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Abstract Evidence shows that inflammatory responses play an essential role in the development of brain metastases (BM). The goal of this meta-analysis was to critically evaluate the literature regarding the use of the neutrophil to lymphocyte ratio (NLR) to predict the prognosis of patients with BM to help clinicians institute early interventions and improve outcomes. We conducted systematic review and meta-analysis, utilizing data from prominent databases, including PubMed, Cochrane Library and China National Knowledge Infrastructure databases. Our inclusion criteria encompassed studies investigating the studies that assessed the association between NLR and overall survival (OS). We included 11 articles, with 2629 eligible patients, to evaluate the association between NLR and OS. High NLR was significantly associated with shorter OS, with a pooled hazard ratio (HR) of 1.82 (95% CI 1.57–2.11). Subgroup analysis revealed that this association was consistent across different regions, with HRs of 2.03 (95% CI 1.67–2.46) in Asian populations and 1.58 (95% CI 1.35–1.84) in non-Asian populations. Additionally, in a subgroup analysis based on NLR cut-off values, patients with NLR ≥ 3 had an HR of 1.69 (95% CI 1.46–1.96), while those with NLR

Abstract Cryo-electron microscopy (cryo-EM) technique is widely used for protein structure determination. Current automatic cryo-EM protein complex modeling methods mostly rely on prior chain separation. However, chain separation without sequence guidance often suffers from errors caused by cross-chain interaction or noise densities, which would accumulate and mislead the subsequent steps. Here, we present EModelX, a fully automated cryo-EM protein complex structure modeling method, which achieves sequence-guiding modeling through cross-modal alignments between cryo-EM maps and protein sequences. EModelX first employs multi-task deep learning to predict Cα atoms, backbone atoms, and amino acid types from cryo-EM maps, which is subsequently used to sample Cα traces with amino acid profiles. The profiles are then aligned with protein sequences to obtain initial structural models, which yielded an average RMSD of 1.17 Å in our test set, approaching atomic-level precision in recovering PDB-deposited structures. After filling unmodeled gaps through sequence-guiding Cα threading, the final models achieved an average TM-score of 0.808, outperforming the state-of-the-art method. The further combination with AlphaFold can improve the average TM-score to 0.911. Analyzes conducted by comparing some EModelX-built models and PDB structures highlight its potential to improve PDB structures. EModelX is accessible at https://bio-web1.nscc-gz.cn/app/EModelX .

Abstract Introduction Sepsis is a life-threatening condition that poses a globally high mortality rate. Identifying risk factors is crucial. Insulin resistance and the TYG index, associated with metabolic disorders, may play a role. This study explores their correlation with mortality in non-diabetic septic patients. Methods This retrospective cohort study used data from the MIMIC-IV (version 2.1) database, which includes over 50,000 ICU admissions from 2008 to 2019 at Beth Israel Deaconess Medical Center in Boston. We included adult patients with sepsis who were admitted to the intensive care unit in the study. The primary outcome was to evaluate the ability of TYG to predict death at 28-day of hospital admission in patients with sepsis. Results The study included 2213 patients with sepsis, among whom 549 (24.8%) died within 28 days of hospital admission. We observed a non-linear association between TYG and the risk of mortality. Compared to the reference group (lower TYG subgroup), the 28-day mortality increased in the higher TYG subgroup, with a fully adjusted hazard ratio of 2.68 (95% CI: 2.14 to 3.36). The area under the curve (AUC) for TYG was 67.7%, higher than for triglycerides alone (AUC = 64.1%), blood glucose (AUC = 62.4%), and GCS (AUC = 63.6%), and comparable to SOFA (AUC = 69.3%). The final subgroup analysis showed no significant interaction between TYG and each subgroup except for the COPD subgroup (interaction P-values: 0.076–0.548). Conclusion In our study, TYG can be used as an independent predictor for all-cause mortality due to sepsis within 28 days of hospitalization.

Abstract Heat shuttling phenomenon is characterized by the presence of a non-zero heat flow between two bodies without net thermal bias on average. It was initially predicted in the context of nonlinear heat conduction within atomic lattices coupled to two time-oscillating thermostats. Recent theoretical works revealed an analog of this effect for heat exchanges mediated by thermal photons between two solids having a temperature dependent emissivity. In this paper, we present the experimental proof of this effect using systems made with composite materials based on phase change materials. By periodically modulating the temperature of one of two solids we report that the system akin to heat pumping with a controllable heat flow direction. Additionally, we demonstrate the effectiveness of a simultaneous modulation of two temperatures to control both the strength and direction of heat shuttling by exploiting the phase delay between these temperatures. These results show that this effect is promising for an active thermal management of solid-state technology, to cool down solids, to insulate them from their background or to amplify heat exchanges.

Abstract The aim of the study was to analyze the change trend of serum ALP over time and identify factors influencing its levels in peritoneal dialysis patients. Then to investigate the impact of serum ALP changes on calcium and phosphorus metabolism in single peritoneal dialysis center utilizing repeated measurement data. A retrospective cohort study was conducted with a total follow-up duration of 30 months. Serum ALP and other biomarkers, including calcium (Ca), phosphorus (P), 25(OH)D, intact parathyroid hormone (iPTH), albumin(ALB), and hemoglobin(Hb) were measured every 3 months. The generalized estimation equation (GEE) was utilized to analyze the change trend of serum ALP over time, and to assess whether there were differences in changes over time between different genders and different primary disease groups. Additionally, factors influencing serum ALP levels were analyzed, and the impact of serum ALP changes on calcium and phosphorus metabolism was also explored. A total of 34 patients were included in the study. Serum ALP and other indicators were measured repeatedly, with a maximum of 8 times and a minimum of 4 times. The median of serum ALP values at all measurement times for all selected patients was 89 U/L. The GEE analysis revealed that serum ALP gradually increased with time, and patients in diabetes group increased faster than those in non-diabetes group. A positive correlation was observed between serum ALP and dialysis duration, also between serum ALP and hemoglobin. However, variations in serum ALP did not significantly affect serum corrected calcium, phosphorus, or iPTH concentrations. The serum ALP levels of peritoneal dialysis patients increase gradually over time, and the concentrations are influenced by dialysis duration. The changes in serum ALP values do not have a significant impact on serum calcium, phosphorus, and iPTH levels.

Titanium (Ti) alloys have been widely applied clinically due to their good biocompatibility, corrosion resistance and mechanical stability. However, how to improve the weak osteointegration caused by their intrinsic bio-inertness has been a long-standing puzzle. Osteogenic-related cells, endothelial cells (ECs) and macrophages are the main cells involved in osteointegration. In recent years, surface topography based on Ti alloys, which mimics the topographical cues of the extracellular matrix (ECM), has been confirmed to precisely regulate these cells' fate to improve osteointegration. More importantly, while serving as a physicomechanical stimuli, topographic surface modification is considered more biosafe and stable than biochemical cues. Nevertheless, how different topographic modifications affect cell behavior and the specific mechanisms involved remain elusive. In this review, we highlight the regulation of surface topography based on Ti alloys on the behaviors of bone repair-related cells, such as osteogenic-related cells, ECs and macrophages, and summarize the activated intracellular mechanotransduction pathways, which aims to provide basis and support for further research on osteointegration of Ti alloys.

IntroductionScoliosis is a pathological spine structure deformation, predominantly classified as “idiopathic” due to its unknown etiology. However, it has been suggested that scoliosis may be linked to polygenic backgrounds. It is crucial to identify potential Adolescent Idiopathic Scoliosis (AIS)-related genetic backgrounds before scoliosis onset.MethodsThe present study was designed to intelligently parse, decompose and predict AIS-related variants in ClinVar database. Possible AIS-related variant records downloaded from ClinVar were parsed for various labels, decomposed for Dinucleotide Compositional Representation (DCR) and other traits, screened for high-risk genes with statistical analysis, and then learned intelligently with deep learning to predict high-risk AIS genotypes.ResultsResults demonstrated that the present framework is composed of all technical sections of data parsing, scoliosis genotyping, genome encoding, machine learning (ML)/deep learning (DL) and scoliosis genotype predicting. 58,000 scoliosis-related records were automatically parsed and statistically analyzed for high-risk genes and genotypes, such as FBN1, LAMA2 and SPG11. All variant genes were decomposed for DCR and other traits. Unsupervised ML indicated marked inter-group separation and intra-group clustering of the DCR of FBN1, LAMA2 or SPG11 for the five types of variants (Pathogenic, Pathogeniclikely, Benign, Benignlikely and Uncertain). A FBN1 DCR-based Convolutional Neural Network (CNN) was trained for Pathogenic and Benign/ Benignlikely variants performed accurately on validation data and predicted 179 high-risk scoliosis variants. The trained predictor was interpretable for the similar distribution of variant types and variant locations within 2D structure units in the predicted 3D structure of FBN1.DiscussionIn summary, scoliosis risk is predictable by deep learning based on genomic decomposed features of DCR. DCR-based classifier has predicted more scoliosis risk FBN1 variants in ClinVar database. DCR-based models would be promising for genotype-to-phenotype prediction for more disease types.

BackgroundThe differentiation of hematopoietic cells is significantly affected by cell metabolic activity. However, despite increasing interest in this field, there has been no comprehensive investigation of the metabolic functions of human hematopoietic cells during specific phases of differentiation. Thus, this study was conducted to develop a method for comparing hematopoietic cell lineage differentiation based on the metabolic functions of the cell. The metabolic activity of human umbilical cord-derived hematopoietic cells was examined during various phases of differentiation, specifically, hematopoietic stem cells (HSCs), hematopoietic progenitor cells, and differentiated blood cells. This approach was used to develop comprehensive metabolic maps corresponding to the different stages.ResultsHSCs were found to have robust fatty acid (FA) synthesis, FA oxidation, pentose phosphate pathway (PPP) activity, and glucose uptake, shown by their significantly higher expression of ACAC, CPT1A, G6PD, and GLUT1 as compared to differentiated pluripotent progenitor cells, common myeloid progenitors, megakaryocyte erythroid progenitors, lympho-myeloid primed progenitors, and granulocyte-macrophage progenitor cell populations. In monocytic differentiation, higher levels of ACAC, ASS1, ATP5A, CPT1A, G6PD, GLUT1, IDH2, PRDX2, and HK1 protein expression were evident in classical and intermediate monocytes relative to non-classical monocytes, consistent with high anabolic and catabolic levels. Compared with myelocytes and mature cells, the meta-myelocyte and pro-myelocyte populations of granulocytes show significantly elevated levels of ACAC, ASS1, ATP5A, CPT1A, G6PD, IDH2, PRDX2, and HK. In contrast to naïve and regulatory B cells, pro-B cells had higher levels of oxidative phosphorylation, while regulatory B cells showed greater PPP activity, glucose uptake, and tricarboxylic acid cycle activity. The analyses of T cells also indicated significantly higher ACAC, ASS1, ATP5A, CPT1A, G6PD, GLUT1, IDH2, PRDX2, and HK1 expression levels in CD4+ populations compared with CD8+ populations.ConclusionsThe results provide comprehensive analytical methods and reference values for future systematic studies into the metabolic functions of various cord blood-derived hematopoietic cell populations in different pathological or physiological conditions. These findings could also contribute to research on the connection between cellular metabolism and cancer or aging.

In recent years, overwhelming evidence has emphasized the crucial role of inflammation in the pathogenesis of PD. However, the exact mechanisms by which inflammation damages dopaminergic neurons in PD are still unclear. Therefore, we generated a MPTP-induced PD mouse model and performed spatial transcriptomic sequencing to provide more insight into the process of PD development at specific brain regions. Our results indicate that the pathological changes of PD are mainly manifested in the midbrain, especially in the substantia nigra region, with significant reductions in oligodendrocytes and Agt-labeled astrocytes and an increase in Gfap-labeled astrocytes. Macrophages displayed an increasing trend in the PD environment, indicating a pattern of immune modulation induced by PD. Moreover, pathway analysis revealed significant impairments in ion migration ability, abnormal Ca2+ channels, cAMP signaling, and synaptic damage in PD. Significant downregulation of Mt1 and Mt2 and upregulation of Atp1b2, Gpi1, and Cox6a1 in PD further underscored the occurrence of intense inflammation and immune alterations. On the basis of these findings, we have validated the significant accumulation of Ca2+ in the midbrain tissue in the PD environment by measuring its content. Additionally, we have demonstrated a close association between the reduction of dopaminergic neurons, represented by the midbrain region, and ferroptosis by evaluating the iron content, malondialdehyde (MDA) levels, and the protein expression of GPX4 and TH in the tissue. We propose the hypothesis that PD-related inflammation and immune changes can induce neuronal and oligodendrocyte damage through the induction of ferroptosis, thereby further accelerating the progression of PD.

The effective integration of ecosystem services (ESs) and urban growth simulation is crucial for spatial planning decisions that support sustainable and high-quality development. Interactions (i.e., trade-offs, synergies, and irrelevance) generally exist among ESs, however, few studies have been done on the methodology for simulating urban growth that optimizes the synergistic effect of ESs. In this study, the Wuhan metropolitan area was taken as the research area. Four key ESs in 2000, 2010, and 2020: water yield (WY), carbon storage (CS), habitat quality (HQ), and soil retention (SR) were evaluated by using the InVEST model. Then the ordered weighted averaging (OWA) method was applied to optimally allocate ESs trade-offs and identify ecological priority protection areas (EPPAs). Finally, the PLUS model was used to simulate urban growth scenarios under different levels of ESs protection constraints and propose spatial planning strategies. The results revealed the following. (1) From 2000 to 2020, the three ESs (i.e., WY, CS, and HQ) exhibited the spatial distribution pattern with high in the east and low in the west, and higher in the woodland than in built-up areas, except SR, which remained at a weak level throughout the region. (2) During the 20 years, SR and the other three ESs, HQ and CS showed a synergistic relationship; WY exhibited a very weak trade-off with HQ; and WY and CS changed from a very weak trade-off to a weak synergy. (3) Seven ecosystem service patterns (ESPs) were generated, and ESP 5 was compared as the ideal option. The weights of SR, WY, CS, and HQ in this pattern were 0.063, 0.187, 0.313, and 0.437, respectively. (4) By 2030, the built-up areas will exhibit edge expansion and interconnection development trends, with the high-constraint ecological protection scenario as the most compact mode, and the spatial structure of “two districts, one axis, four cities as one” is consistent with the development tendency. Our findings can help to enrich the method of urban growth management oriented by ecological protection, and provide a scientific basis for ecological environment restoration and land use spatial planning practices.

In recent years, China has gradually begun restoring native salt marsh vegetation such as Suaeda salsa (S. salsa) in coastal wetlands that were damaged by the long-term invasion of Spartina alterniflora. Chlorophyll content (Cab), an important indicator of vegetation health, necessitates extensive and long-term monitoring using Sentinel-2. However, due to the influence of betacyanin (Beta), S. salsa exhibits different phenotypes (red and green) under various stress conditions, making remote sensing mechanism studies of this unique vegetation more challenging. In particular, satellite multispectral images are significantly affected by soil background in mixed pixels, making it imperative to mitigate this influence. This study explores the applicability of a recently proposed spectral separation of soil and vegetation (3SV) in Sentinel-2 multispectral and S. salsa vegetation from a remote sensing mechanism perspective, and further improves it. Additionally, a comparative analysis was conducted on the effectiveness of combining 3SV with several mainstream chlorophyll-sensitive indices. The advantages of machine learning algorithms were leveraged to develop a high-precision hybrid semi-empirical model for estimating Cab in different S. salsa phenotypes. The research findings indicate that: (1) The 3SV algorithm, adjusted with slope compensation and B2 and B4 bands, is applicable to green S. salsa scenarios. For red S. salsa scenarios, further adjustment using B2 and B3 bands and coverage fraction is required. (2) The MTCI, MRENDVI, MND, and MNDRE indices combined best with the modified 3SV, significantly reducing the RMSE of the semi-empirical models, especially under wet soil conditions with soil fraction fsoil

White feces syndrome (WFS) is a multifactorial shrimp disease that can cause severe financial losses in Litopenaeus vannamei aquaculture industry. The balance of the intestinal microbiota substantially maintains the health of the host, and dysbiosis is closely associated with diverse diseases. In the present study, intestinal samples were collected from the healthy and WFS-infected shrimp in the same cultured pond to compare the differences in intestinal histology and physiological indices as well as composition and function of intestinal microbiota. The result of intestinal histology revealed that the normal intestinal structure suffered severe damage in WFS-infected shrimp. The expression of antioxidant and immune-related genes like autophagy proteins, antimicrobial peptides were significantly decreased in WFS-infected shrimp. Through the sequencing analysis of the 16S rRNA genes, it was observed that the composition and function of intestinal microbiota had undergone an enormous alteration in WFS-infected shrimp. At phylum level, the abundance of major phylum including Cyanobacteria, Chloroflexi, Patescibacteria and Desulfobacterota were significantly increased, whereas phyla Bacteroidota and Verrucomicrobiota were decreased in WFS-infected shrimp. At the genus level, Cyanobium PCC-6307 and PeM15 were overrepresented in WFS-infected shrimp, and Cyanobium PCC-6307 was a potentially toxic cyanobacteria that could produce cyanotoxins. Functional prediction of intestinal microbiota also revealed that nutrition-related pathways were generally decreased, but disease-related pathways were increased in WFS-infected shrimp. These results illustrated that WFS of Litopenaeus vannamei was closely associated with the composition disorders of intestinal microbiota and hypoimmunity. Additionally, the identified bacterial genus Cyanobium PCC-6307 can be a signature to evaluate the occurrence probability of WFS in shrimp ponds and provide theorical basis for optimal treatments and control methods.

The Monoamine Oxidase-A (MAOA) EcoRV polymorphism (rs1137070) is a unique synonymous mutation (c.1409 T > C) within the MAOA gene, which plays a crucial role in Maoa gene expression and function. This study aimed to explore the relationship between the mouse Maoa rs1137070 genotype and differences in MAOA gene expression. Mice carrying the CC genotype of rs1137070 exhibited a significantly lower Maoa expression level, with an odds ratio of 2.44 compared to the T carriers. Moreover, the wild-type TT genotype of MAOA demonstrated elevated mRNA expression and a longer half-life. We also delved into the significant expression and structural disparities among genotypes. Furthermore, it was evident that different aspartic acid synonymous codons within Maoa influenced both MAOA expression and enzyme activity, highlighting the association between rs1137070 and MAOA. To substantiate these findings, a dual-luciferase reporter assay confirmed that GAC was more efficient than GAT binding. Conversely, the synonymous mutation altered Maoa gene expression in individual mice. An RNA pull-down assay suggested that this alteration could impact the interaction with RNA-binding proteins. In summary, our results illustrate that synonymous mutations can indeed regulate the downregulation of gene expression, leading to changes in MAOA function and their potential association with neurological-related diseases.

ObjectiveThis study aims to identify factors associated with achieving a pathological complete remission (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT).MethodsWe conducted a cohort analysis of 171 LARC patients who underwent curative resection post-nCRT at the First Affiliated Hospital of Guangxi Medical University between January 2015 and December 2021. The data encompassed clinical and pathological information. Univariate and binary logistic regression multivariate analyses were employed to examine the factors influencing pCR achievement after nCRT. Kappa value tests were utilized to compare clinical staging after nCRT with postoperative pathological staging.ResultsPostoperative histopathology revealed that of the 171 patients, 40 (23.4%) achieved TRG 0 grade (pCR group), while 131 (76.6%) did not achieve pCR, comprising 36 TRG1, 42 TRG2, and 53 TRG3 cases. Univariate analysis indicated that younger age (p=0.008), reduced tumor occupation of intestinal circumference (p =0.008), specific pathological types (p=0.011), and lower pre-nCRT CEA levels (p=0.003) correlated with pCR attainment. Multivariate analysis identified these factors as independent predictors of pCR: younger age (OR=0.946, p=0.004), smaller tumor occupation of intestinal circumference (OR=2.809, p=0.046), non-mucinous adenocarcinoma pathological type (OR=10.405, p=0.029), and lower pre-nCRT serum CEA levels (OR=2.463, p=0.031). Clinical re-staging post-nCRT compared to postoperative pathological staging showed inconsistent MRI T staging (Kappa=0.012, p=0.718, consistency rate: 35.1%) and marginally consistent MRI N staging (Kappa=0.205, p=0.001, consistency rate: 59.6%).ConclusionLARC patients with younger age, presenting with smaller tumor circumferences in the intestinal lumen, lower pre-nCRT serum CEA levels, and non-mucinous adenocarcinoma are more likely to achieve pCR after nCRT. The study highlights the need for improved accuracy in clinical re-staging assessments after nCRT in LARC.

Organic electrochemical transistors (OECT) have shown great potential in diverse applications; however, in many OECTs, their slow transient response has thus far limited their practical use. One reason for the slow response is the complex interplay between lateral and vertical ion transport that has so far been poorly understood. In this work, we study the impact of lateral ion transport on OECT transient response, introduce a robust pre-charging method to manipulate the slow lateral ion transport. This approach leads to quicker ion redistribution and improved switching speeds. We show the general utility of pre-charging method in enhancing the switching speeds across various material systems, characterized by both low and high ion mobilities, and across different device architectures, achieving nearly symmetric speeds for both on-switching and off-switching. Moreover, we showcase the efficacy of the pre-charging method in enabling slow OECTs to capture rapid signals in real-world applications. Our findings present a groundbreaking strategy for enhancing the response times of OECT devices and deepening our understanding of the transient mechanisms in OECT device.

Aiming at the current design and construction of reinforced earth retaining wall in which most of the reinforcement laying methods are of equal length, an inverted trapezoidal reinforcement laying method was proposed. Based on the theory of retaining wall displacement zoning and finite-difference Flac3D numerical simulation, a three-dimensional analytical model of reinforced earth retaining wall was established to explore the effects of the three types of reinforced earth retaining wall on the displacements, horizontal earth pressures, reinforcement tensile stresses, and the potential rupture surfaces under different peak accelerations. The results show that with the increase of peak acceleration, the displacement of the retaining wall gradually increases, and under the same load, changing the layout of reinforcement material the lateral horizontal displacement decreases by 9.3%, and the vertical settlement decreases by 5.3%; The horizontal earth pressure of the three forms of retaining wall does not differ much, and the maximum horizontal earth pressure is located in the middle and lower part of the retaining wall; The tensile stress of the reinforcement material transforms from a single-peak type to a bi-peak type along the height of the wall as peak acceleration increases, with the maximum value located in the middle and lower part of the retaining wall; The shape of rupture zone of potential fracture surface filling area is related to the shape of rupture zone of potential fracture surface filling area. The maximum value is located in the middle and lower part of the retaining wall; The shape of the rupture zone in the filling area of the potential rupture surface is related to the deployment method of the reinforcement material. The inverted trapezoidal reinforcement layout has better seismic effect on reinforced soil retaining wall, which provides reference for reinforcement layout of reinforced soil retaining wall in construction design.

Abstract Background Glioblastoma (GBM) is the most common brain tumor with the worst prognosis. Temozolomide is the only first-line drug for GBM. Unfortunately, the resistance issue is a classic problem. Therefore, it is essential to develop new drugs to treat GBM. As an oncogene, Skp2 is involved in the pathogenesis of various cancers including GBM. In this study, we investigated the anticancer effect of AAA237 on human glioblastoma cells and its underlying mechanism. Methods CCK-8 assay was conducted to evaluate IC50 values of AAA237 at 48, and 72 h, respectively. The Cellular Thermal Shift Assay (CETSA) was employed to ascertain the status of Skp2 as an intrinsic target of AAA237 inside the cellular milieu. The EdU-DNA synthesis test, Soft-Agar assay and Matrigel assay were performed to check the suppressive effects of AAA237 on cell growth. To identify the migration and invasion ability of GBM cells, transwell assay was conducted. RT-qPCR and Western Blot were employed to verify the level of BNIP3. The mRFP-GFP-LC3 indicator system was utilized to assess alterations in autophagy flux and investigate the impact of AAA237 on the dynamic fusion process between autophagosomes and lysosomes. To investigate the effect of compound AAA237 on tumor growth in vivo, LN229 cells were injected into the brains of mice in an orthotopic model. Results AAA237 could inhibit the growth of GBM cells in vitro. AAA237 could bind to Skp2 and inhibit Skp2 expression and the degradation of p21 and p27. In a dose-dependent manner, AAA237 demonstrated the ability to inhibit colony formation, migration, and invasion of GBM cells. AAA237 treatment could upregulate BNIP3 as the hub gene and therefore induce BNIP3-dependent autophagy through the mTOR pathway whereas 3-MA can somewhat reverse this process. In vivo, the administration of AAA237 effectively suppressed the development of glioma tumors with no side effects. Conclusion Compound AAA237, a novel Skp2 inhibitor, inhibited colony formation, migration and invasion of GBM cells in a dose-dependent manner and time-dependent manner through upregulating BNIP3 as the hub gene and induced BNIP3-dependent autophagy through the mTOR pathway therefore it might be a viable therapeutic drug for the management of GBM. Graphical Abstract

ABSTRACTThis study is to investigate the therapeutical effect and mechanisms of human-derived adipose mesenchymal stem cells (ADSC) in relieving adriamycin (ADR)-induced nephropathy (AN). SD rats were separated into normal group, ADR group, ADR+Losartan group (20 mg/kg), and ADR + ADSC group. AN rats were induced by intravenous injection with adriamycin (8 mg/kg), and 4 d later, ADSC (2 × 105 cells/mouse) were administrated twice with 2 weeks interval time (i.v.). The rats were euthanized after the 6 weeks’ treatment. Biochemical indicators reflecting renal injury, such as blood urea nitrogen (BUN), neutrophil gelatinase alpha (NGAL), serum creatinine (Scr), inflammation, oxidative stress, and pro-fibrosis molecules, were evaluated. Results demonstrated that we obtained high qualified ADSCs for treatment determined by flow cytometry, and ADSCs treatment significantly ameliorated renal injuries in DN rats by decreasing BUN, Scr and NGAL in peripheral blood, as well as renal histopathological injuries, especially protecting the integrity of podocytes by immunofluorescence. Furthermore, ADSCs treatment also remarkably reduced the renal inflammation, oxidative stress, and fibrosis in DN rats. Preliminary mechanism study suggested that the ADSCs treatment significantly increased renal neovascularization via enhancing proangiogenic VEGF production. Pharmacodynamics study using in vivo imaging confirmed that ADSCs via intravenous injection could accumulate into the kidneys and be alive at least 2 weeks. In a conclusion, ADSC can significantly alleviate ADR-induced nephropathy, and mainly through reducing oxidative stress, inflammation and fibrosis, as well as enhancing VEGF production.

Background: During the acute heart failure (AHF), acute kidney injury (AKI) is highly prevalent in critically ill patients. The occurrence of the latter condition increases the risk of mortality in patients with acute heart failure. The current research on the relationship between nutritional risk and the occurrence of acute kidney injury in patients with acute heart failure is very limited. Methods: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.1) database. We included adult patients with AHF who were admitted to the intensive care unit in the study. Results: A total of 1310 critically ill patients with acute heart failure were included. The AUC of geriatric nutritional risk index (GNRI) (0.694) is slightly superior to that of controlling nutritional status (CONUT) (0.656) and prognostic nutritional index (PNI) (0.669). The Log-rank test revealed a higher risk of acute kidney injury in patients with high nutritional risk (p

IntroductionScreening for effective antiviral compounds from traditional Mongolian medicine not only aids in the research of antiviral mechanisms of traditional medicines, but is also of significant importance for the development of new antiviral drugs targeting influenza A virus. Our study aimed to establish high-throughput, rapid screening methods for antiviral compounds against influenza A virus from abundant resources of Mongolian medicine.MethodsThe use of GFP-based reporter viruses plays a pivotal role in antiviral drugs screening by enabling rapid and precise identification of compounds that inhibit viral replication. Herein, a GFP-based reporter influenza A virus was used to identify potent anti-influenza compounds within traditional Mongolian medicine.ResultsOur study led to the discovery of three active compounds: Cardamonin, Curcumin, and Kaempferide, all of which exhibited significant antiviral properties in vitro. Subsequent analysis confirmed that their effectiveness was largely due to the stimulation of the antiviral signaling pathways of host cells, rather than direct interference with the viral components, such as the viral polymerase.DiscussionThis study showcased the use of GFP-based reporter viruses in high-throughput screening to unearth antiviral agents from traditional Mongolian medicine, which contains rich antiviral compounds and deserves further exploration. Despite certain limitations, fluorescent reporter viruses present substantial potential for antiviral drug screening research due to their high throughput and efficiency.

SOCS (Suppressor of Cytokine Signalling) proteins are intracellular negative regulators that primarily modulate and inhibit cytokine-mediated signal transduction, playing a crucial role in immune homeostasis and related inflammatory diseases. SOCS act as inhibitors by regulating the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, thereby intervening in the pathogenesis of inflammation and autoimmune diseases. Recent studies have also demonstrated their involvement in central immunity and neuroinflammation, showing a dual functionality. However, the specific mechanisms of SOCS in the central nervous system remain unclear. This review thoroughly elucidates the specific mechanisms linking the SOCS-JAK-STAT pathway with the inflammatory manifestations of neurodegenerative diseases. Based on this, it proposes the theory that SOCS proteins can regulate the JAK-STAT pathway and inhibit the occurrence of neuroinflammation. Additionally, this review explores in detail the current therapeutic landscape and potential of targeting SOCS in the brain via the JAK-STAT pathway for neuroinflammation, offering insights into potential targets for the treatment of neurodegenerative diseases.

Neuropsychiatric disorders shorten human life spans through multiple ways and become major threats to human health. Exercise can regulate the estrogen signaling, which may be involved in depression, Alzheimer's disease (AD) and Parkinson's disease (PD), and other neuropsychiatric disorders as well in their sex differences. In nervous system, estrogen is an important regulator of cell development, synaptic development, and brain connectivity. Therefore, this review aimed to investigate the potential of estrogen system in the exercise intervention of neuropsychiatric disorders to better understand the exercise in neuropsychiatric disorders and its sex specific. Exercise can exert a protective effect in neuropsychiatric disorders through regulating the expression of estrogen and estrogen receptors, which are involved in neuroprotection, neurodevelopment, and neuronal glucose homeostasis. These processes are mediated by the downstream factors of estrogen signaling, including N-myc downstream regulatory gene 2 (Ndrg2), serotonin (5-HT), delta like canonical Notch ligand 1 (DLL1), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), etc. In addition, exercise can act on the estrogen response element (ERE) fragment in the genes of estrogenic downstream factors like β-amyloid precursor protein cleavase 1 (BACE1). However, there are few studies on the relationship between exercise, the estrogen signaling pathway, and neuropsychiatric disorders. Hence, we review how the estrogen signaling mediates the mechanism of exercise intervention in neuropsychiatric disorders. We aim to provide a theoretical perspective for neuropsychiatric disorders affecting female health and provide theoretical support for the design of exercise prescriptions.

We report the controlled fabrication of nitrogen doped graphene (NG) nanoplates, which are uniformly decorated with iron nitride (Fe3N) nanoparticles, via ball milling of mixtures of graphite and iron nitrates and the following ammonia annealing. The obtained Fe3N@NG composites demonstrate excellent electrocatalytic activity and durability for oxygen evolution reaction, both of which outperform those of the state-of-the-art iridium oxide catalysts. This may be attributed to nitrogen doping as well as the synergistic effect between Fe3N and graphene nanoplates.

This article presents the scientific outcomes of the 2023 Data Fusion Contest (DFC23) organized by the Image Analysis and Data Fusion Technical Committee of the IEEE Geoscience and Remote Sensing Society. The contest consists of two tracks investigating the fusion of optical and synthetic aperture radar data for: 1) fine-grained roof type classification and 2) height estimation. During the development phase, 1000 people registered for the contest, while at the end 55 and 35 teams competed during the test phase in the two tracks, respectively. This article presents the methods and results obtained by the first and second-ranked teams of each track. In Track 1, both winning teams leveraged pretraining, modern network architectures, model ensembles, and measures to cope with the imbalanced class distribution. The solutions to Track 2 are more diverse and are characterized by modern multitask learning approaches. The data of this contest is openly available to the community for further research, development, and refinement of machine learning methods.

In this paper, a photonic skin sensor based on a balloon-shaped optical fiber structure cascading a Fiber Bragg Grating (FBG) is proposed, which can simultaneously sense pressure and temperature. When the photonic skin feels pressure, the built-in polymer micro-cap is squeezed, causing a change in the radius of the balloon-shaped structure. At the same time, the capillary-enclosed FBG can be used for temperature compensation. The pressure sensitivity of the photon skin sensor can reach 6.556 nm/mN in the range of 0-0.5 mN and the temperature sensitivity can reach -0.192 nm/°C in the range of 30-50 °C. The demodulation of the dual parameter matrix shows that the error rates of pressure and temperature measurements are less than 0.5% and 2.01%, respectively. On this basis, the sensor is applied to robotic arm-assisted puncture experiment detection, and the five states of the puncture process are analyzed. Based on the backpropagation (BP) neural network for repeated training, the results show that its accuracy remains at 98.7%, indicating that the sensor has good robustness. The development of this sensor shows application potential in the field of robotic intelligent skin in the future.

Abstract In this paper, a cost-effective and miniaturized instrument is proposed, which is based on a tunable modulated grating Y-branch (MG-Y) laser for rapid temperature measurement using a Fabry-Perot interferometer (FPI) sensor. The FPI sensor with a 1 463-µm cavity length is a short segment of a capillary tube sandwiched by two sections of single-mode fibers (SMFs). This system has a broad tunable range (1 527 nm–1 567 nm) with a wavelength interval of 8 pm and a tuning rate of 100 Hz. Temperature sensing experiments are carried out to investigate the performance of the system by demodulating the absolute cavity length of the FPI sensor using a cross-correlation algorithm. Experimental results show that the sensor can reach the response time as short as 94 ms with the sensitivity of 802 pm/°C. Benefiting from the homemade and integrated essential electrical circuits, the entire system has the small size, low cost, and practical application potential to be used in the harsh environment for rapid temperature measurement.

Abstract The study of the contamination patterns and characteristics of Sb and As in the soils of the legacy contaminated sites of antimony smelters is important for the redevelopment and utilization of industrial sites. In this study, 13 heavy metals were determined in the soil and plants of an antimony smelter in Gansu Province to study the biogeochemical behavior, health risk, and pollution source. The results showed that the Nemerow index of Sb (728) exceeded the value of As (43.6) by 17.6 times, and the average geoaccumulation index (Igeo) of Sb and As were 10.1 and 1.97, respectively, categorized as extremely and moderately contaminated classes. Compared to As, Sb had a larger proportion of oxidizable fraction and a smaller proportion of reducible fraction (Fe/Mn oxides), suggesting that Sb possessed a higher content of organic matter and sulfide forms. Even though the bioaccumulation factor (BAF) for As was about 10 times higher than that for Sb, the accumulation of Sb in plants was not negligible. For the USEPA model, the mean hazard quotient (HQ) values of As by oral ingestion, dermal absorption, and inhalation accounted for 99.0%, 0.97%, and 0.0002% of the total, and 54.2%, 45.3%, and 0.51% for MEEPRC model, respectively. There were significant positive correlations between Sb, As, Zn, Se, Cd, and Ba (P

Abstract N-acetylserotonin O-methyltransferase (ASMT) is responsible for melatonin biosynthesis. The Asmt gene is located on the X chromosome, and its genetic polymorphism is associated with depression in humans. However, the underlying mechanism remains unclear. Here, we use CRISPR/Cas9 to delete 20 bp of exon 2 of Asmt, and construct C57BL/6J mouse strain with Asmt frameshift mutation (Asmt ft/ft). We show that female Asmt ft/ft mice exhibit anxiety- and depression-like behaviors, accompanied by an obvious structural remodeling of gut microbiota. These behavioral abnormalities are not observed in male. Moreover, female Asmt ft/ft mice show a lower neurobehavioral adaptability to exercise, while wild-type shows a “higher resilience”. Cross-sectional and longitudinal analysis indicates that the structure of gut microbiota in Asmt ft/ft mice is less affected by exercise. These results suggests that Asmt maintains the plasticity of gut microbiota in female, thereby enhancing the neurobehavioral adaptability to exercise.

Abstract Owing to their flexibility and rapid response, grid-connected distributed energy resources (DERs) are wielding growing influence in frequency regulation markets (FRMs). Nevertheless, compared with conventional large-scale generators, small-scale DERs are usually weakly shielded by cyber security measures. This offers attackers the opportunity of disrupting the clearing and settlement of FRMs by manipulating the bid information of DERs. In this paper, the frequency regulation market equilibrium is studied considering the dynamic gaming between attackers and defenders, both of which need the knowledge of FRMs for their interventions. Specifically, a tri-level programming model characterizing the attacker–defender–operator (ADO) interdiction problem in FRMs is developed and then analyzed using a column and constraint generation algorithm, thereby achieving market equilibrium representing the defender's best response to the attacker. The defense strategy in the market equilibrium can attenuate the negative influence of cyber attacks upon the FRMs to the maximum extent. Finally, based on the operating rules of the California Independent System Operator, the FRM process considering the ADO interdiction is simulated and the numerical equilibrium results are presented.

Abstract Oxytocin (OXT), produced and secreted in the paraventricular nucleus and supraoptic nucleus of magnocellular and parvocellular neurons. The diverse presence and activity of oxytocin suggests a potential for this neuropeptide in the pathogenesis and treatment of stress-related neuropsychiatric disorders (anxiety, depression and post-traumatic stress disorder (PTSD)). For a more comprehensive understanding of the mechanism of OXT's anti-stress action, the signaling cascade of OXT binding to targeting stress were summarized. Then the advance of OXT treatment in depression, anxiety, PTSD and the major projection region of OXT neuron were discussed. Further, the efficacy of endogenous and exogenous OXT in stress responses were highlighted in this review. To augment the level of OXT in stress-related neuropsychiatric disorders, current biological strategies were summarized to shed a light on the treatment of stress-induced psychiatric disorders. We also conclude some of the major puzzles in the therapeutic uses of OXT in stress-related neuropsychiatric disorders. Although some questions remain to be resolved, OXT has an enormous potential therapeutic use as a hormone that regulates stress responses.

Abstract In order to realize the efficient development of unconventional oil and gas, the measurement accuracy of wellbore spacing in the drilling of parallel horizontal wells is more and more required. Although the Rotating Magnet Ranging System or Magnetic Guidance Tool is used to achieve a good ranging effect in the drilling of dual horizontal wells, the position measurement of the magnetic sub leads to a large ranging error. A new ranging algorithm for the Two Sensor Packages-Rotating Magnet Ranging System is presented in this paper. The algorithm takes the magnetic signal generated by the rotation of the magnetic sub at a fixed position, the tilt measurement data of the two wells, the length of the magnetic sub, and the distance between the two fluxgate sensors as input parameters to avoid measuring the position of the magnetic sub and to reduce the influence of the degree of non-parallelism and the length of the magnetic sub. The simulation and experiment demonstrate that the inclination and azimuth angles of the two wells have a significant impact on the magnetic ranging results when the ranging well sections are not parallel and that the distance between the bottom of the drill bit and the center of the magnetic sub cannot be ignored. Moreover, the accuracy of the relative distance calculated by this new algorithm can reach 97%, and the error of direction calculation is less than 3°. Applying this algorithm in the field can successfully aid in controlling the spacing of cluster horizontal wells more accurately.

Abstract Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks. Fecal 16S rDNA sequencing and metabolomics were performed. Fecal microbiota transplantation (FMT) was used for the evaluation study. The results demonstrate that deteriorated renal function and gut dysbiosis are found in MN rats, as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness, but both changes were reversed by HP treatment. Reduced gut dysbiosis is correlated with improved colonic integrity and lower endotoxemia in HP-treated rats. HP normalized the abnormal level of fecal metabolites by increasing short-chain fatty acid production and hindering the production of uremic toxin precursors. FMT of HP-treated feces to MN animals moderately reduced endotoxemia and albuminuria. Moreover, major coumarins in HP were only biotransformed into more bioactive 7-hydroxycoumarin by gut microbiota, which strengthened the effect of HP in vivo. Depletion of the gut microbiota partially abolished its renal protective effect. In conclusion, the bidirectional interaction between HP and the gut microbiota contributes to its beneficial effect.

Two-dimensional (2D) ferroelectrics usually exhibit instability or a tendency toward degradation when exposed to the ambient atmosphere, and the mechanism behind this phenomenon remains unclear. To unravel this affection mechanism, we have undertaken an investigation utilizing NH3 and two-dimensional ferroelectric SnS. Herein, the adsorption and desorption of NH3 molecules can reversibly modulate the electrical properties of SnS, encompassing I–V curves and transfer curves. The response time for NH3 adsorption is approximately 1.12 s, which is much quicker than that observed in other two-dimensional materials. KPFM characterizations indicate that air molecules’ adsorption alters the surface potentials of SiO2, SnS, metal electrodes, and contacts with minimal impact on the electrode contact surface potential. Upon the adsorption of NH3 molecules or air molecules, the hole concentration within the device decreases. These findings elucidate the adsorption mechanism of NH3 molecules on SnS, potentially fostering the advancement of rapid gas sensing applications utilizing two-dimensional ferroelectrics.

The Baota District of Yan’an City, located in the Loess Plateau, is an important patriotic education base in China. The region’s fragile geological environment and frequent geological disasters pose significant threats to the production and livelihood of residents. Establishing a landslide traces inventory can provide crucial assistance for studying regional land disaster distribution patterns and implementing disaster prevention and mitigation measures. However, the Baota District has not yet established a comprehensive and detailed landslide traces inventory, resulting in a lack of clear understanding and comprehensive knowledge regarding the threats and impacts of landslide disasters in the area. Therefore, this study employed high-resolution satellite images, applying a human–computer interactive visual interpretation method in conjunction with field survey verifications, to develop the most detailed and comprehensive landslide traces inventory for the Baota District to date. The results indicate that within the 3556 km2 area of the Baota District, there are 73,324 landslide traces, with an average landslide density of 20.62 km-2 and a total landslide area of 769.12 km2, accounting for 21.63% of the total land area. These landslides are relatively evenly distributed throughout the district, with a higher concentration in the east compared to the west. Most of the landslides are small in size. This study can support disaster prevention and mitigation efforts in the Baota District and serve as a reference for establishing landslide inventories in other regions of the Loess Plateau.

Tianjin possesses abundant geothermal resources, and geothermal reinjection is an effective strategy for maintaining the sustainable development and utilization of these resources. However, several issues have arisen in the reinjection of sandstone geothermal reservoirs in the Tianjin area, including a mismatch between the reinjection capacity and effluent capacity, as well as challenges related to continuous reinjection. Therefore, it is crucial to investigate the reinjection of exogenous water into sandstone pore-type geothermal reservoirs. This study focuses on the geothermal reservoir of the Guantao Formation in the Binhai New Area. The surface water treatment process for reinjection into sandstone geothermal reservoirs was determined through water treatment simulation experiments. Additionally, experiments examining the interaction between the reinjected water and reservoir rock were conducted to assess the feasibility of using treated surface water for reinjection into sandstone geothermal reservoirs. The hydrogeochemical response mechanisms and the impact on the reservoir under reinjection conditions were also investigated. The results indicate that a nanofiltration module and tubular microfiltration membrane are essential to ensure the stability of the system. The pH and TDS of water samples decreased after reinjecting mixed water (HHS) into the sandstone reservoir. The hydrochemical type consistently remained Cl-Na. The conventional water chemistry components and trace elements were influenced by the corresponding water–rock reactions. The reservoir minerals exhibited minimal precipitation, primarily consisting of K-feldspar and Fe-dolomite. The minerals produced during the experiment accounted for only 0.08% of the total cuttings’ mass, indicating a negligible impact on the reservoir structure. PHREEQC was employed to simulate the changes in mineral saturation index before and after the reinjection of mixed water and geothermal water, respectively. Notably, similar hydrogeochemical changes were observed in the geothermal fluids. Thus, this study demonstrates the feasibility of reinjecting treated surface water into sandstone geothermal reservoirs from a hydrogeochemical perspective. This research provides valuable insights for the development of external water reinjection projects in hot spring health care units, contributing effectively to the achievement of carbon peaking and carbon neutrality goals.

Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors (MkPs) are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) mainly in CD201−CD48− cells and CD48+ cells separated from the CD150+CD34−Kit+Sca-1+Lin− HSC population of the bone marrow in adult mice. Single-cell colony assay and single-cell transplantation showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average 8 megakaryocytes per colony) than did previously reported MkPs. Single-cell RNA sequencing supported that HSCs give rise to MkPs through MgPs along a Mk differentiation pathway. Single-cell reverse transcription polymerase chain reaction (RT-PCR) analysis showed that MgPs expressed Mk-related genes, but were transcriptionally heterogenous. Clonal culture of HSCs suggested that MgPs are not direct progeny of HSCs. We propose a differentiation model in which HSCs give rise to MgPs which then give rise to MkPs, supporting a classic model in which Mk-lineage commitment takes place at a late stage of differentiation.

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationized bovine serum albumin (c-BSA) into Sprague-Dawley (SD) rats for two weeks, after which mycophenolate mofetil (MMF) and losartan were administered orally. Two and six weeks after ICGN establishment, fecal samples were collected and 16S ribosomal DNA (rDNA) sequencing and untargeted metabolomic were conducted. Fecal microbiota transplantation (FMT) was conducted to determine whether gut normalization caused by MMF and losartan contributed to their renal protective effects. A gradual decline in microbial diversity and richness was accompanied by a loss of renal function. Approximately 18 genera were found to have significantly different relative abundances between the early and later stages, and Marvinbryantia and Allobaculum were markedly upregulated in both stages. Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN, characterized by the overproduction of indole and kynurenic acid, while the serotonin pathway was reduced. Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces. FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes (F/B) ratio but did not improve renal function. These findings indicate that ICGN induces serous gut dysbiosis, wherein an altered tryptophan metabolism may contribute to its progression. MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis, which partially contributed to their renoprotective effects.

To satisfy the requirements of large workspace, high capability, and low inertia demanded by the high precision and high stiffness aerospace equipment, serial manipulator with insufficient intersection joints is proposed in this article based on finite and instantaneous screw theory. Due to the specific topology structure with no intersecting joints at both ends, the explicit solution of forward and inverse kinematics for the serial manipulator with insufficient intersection joints proposed in this article is extremely difficult. Therefore, an analytical method based on finite and instantaneous screw theory is proposed for this serial manipulator, and the explicit kinematic solution is derived in this article. According to particular calculation principle of finite and instantaneous screw theory, the finite motion of this serial manipulator is described. Based on this description, the product of exponentials formula of the kinematics of the serial manipulator with insufficient intersection joints is established on the basic of finite and instantaneous screw theory for the first time, and a novel subproblem is arose during the decomposition of product of exponentials formula. Regarding this issue, an innovative approach to this subproblem is proposed by introducing the new Paden–Kahan subproblem with elimination, and the explicit solution for the inverse kinematics is derived. Finally, the numerical examples are simulated, and the correctness of the method proposed in this article is verified.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.

Introduction: The global headlines have been dominated by the sudden and widespread outbreak of monkeypox, a rare and endemic zoonotic disease caused by the monkeypox virus (MPXV). Genomic composition based machine learning (ML) methods have recently shown promise in identifying host adaptability and evolutionary patterns of virus. Our study aimed to analyze the genomic characteristics and evolutionary patterns of MPXV using ML methods.Methods: The open reading frame (ORF) regions of full-length MPXV genomes were filtered and 165 ORFs were selected as clusters with the highest homology. Unsupervised machine learning methods of t-distributed stochastic neighbor embedding (t-SNE), Principal Component Analysis (PCA), and hierarchical clustering were performed to observe the DCR characteristics of the selected ORF clusters.Results: The results showed that MPXV sequences post-2022 showed an obvious linear adaptive evolution, indicating that it has become more adapted to the human host after accumulating mutations. For further accurate analysis, the ORF regions with larger variations were filtered out based on the ranking of homology difference to narrow down the key ORF clusters, which drew the same conclusion of linear adaptability. Then key differential protein structures were predicted by AlphaFold 2, which meant that difference in main domains might be one of the internal reasons for linear adaptive evolution.Discussion: Understanding the process of linear adaptation is critical in the constant evolutionary struggle between viruses and their hosts, playing a significant role in crafting effective measures to tackle viral diseases. Therefore, the present study provides valuable insights into the evolutionary patterns of the MPXV in 2022 from the perspective of genomic composition characteristics analysis through ML methods.

This study examines the connection between innovation inputs, outputs, and efficiency. Additionally, to establish the connections between the global innovation mechanisms. Furthermore, a closer look at how factors are distinguished and found to be significant based on a country's level of income. To develop the technique in this quantitative research, we utilized panel data from 105 countries and gathered data from the GII, WIPO, and WDI. In light of this, panel-corrected standard errors with robust regression and panel quantile regression techniques were used to obtain the long-run estimations. There were also two methods used to compare the results: two-stage least squares for robustness endogeneity and augmented mean group for cross-section dependency. This research demonstrates that the method is reliable and suggests that countries are open to expansion in innovation inputs, outputs, and efficiency. It also suggests that countries should record problems associated with how well innovations are implemented. In addition, a proper evaluation must be carried out, which includes the development of innovation strategies that consider the varying economic situations of the countries included in this research. Performance in innovation is essential for global success, and this paper investigates the relationship between GII, input, output, and efficiency with creative performance.

Abstract Previous studies have speculated that brain activity directly controls immune responses in lymphoid organs. However, the upstream brain regions that control lymphoid organs and how they interface with lymphoid organs to produce stress-induced anxiety-like behavior remain elusive. Using stressed human participants and rat models, we show that CCL5 levels are increased in stressed individuals compared to controls. Stress-inducible CCL5 is mainly produced from cervical lymph nodes (CLN). Retrograde tracing from CLN identifies glutamatergic neurons in the red nucleus (RN), the activities of which are tightly correlated with CCL5 levels and anxiety-like behavior in male rats. Ablation or chemogenetic inhibition of RN glutamatergic neurons increases anxiety levels and CCL5 expression in the serum and CLNs, whereas pharmacogenetic activation of these neurons reduces anxiety levels and CCL5 synthesis after restraint stress exposure. Chemogenetic inhibition of the projection from primary motor cortex to RN elicits anxiety-like behavior and CCL5 synthesis. This brain-lymph node axis provides insights into lymph node tissue as a stress-responsive endocrine organ.

Abstract Background Immunotherapy has become the fastest‐adopting treatment paradigm for lung cancer with improved survival. By binding with its ligand (inducible T‐cell co‐stimulator and its ligand [ICOSL]), an inducible T‐cell co‐stimulator (ICOS) could contribute to reversing immunosuppression and improving immune response and thus be a potential target for cancer immunotherapy. Methods We selected 54 formalin‐fixed, paraffin‐embedded tumor tissues from cases with stage I–III lung adenocarcinoma cancer. Immunohistochemical expression of ICOS and ICOSL was evaluated. The correlation with clinical parameters in Chinese patients was also compared with TCGA results. Results The positive rates of ICOS and ICOSL were 68% and 81.5%, respectively, in lung tumor tissues. Of these, 9 cases had a low expression of ICOS, and 22 cases had a high expression of ICOS; ICOSL expression was low in 20 cases and high in 24 cases. According to the International Association for the Study of Lung Cancer (8th edition), phase I lesions were detected in 21 cases, phase II lesions in 15 cases, and phase III lesions in 18 cases. The median survival time of all patients was 44.5 months, and the median disease‐free survival was 32 months. Univariate analysis showed that the factors significantly associated with overall survival were tumor size, regional lymph node involvement, stage, and expression level of ICOS/ICOSL. Survival analysis using log‐rank test indicated that the lower ICOS+ cell infiltration may predict poor prognosis, whereas lower ICOSL protein expression may be associated with better prognosis, but ICOSL data need further validation in larger samples due to inconsistency in TCGA mRNA prediction. Conclusion ICOS/ICOSL might be associated with prognosis of lung cancer, and ICOS and its ligand may be potential therapeutic targets in non‐small cell lung cancer.

Using DTAW-8000 rock high-pressure dynamic test system and acoustic emission technology, through uniaxial compression tests with different dynamic load disturbance frequencies, the relationship between fracture characteristics and acoustic emission characteristic parameters of impact tendency coal under dynamic and static combined loading is studied, the whole process of impact tendency coal compression damage is analyzed, and the damage evolution model is established. The results show that with the increase of dynamic load disturbance frequency, the main fracture angle of coal rock with impact tendency decreases first and then increases, and the stress and strain both decrease; the development and expansion process of internal fractures in coal rock with impact tendency are closely related to acoustic emission signal, the cumulative number of acoustic emission ringing changes in the whole process of coal rock compression can be roughly divided into stable stage, sudden increase stage and slow increase until failure stage; the trend of coal and rock damage evolution model is consistent with the test data; the frequency of dynamic load disturbance is the main factor that affects the time history of coal rock fracture in the stage of slow-rapid growth of coal rock damage.

The coronavirus disease 2019 (COVID-19) pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a worldwide impact. However, detailed data on the potential aerosol transmission of SARS-CoV-2 in real-world and controlled laboratory settings remain sparse. During the COVID-19 pandemic in Shanghai, China in 2022, samples were collected in a Fangcang shelter hospital, a large-scale temporary hospital rapidly built by converting the existing National Exhibition and Convention Center (Shanghai) into a health care facility. Aerosol samples at different sites and intervals around patients and in public areas, surface samples, and pharyngeal swab samples from corresponding patients were included. Samples were tested for SARS-CoV-2 using real-time quantitative polymerase chain reaction (RT-qPCR) assays, followed by sequencing if the cycle threshold (Ct) value was < 30. The positivity rate for SARS-CoV-2 in aerosol samples was high in contaminated zones (37.5%, 104/277), especially around the bed (41.2%, 68/165) and near ventilation inlets (45.2%, 14/31). The prevalence of SARS-CoV-2 around the bed, public areas, and air inlets of exhaust vents fluctuated and was closely related to the positivity rate among patients at corresponding sampling sites. Some surface samples of different personal protective equipment from medical staff had high positivity rates. Sixty sequences of joined ORF1ab and spike genes obtained from sixty samples represented two main clusters of Omicron SARS-CoV-2. There was consistency in virus sequences from the same patient and their environment, and the detected virus sequences matched those of virus strains in circulation during the collection periods, which indicated a high likelihood of cross-contamination in the Fangcang shelter hospital. In summary, the results provide a quantitative and real landscape of the aerosol transmission of SARS-CoV-2 and a patient-centered view of contamination in large and enclosed spaces and offer a useful guide for taking targeted measures to avoid nosocomial infections during the management of SARS-CoV-2 or other respiratory virus diseases in a Fangcang shelter hospital.

Abstract Background Breast cancer (BC) is the leading cause of morbidity and the second leading cause of death among female malignant tumors. Although available drugs have been approved for the corresponding breast cancer subtypes (ER-positive, HER2+) currently, there are still no effective targeted drugs or treatment strategies for metastatic breast cancer or triple-negative breast cancer that lack targets. Therefore, it is urgent to discover new potential targets. ERCC6L is an essential protein involved in chromosome separation during cell mitosis. However, the effect of ERCC6L on the tumorigenesis and progression of breast cancer is unclear. Methods and results Here, we found that ERCC6L was highly expressed in breast cancer, especially in TNBC, which was closely related to poor outcomes of patients. An ERCC6L conditional knockout mouse model was first established in this study, and the results confirmed that ERCC6L was required for the development of the mammary gland and the tumorigenesis and progression of mammary gland cancers. In in vitro cell culture, ERCC6L acted as a tumor promoter in the malignant progression of breast cancer cells. Overexpression of ERCC6L promoted cell proliferation, migration and invasion, while knockdown of ERCC6L caused the opposite results. Mechanistically, ERCC6L accelerated the cell cycle by regulating the G2/M checkpoint signalling pathway. Additionally, we demonstrated that there is an interaction between ERCC6L and KIF4A, both of which are closely related factors in mitosis and are involved in the malignant progression of breast cancer. Conclusions We first demonstrated that ERCC6L deficiency can significantly inhibit the occurrence and development of mammary gland tumors. ERCC6L was found to accelerate the cell cycle by regulating the p53/p21/CDK1/Cyclin B and PLK/CDC25C/CDK1/Cyclin B signalling pathways, thereby promoting the malignant progression of breast cancer cell lines. There was a direct interaction between KIF4A and ERCC6L, and both are closely associated with mitosis and contribute to growth and metastasis of breast tumor. To sum up, our results suggest that ERCC6L may be used as a promising target for the treatment of BC.