for viral infections. The prevalence of influenza B across China was confirmed using data from the Centers for Disease Control, China (China CDC). Clinical characteristics, laboratory findings, imaging results, and mortality data were collected for a cohort of 70 hospitalized patients with confirmed influenza B from 9 hospitals across China. Results Starting from October 2021, a substantial increase in the number of patients visiting the designated fever clinics in Beijing was observed, with this trend continuing until January 2022. COVID-19 tests conducted on these patients yielded negative results, while the positivity rate for influenza rose from approximately 8% in October 2021 to over 40% by late January 2022. The cases started to decline after this peak. Data from China CDC confirmed that influenza B is a major pathogen during the season. Sequencing of the viral strain revealed the presence of the Victoria-like lineage of the influenza B strain, with minor variations from the Florida/39/2018 strain. Analysis of the hospitalized patients' characteristics indicated that severe cases were relatively more prevalent among younger individuals, with an average age of 40.9 ± 24.1 years. Among the seven patients who succumbed to influenza, the average age was 30 ± 30.1 years. These patients exhibited secondary infections involving either bacterial or fungal pathogens and displayed elevated levels of cell death markers (such as LDH) and coagulation pathway markers (D-dimer). Conclusion Influenza B represents a significant infection threat and can lead to substantial morbidity and mortality, particularly among young patients. To mitigate morbidity and mortality rates, it is imperative to implement appropriate vaccination and other preventive strategies.

Abstract Background Maintaining homeostasis of Ca2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca2+ signaling and key cellular functions. Although Ca2+ depletion has been known to cause ER stress which in turn activates the unfolded protein response (UPR), how UPR sensors/transducers respond to excess Ca2+ when ER stores are overloaded remain largely unclear. Results Here, we report for the first time that overloading of ER Ca2+ can directly sensitize the IRE1α-XBP1 axis. The overloaded ER Ca2+ in TMCO1-deficient cells can cause BiP dissociation from IRE1α, promote the dimerization and stability of the IRE1α protein, and boost IRE1α activation. Intriguingly, attenuation of the over-activated IRE1α-XBP1s signaling by a IRE1α inhibitor can cause a significant cell death in TMCO1-deficient cells. Conclusions Our data establish a causal link between excess Ca2+ in ER stores and the selective activation of IRE1α-XBP1 axis, underscoring an unexpected role of overload of ER Ca2+ in IRE1α activation and in preventing cell death.

Abstract Background The appropriate administration regimen of polymyxin B is yet controversial. The present study aimed to explore the optimal dose of polymyxin B under therapeutic drug monitoring (TDM) guidance. Methods In China’s Henan province, 26 hospitals participated in a randomized controlled trial. We included patients with sepsis caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) susceptible to polymyxin B. The patients were randomly divided into a high-dose (HD) group or a low-dose (LD) group and received 150 mg loading dose, 75 mg every 12 h and 100 mg loading dose, 50 mg every 12 h, respectively. TDM was employed to determine if the dose of polymyxin B needs adjustment based on the area under the concentration–time curve across 24 h at a steady state (ssAUC0–24) of 50–100 mg h/L. The primary outcome was the 14-day clinical response, and the secondary outcomes included 28- and 14-day mortality. Results This trial included 311 patients, with 152 assigned to the HD group and 159 assigned to the LD group. Intention-to-treat analysis showed that the 14-day clinical response was non-significant (p = 0.527): 95/152 (62.5%) in the HD group and 95/159 (59.7%) in the LD group. Kaplan–Meier’s 180-day survival curve showed survival advantage in the HD group than in the LD group (p = 0.037). More patients achieved the target ssAUC0–24 in the HD than in the LD group (63.8% vs. 38.9%; p = 0.005) and in the septic shock subgroup compared to all subjects (HD group: 71.4% vs. 63.8%, p = 0.037; LD group: 58.3% vs. 38.9%, p = 0.0005). Also, the target AUC compliance was not correlated with clinical outcomes but with acute kidney injury (AKI) (p = 0.019). Adverse events did not differ between the HD and LD groups. Conclusion A fixed polymyxin B loading dose of 150 mg and a maintenance dose of 75 mg every 12 h was safe for patients with sepsis caused by CR-GNB and improves long-term survival. The increased AUC was associated with increased incidence of AKI, and TDM results were valued to prevent AKI. Trial registration Trial registration ClinicalTrials.gov: ChiCTR2100043208, Registration date: January 26, 2021.

Abstract Background We have previously demonstrated that ginsenoside compound K can attenuate the formation of atherosclerotic lesions. Therefore, ginsenoside compound K has potential for atherosclerosis therapy. How to improve the druggability and enhance the antiatherosclerotic activity of ginsenoside compound K are the core problems in the prevention and treatment of atherosclerosis. CKN is a ginsenoside compound K derivative that was previously reported to have excellent antiatherosclerotic activity in vitro, and we have applied for international patents for it. Methods Male C57BL/6 ApoE−/− mice were fed a high-fat and high-choline diet to induce atherosclerosis and were subjected to in vivo studies. In vitro, the CCK-8 method was applied to evaluate cytotoxicity in macrophages. Foam cells were utilized, and cellular lipid determination was performed for in vitro studies. The area of atherosclerotic plaque and fatty infiltration of the liver were measured by image analysis. Serum lipid and liver function were determined by a seralyzer. Immunofluorescence and western blot analysis were conducted to explore the alterations in the expression levels of lipid efflux-related proteins. Molecular docking, reporter gene experiments and cellular thermal shift assays were used to verify the interaction between CKN and LXRα. Results After confirming the therapeutic effects of CKN, molecular docking, reporter gene experiments and cellular thermal shift assays were used to predict and investigate the antiatherosclerotic mechanisms of CKN. CKN exhibited the greatest potency, with a 60.9% and 48.1% reduction in en face atherosclerotic lesions on the thoracic aorta and brachiocephalic trunk, reduced plasma lipid levels and decreased foam cell levels in the vascular plaque content in HHD-fed ApoE−/− mice. Moreover, CKN in the present study may exert its antiatherosclerotic effects through activated ABCA1 by promoting LXRα nuclear translocation and reducing the adverse effects of LXRα activation. Conclusions Our results revealed that CKN prevented the formation of atherosclerosis in ApoE−/− mice by activating the LXRα pathway.

Abstract Aim To translate and test the psychometric properties of a Chinese version scale to measure the Fear of Activity in patients with Coronary Artery Disease. Design A cross‐sectional design. Methods The translation of the scale to measure Fear of Activity in Patients with Coronary Artery Disease included three steps, forward‐back translation, expert discussion and pilot survey. The internal consistency and test–retest reliability were used to assess the reliability of the Chinese version scale of the Fear of Activity. Content, construct, criterion, and known‐group validity of the scale were also evaluated. Data Sources A total of 275 patients with Coronary Artery Disease were recruited from a university‐affiliated hospital in Guangzhou, southern China. Results The overall content validity index of the Chinese version scale of the Fear of Activity in Patients with Coronary Artery Disease was 0.90. Principal component analyses extracted four factors with a cumulative variance contribution of 57.5%. There is a strong correlation (r = 0.83) between this scale and Tampa Scale for Kinesiophobia Heart. The total scores of the Chinese version scale of the Fear of Activity in female patients were higher than those in male patients with Coronary Artery Disease, indicating that the scale was able to distinguish the differences between low and high score groups. The Internal consistency and test–retest reliability coefficients of the scale were 0.74 and 0.82, respectively. Conclusion The Chinese version scale of the Fear of Activity in Patients with Coronary Artery Disease, which consists of 21 items with four dimensions, is a reliable and valid instrument to evaluate the fear of activity in patients with Coronary Artery Disease. Implications for the Profession and/or Patient Care The Chinese version scale of the Fear of Activity in Patients with Coronary Artery Disease can be used to assess the levels of fear of activity in patients with Coronary Artery Disease and explores the factors that influence fear of activity in the population. Impact This study translates and confirms the psychometric properties of the Chinese version scale of the Fear of Activity in Patients with Coronary Artery Disease in China. It is useful in both research and clinical fields to explore the fear of activity and its associated factors in patients with Coronary Artery Disease. Reporting Method The study design followed the guideline of Strengthening the Reporting of Observational Studies in Epidemiology statement. Patient or Public Contribution Patients in a university‐affiliated hospital participated in this study and contributed to data collection.

Background: Cancer is a significant global health problem that continues to cause a high number of deaths worldwide. Traditional cancer treatments often come with risks that can compromise the functionality of vital organs. As a potential alternative to these conventional therapies, Anticancer peptides (ACPs) have garnered attention for their small size, high specificity, and reduced toxicity, making them as a promising option for cancer treatments.Methods: However, the process of identifying effective ACPs through wet-lab screening experiments is time-consuming and requires a lot of labor. To overcome this challenge, a deep ensemble learning method is constructed to predict anticancer peptides (ACPs) in this study. To evaluate the reliability of the framework, four different datasets are used in this study for training and testing. During the training process of the model, integration of feature selection methods, feature dimensionality reduction measures, and optimization of the deep ensemble model are carried out. Finally, we explored the interpretability of features that affected the final prediction results and built a web server platform to facilitate anticancer peptides prediction, which can be used by all researchers for further studies. This web server can be accessed at http://lmylab.online:5001/.Results: The result of this study achieves an accuracy rate of 98.53% and an AUC (Area under Curve) value of 0.9972 on the ACPfel dataset, it has improvements on other datasets as well.

A coal model containing gangue was established by discrete elements to study the forces occurring when a shearer cuts coal, and a rigid-flexible coupled shearer section model was established in RecurDyn; the drum cutting process was simulated through bidirectional coupling. The dynamic distribution of the force chain was obtained when cutter teeth cut the coal rock. During the cutting process, the coal rock failure is caused by normal and tangential forces, with the latter having a major role. The ratio of the average tangential force to normal force was 1.34~1.79. When the rock is in the middle of the coal seam, the force (including normal and tangential forces) on the rock is the highest. Moreover, the force on the rock-coal interface is greater than that on the coal-rock interface. The results show that the force on the coal decreases with the increases in rotation speed. In contrast, the number of broken bonds increases. Further, the number of broken bonds and the force of coal increased nonlinearly with traction speed. Finally, the increase of tooth mounting angle decreased the force on the coal rock and the number of broken bonds, followed by an increase. As such, this study provides a reference for further theoretical research on forces in coal cutting.

Background Pharmacogenomics (PGx) is a promising tool to realise tailored drug therapy for depression.Aims To investigate the treatment efficacy of PGx for treatment-resistant depression (TRD) compared with treatment as usual.Methods A systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science and PsycINFO to identify relevant studies published from inception to 15 April 2023. Two-arm randomised controlled trials (RCTs) exploring the efficacy of PGx-guided versus unguided treatment for TRD were included. The risk of bias in the included studies was evaluated using the Cochrane risk of bias assessment tool. The overall quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.Results Seven RCTs (n=3003) comparing PGx-guided (n=1492) and unguided (n=1511) groups were identified and analysed. PGx-guided treatment was superior to treatment as usual in response (relative risk (RR)=1.31; 95% confidence interval (95% CI): 1.15 to 1.49; p

Morphological characters currently used to differentiate Caragana opulens as a species have been found to be insufficient and inconsistent. Through extensive research and comparisons of specimens, it has been revealed that C. opulens and its synonyms have overlapping geographical distributions, and that typification is necessary for C. opulens. Therefore, a lectotype is designated for the name C. opulens, with comments on its typification. Additionally, the current typification status is discussed for all its synonyms, accompanied by substantive notes.

Transetherifications between ethers and alcohols are fundamental organic reactions that are frequently used for the preparations of unsymmetrical ethers. In this article, the authors challenge the fundamental tenets of the traditional transetherification mechanism via systematic experimental and computational investigations of a Re2O7-mediated annulation.

Abstract Background Mosquitoes are important vectors for a range of diseases, contributing to high rates of morbidity and mortality in the human population. Culex pipiens pallens is dominant species of Culex mosquito in northern China and a major vector for both West Nile virus and Bancroftian filariasis. Insecticide application were largely applied to control the mosquito-mediated spread of these diseases, contributing to increasing rates of resistance in the mosquito population. The voltage-gated sodium channel (Vgsc) gene is the target site of pyrethroids, and mutations in this gene cause knockdown resistance (kdr). While these kdr mutations are known to be critical to pyrethroid resistance, their evolutionary origins remain poorly understood. Clarifying the origins of these mutations is potential to guide further vector control and disease prevention efforts. Accordingly, the present study was designed to study the evolutionary genetics of kdr mutations and their association with the population structure of Cx. p. pallens in Shandong province, China. Methods Adult Culex females were collected from Shandong province and subjected to morphological identification under a dissection microscope. Genomic DNA were extracted from the collected mosquitoes, the Vgsc gene were amplified via PCR and sequenced to assess kdr allele frequencies, intron polymorphisms, and kdr codon evolution. In addition, population genetic diversity and related population characteristics were assessed by amplifying and sequencing the mitochondrial cytochrome C oxidase I (COI) gene. Results Totally, 263 Cx. p. pallens specimens were used for DNA barcoding and sequencing analyses to assess kdr allele frequencies in nine Culex populations. The kdr codon L1014 in the Vgsc gene identified two non-synonymous mutations (L1014F and L1014S) in the analyzed population. These mutations were present in the eastern hilly area and west plain region of Shandong Province. However, only L1014F mutation was detected in the southern mountainous area and Dongying city of Shandong Province, where the mutation frequency was low. Compared to other cities, population in Qingdao revealed significant genetic differentiation. Spatial kdr mutation patterns are likely attributable to some combination of prolonged insecticide-mediated selection coupled with the genetic isolation of these mosquito populations. Conclusions These data suggest that multiple kdr alleles associated with insecticide resistance are present within the Cx. p. pallens populations of Shandong Province, China. The geographical distributions of kdr mutations in this province are likely that the result of prolonged and extensive insecticide application in agricultural contexts together with frequent mosquito population migrations. In contrast, the low-frequency kdr mutation detected in central Shandong Province populations may originate from the limited selection pressure in this area and the relative genetic isolation. Overall, the study compares the genetic patterns revealed by a functional gene with a neutral marker and demonstrates the combined impact of demographic and selection factors on population structure.

Abstract Background Future distribution of dengue risk is usually predicted based on predicted climate changes using general circulation models (GCMs). However, it is difficult to validate the GCM results and assess the uncertainty of the predictions. The observed changes in climate may be very different from the GCM results. We aim to utilize trends in observed climate dynamics to predict future risks of Aedes albopictus in China. Methods We collected Ae. albopictus surveillance data and observed climate records from 80 meteorological stations from 1970 to 2021. We analyzed the trends in climate change in China and made predictions on future climate for the years 2050 and 2080 based on trend analyses. We analyzed the relationship between climatic variables and the prevalence of Ae. albopictus in different months/seasons. We built a classification tree model (based on the average of 999 runs of classification and regression tree analyses) to predict the monthly/seasonal Ae. albopictus distribution based on the average climate from 1970 to 2000 and assessed the contributions of different climatic variables to the Ae. albopictus distribution. Using these models, we projected the future distributions of Ae. albopictus for 2050 and 2080. Results The study included Ae. albopictus surveillance from 259 sites in China found that winter to early spring (November–February) temperatures were strongly correlated with Ae. albopictus prevalence (prediction accuracy ranges 93.0–98.8%)—the higher the temperature the higher the prevalence, while precipitation in summer (June–September) was important predictor for Ae. albopictus prevalence. The machine learning tree models predicted the current prevalence of Ae. albopictus with high levels of agreement (accuracy > 90% and Kappa agreement > 80% for all 12 months). Overall, winter temperature contributed the most to Ae. albopictus distribution, followed by summer precipitation. An increase in temperature was observed from 1970 to 2021 in most places in China, and annual change rates varied substantially from -0.22 ºC/year to 0.58 ºC/year among sites, with the largest increase in temperature occurring from February to April (an annual increase of 1.4–4.7 ºC in monthly mean, 0.6–4.0 ºC in monthly minimum, and 1.3–4.3 ºC in monthly maximum temperature) and the smallest in November and December. Temperature increases were lower in the tropics/subtropics (1.5–2.3 ºC from February–April) compared to the high-latitude areas (2.6–4.6 ºC from February–April). The projected temperatures in 2050 and 2080 by this study were approximately 1–1.5 °C higher than those projected by GCMs. The estimated current Ae. albopictus risk distribution had a northern boundary of north-central China and the southern edge of northeastern China, with a risk period of June–September. The projected future Ae. albopictus risks in 2050 and 2080 cover nearly all of China, with an expanded risk period of April–October. The current at-risk population was estimated to be 960 million and the future at-risk population was projected to be 1.2 billion. Conclusions The magnitude of climate change in China is likely to surpass GCM predictions. Future dengue risks will expand to cover nearly all of China if current climate trends continue.

Key points A significant linear correlation exists between resting LA strain and exercise capacity in CHF patients receiving beta-blocker therapy. LA reservoir strain is the strongest independent predictor of decreased exercise capacity among all LA strain parameters. LA booster strain is also an independent predictor of decreased exercise capacity.