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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.

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.

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.

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

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

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 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.

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.

The extant research on deviant workplace behavior has mainly examined the consequences of such behavior from a “victim-centric” perspective, while ignoring the psychological and behavioral responses of the employees who engaged in it. Drawing upon moral cleansing theory, we adopt a “victimizer-centric” perspective and contend that employees experience moral deficits after engaging in deviant workplace behavior, which consequently lead to subsequent proactive behavior. We also propose that the indirect relationship between deviant workplace behavior and proactive behavior is contingent upon individuals’ moral courage. Specifically, employees with high moral courage are more inclined to perform subsequent proactive behavior upon perceiving a moral deficit than those with low moral courage. Our hypotheses are supported by empirical data from an experimental study involving 128 participants in the United Kingdom (Study 1) and a multi-wave survey-based field study with a sample of 180 employees conducted in the United States (Study 2). Our research provides contributions to the literature on deviant workplace behavior by demonstrating how and when deviant workplace behavior can lead to subsequent compensatory behavior, as well as practical insights for both employees and organizations.

Immune checkpoint proteins have become recent research hotspots for their vital role in maintaining peripheral immune tolerance and suppressing immune response function in a wide range of tumors. Therefore, investigating the immunomodulatory functions of immune checkpoints and their therapeutic potential for clinical use is of paramount importance. The immune checkpoint blockade (ICB) is an important component of cancer immunotherapy, as it targets inhibitory immune signaling transduction with antagonistic antibodies to restore the host immune response. Anti-programmed cell death-1 (PD-1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies are two main types of widely used ICBs that drastically improve the survival and prognosis of many patients with cancer. Nevertheless, the response rate of most cancer types remains relatively low due to the drug resistance of ICBs, which calls for an in-depth exploration to improve their efficacy. Accumulating evidence suggests that immune checkpoint proteins are glycosylated in forms of N-glycosylation, core fucosylation, or sialylation, which affect multiple biological functions of proteins such as protein biosynthesis, stability, and interaction. In this review, we give a brief introduction to several immune checkpoints and summarize primary molecular mechanisms that modulate protein stability and immunosuppressive function. In addition, newly developed methods targeting glycosylation on immune checkpoints for detection used to stratify patients, as well as small-molecule agents disrupting receptor–ligand interactions to circumvent drug resistance of traditional ICBs, in order to increase the clinical efficacy of immunotherapy strategies of patients with cancer, are also included to provide new insights into scientific research and clinical treatments.

Urban agglomerations are important spatial carriers for regional economic development, but sustained urban expansion has triggered a series of issues such as conflicts between “people and land” and “built-up areas and green spaces”. However, many studies have rarely incorporated spatiotemporal patterns and driving mechanism into scenario simulation of urban growth, and has also overlooked subsequent discussions on the specific integration of simulation results with spatial planning. Considering the case of Min Delta Region, this study analyzes the spatiotemporal evolution of urban expansion based on multi-source data and explore the influential driving mechanism using Random forest algorithm. A combination of Markov and FLUS models was used to dynamically simulate future urban growth patterns. The results showed that 1) From 1995 to 2015, the urban expansion increased by 2.26 times, showing a trend of first accelerating and then slowing down. It was also discovered that there is an anisotropy toward expansion in the trajectory of urban growth. 2) With marginal increase and enclave increase, general urban expansion was observed to be changing from diffusion to agglomeration, and the urban expansion hotspots mainly located in the southeast coastal area. 3) Humanistic links, geographic position, social and economic considerations all played a role in the development of the Min Delta region, and can be summarized as the “four forces” driving mechanism model. 4) By 2035, the trend of continuous development with the Min Delta built-up area as the main body will be basically formed, and incorporating ecological restrictions can effectively restrain urban growth's encroachment into ecological spaces. Based on the simulation results, Min Delta region gradually showing a spatial structure evolution trend from the single core to the dual core mode, and then to the multi-center and networked mode. This study would serve as a multi-angle decision-making reference for regional spatial and ecological protection planning and urban growth management, and as a scientific foundation for high-quality development planning in the region.

Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker that can define the risk of recurrence after curative-intent surgery for patients with colorectal cancer (CRC). However, beyond the predictive power of postoperative ctDNA detection, the efficacy and potential limitations of ctDNA detection urgently need to be fully elucidated in a large cohort of CRC. Objectives: To define potentially cured CRC patients through ctDNA monitoring following surgery. Design: A prospective, multicenter, observational study. Methods: We enrolled 309 patients with stages I–IV CRC who underwent definitive surgery. Tumor tissues were sequenced by a custom-designed next-generation sequencing panel to identify somatic mutations. Plasma was analyzed using a ctDNA-based molecular residual disease (MRD) assay which integrated tumor-genotype-informed and tumor-genotype-naïve ctDNA analysis. The turnaround time of the assay was 10–14 days. Results: Postoperative ctDNA was detected in 5.4%, 13.8%, 15%, and 30% of patients with stage I, II, III, and IV disease, respectively, and in 17.5% of all longitudinal samples. Patients with positive postsurgery MRD had a higher recurrence rate than those with negative postsurgery MRD [hazard ratio (HR), 13.17; p < 0.0001], producing a sensitivity of 64.6%, a specificity of 94.8%, a positive predictive value (PPV) of 75.6%, and a negative predictive value (NPV) of 91.5%. Furthermore, patients with positive longitudinal MRD also had a significantly higher recurrence rate (HR, 14.44; p < 0.0001), with increased sensitivity (75.0%), specificity (94.9%), PPV (79.6%), and NPV (93.4%). Subgroup analyses revealed that adjuvant therapy did not confer superior survival for patients with undetectable or detectable MRD. In addition, MRD detection was less effective in identifying lung-only and peritoneal metastases. Conclusion: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and microsatellite instability status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.

Commercial vehicle disk brakes operate at a high-temperature and in a heavy-load environment within the braking system. The primary cause of failure is the cracking of the brake disk. In order to study its fatigue damage and service life, a finite element model of disk brake fatigue life was established, and thermal stress coupling simulation analysis was carried out from a practical problem. Based on the temperature and stress fields of the brake disk under emergency braking conditions obtained from the simulation results, the effects of vehicle load, initial speed, temperature, and other factors on brake fatigue life are explored. The fatigue life of the hazardous node can be calculated using the Manson–Coffin model, and then the strain–life (ɛ–N) curve of the material can be fit at high temperature. The fatigue life of brake disks was predicted using the fatigue analysis software FE-SAFE and verified by testing. The results showed that the maximum stress on the surface of the disk brake was the same as the area of the minimum fatigue life, accurately analyzing the fatigue life of the region and predicting the location of fatigue cracks. The results of the research can provide a reference for the design of disk brake engineering and fatigue failure.

The nitrogen vacancy (NV) color centers are a solid-state quantum system with the ability to maintain long coherence times at room temperatures. NV centers have potential applications in quantum detection, which necessitates their positioning at minimal distances from surfaces. However, the existing methods for fabricating NV centers are cumbersome, expensive, and difficult to control. This study investigates the etching mechanism of transition metals on diamond under plasma conditions and develops a method for producing shallow NV centers on the surface of high pressure and high temperature diamond. Our proposed method enables the production of shallow NV centers below the surface in the longitudinal direction, while simultaneously allowing precise control over the lateral distribution. Moreover, the operating costs associated with our technique are significantly lower than those of ion implantation and electron irradiation. This research contributes to the advancement of iron-etching diamond processing technology, and the proposed method facilitates the more portable preparation of shallow color centers in specific regions, enabling the realization of locally controllable and scalable coupled quantum systems.

Backgrounds: Hemorrhagic transformation (HT) is a complication after stroke and is associated with increased mortality and disability. Hyperglycemia is a risk factor for HT incidence and seriously affects the treatment of stroke. There are no effective drugs to cure HT in the clinic. The Xiaoshuan Tongluo effective component group (XECG) is a Chinese medicine formula reconstituted by active ingredients, which is clinically used for the treatment of stroke. However, the roles of XECG in hyperglycemia-enhanced HT are not clear. This study aims to evaluate the effects of XECG on hyperglycemia-enhanced HT and explore the potential mechanisms. Methods: In this study, a hyperglycemia-induced HT model was used. XECG (100, 200, 400 mg·kg−1) was orally administered for 5 days before the operation, and the incidence of HT was evaluated. Microglia polarization and related signaling pathways were measured to clarify the mechanisms of XECG on hyperglycemia-induced HT. Results: Our results revealed that pretreatment with XECG alleviated neurological deficits and BBB disruption and improved the incidence and severity of HT enhanced by hyperglycemia. Further studies confirmed that XECG regulated microglial polarization by inhibiting the M1 phenotype and promoting the M2 phenotype and inhibited the activation of the HMGB1-RAGE-NF-κB signaling pathway. Conclusions: These results suggested that pretreatment with XECG alleviated hyperglycemia-enhanced HT. XECG may be a potential drug for the treatment of HT.

AbstractThe renal interstitial fibrosis contributes to the progression and deterioration of diabetic nephropathy (DN). Long noncoding RNA taurine-up-regulated gene 1 (TUG1) in kidneys may be down-regulated by hyperglycemia. We aim to explore its role in tubular fibrosis caused by high glucose and the possible target genes of TUG1. In this study, a streptozocin-induced accelerated DN mouse model and a high glucose-stimulated HK-2 cells model was established to evaluate TUG1 expression. Potential targets of TUG1 were analyzed by online tools and confirmed by luciferase assay. A rescue experiment and gene silencing assay were used to investigate whether TUG1 plays its regulation role via miR-145-5p/dual-specificity phosphatase 6 (DUSP6) in HK2 cells. The effects of TUG1 on inflammation and fibrosis in high glucose treated tubular cells were evaluated by in vitro study, as well as in vivo DN mice model through AAV-TUG1 delivery. Results showed TUG1was downregulated in HK2 cells incubated with high glucose while miR-145-5p was upregulated. Overexpression of TUG1 alleviated renal injury by suppressing inflammation and fibrosis in vivo. Overexpression of TUG1 inhibited HK-2 cell fibrosis and relieved the inflammation. A mechanism study demonstrated that TUG1 directly sponged to miR-145-5p, and DUSP6 was identified as a target downstream of miR-145-5p. In addition, miR-145-5 overexpression and DUSP6 inhibition countervailed the impacts of TUG1. Our findings revealed that TUG1 overexpression alleviates kidney injury in DN mice and decreases the inflammatory response and fibrosis of high glucose-stimulated HK-2 cells via miR-145-5p/DUSP6 axis.

Abstract To explore the strain rate effect of deformation and failure of impact prone coal rock, uniaxial compression tests and triaxial compression tests with different strain rates were carried out. The mechanical properties and impact tendency of impact-prone coal rock were studied, and the energy evolution law and pre-peak energy self-promotion-inhibition mechanism of impact-prone coal rock were obtained. The results show that with the increase of strain rate, the peak strength of coal rock under uniaxial compression decreases gradually, and the peak strength of coal rock under triaxial compression increases first and then decreases, and the impact tendency of coal rock increases first and then decreases. The energy evolution of coal rock under uniaxial compression is mainly divided into four stages: initial energy damage, energy hardening, energy softening and failure. With the increase of strain rate, the total energy and elasticity at the peak point of coal rock under uniaxial compression decrease gradually, and the total energy, elastic energy and dissipation energy at the peak point under triaxial compression increase first and then decrease. The elastic energy promotion coefficient of impact-prone coal rock is much larger than the inhibition coefficient, and the increase of strain rate will promote the generation of elastic energy inside coal rock. The research results can provide reference for the prevention and early warning of dynamic disasters of coal and rock mass with impact tendency.

Digestive system cancer and COVID-19 significantly affect the digestive system, but the mechanism of interaction between COVID-19 and the digestive system cancers has not been fully elucidated. We downloaded the gene expression of COVID-19 and seven digestive system cancers (oral, esophageal, gastric, colorectal, hepatocellular, bile duct, pancreatic) from GEO and identified hub differentially expressed genes. Multiple verifications, diagnostic efficacy, prognostic analysis, functional enrichment and related transcription factors of hub genes were explored. We identified 23 common DEGs for subsequent analysis. CytoHubba identified nine hub genes (CCNA2, CCNB1, CDKN3, ECT2, KIF14, KIF20A, KIF4A, NEK2, TTK). TCGA and GEO data validated the expression and excellent diagnostic and prognostic ability of hub genes. Functional analysis revealed that the processes of cell division and the cell cycle were essential in COVID-19 and digestive system cancers. Furthermore, six related transcription factors (E2F1, E2F3, E2F4, MYC, TP53, YBX1) were involved in hub gene regulation. Via in vitro experiments, CCNA2, CCNB1, and MYC expression was verified in 25 colorectal cancer tissue pairs. Our study revealed the key biomarks and common pathogenesis of digestive system cancers and COVID-19. These may provide new ideas for further mechanistic research.

Harmful algal blooms in eutrophic lakes pose significant challenges to the aquatic environment. Aerobic composting is an effectively method for processing and reusing dewatered algal sludge. The fungal communities are the main driver of composting. However, their relationship with carbon loss and the humification process during algal sludge composting remains unclear. In this study, the succession of fungal communities in algal sludge composting was investigated via internal transcribed spacer (ITS) rRNA amplicon sequencing analysis. Overall, no significant differences were observed with the α-diversity of fungal communities at different stages. The composition of the fungal communities changed significantly before and after compost maturation and became more stable after the compost maturation. Redundancy analysis showed that the fungal communities were significantly correlated with physicochemical properties, including humic acid (HA)/fulvic acid (FA), temperature, pH, humic acid, microcystins, and CO2. The co-occurrence network showed that different fungal community modules had different relationships with physicochemical properties. Structural equation modeling further revealed that different metabolic or transformation processes may be mainly driven by different fungi modules. The microcystin degradation, carbon loss, and humification during composting were mainly mediated by fungal communities which were mainly influenced by temperature. Humification was influenced not only by fungal communities but also by the microcystin levels. These results show that changes in the fungal community composition and interaction and their relationship with physicochemical properties could represent a useful guide for optimizing the composting process.

The protective effects of hydrogen sulfide (H2S) against ischemic brain injury and its role in promoting angiogenesis have been established. However, the specific mechanism underlying these effects remains unclear. This study is designed to investigate the regulatory impact and mechanism of H2S on VEGFR2 phosphorylation. Following expression and purification, the recombinant His-VEGFR2 protein was subjected to LC-PRM/MS analysis to identify the phosphorylation sites of VEGFR2 upon NaHS treatment. Adenovirus infection was used to transfect primary rat brain artery endothelial cells (BAECs) with the Ad-VEGFR2WT, Ad-VEGFR2Y797F, and Ad-VEGFR2S799A plasmids. The expression of VEGFR2 and recombinant Flag-VEGFR2, along with Akt phosphorylation, cell proliferation, and LDH levels, was assessed. The migratory capacity and tube-forming potential of BAECs were assessed using wound healing, transwell, and tube formation assays. NaHS notably enhanced the phosphorylation of VEGFR2 at Tyr797 and Ser799 sites. These phosphorylation sites were identified as crucial for mediating the protective effects of NaHS against hypoxia–reoxygenation (H/R) injury. NaHS significantly enhanced the Akt phosphorylation, migratory capacity, and tube formation of BAECs and upregulated the expression of VEGFR2 and recombinant proteins. These findings suggest that Tyr797 and Ser799 sites of VEGFR2 serve as crucial mediators of H2S-induced pro-angiogenic effects and protection against H/R injury.

The achievement of the low Gilbert damping parameter in spin dynamic modulation is attractive for spintronic devices with low energy consumption and high speed. Metallic ferromagnetic alloy Co-Fe-B is a possible candidate due to its high compatibility with spintronic technologies. Here, we report thickness-dependent damping and soft magnetism in Co-Fe-B films sandwiched between two non-magnetic layers with Co-Fe-B films up to 50 nm thick. A non-monotonic variation of Co-Fe-B film damping with thickness is observed, which is in contrast to previously reported monotonic trends. The minimum damping and the corresponding Co-Fe-B thickness vary significantly among the different non-magnetic layer series, indicating that the structure selection significantly alters the relative contributions of various damping mechanisms. Thus, we developed a quantitative method to distinguish intrinsic from extrinsic damping via ferromagnetic resonance measurements of thickness-dependent damping rather than the traditional numerical calculation method. By separating extrinsic and intrinsic damping, each mechanism affecting the total damping of Co-Fe-B films in sandwich structures is analyzed in detail. Our findings have revealed that the thickness-dependent damping measurement is an effective tool for quantitatively investigating different damping mechanisms. This investigation provides an understanding of underlying mechanisms and opens up avenues for achieving low damping in Co-Fe-B alloy film, which is beneficial for the applications in spintronic devices design and optimization.

Bovine parainfluenza virus type 3 (BPIV-3) is one of the major pathogens of the bovine respiratory disease complex (BRDC). BPIV-3 surveillance in China has been quite limited. In this study, we used PCR to test 302 cattle in China, and found that the positive rate was 4.64% and the herd-level positive rate was 13.16%. Six BPIV-3C strains were isolated and confirmed by electron microscopy, and their titers were determined. Three were sequenced by next-generation sequencing (NGS). Phylogenetic analyses showed that all isolates were most closely related to strain NX49 from Ningxia; the genetic diversity of genotype C strains was lower than strains of genotypes A and B; the HN, P, and N genes were more suitable for genotyping and evolutionary analyses of BPIV-3. Protein variation analyses showed that all isolates had mutations at amino acid sites in the proteins HN, M, F, and L. Genetic recombination analyses provided evidence for homologous recombination of BPIV-3 of bovine origin. The virulence experiment indicated that strain Hubei-03 had the highest pathogenicity and could be used as a vaccine candidate. These findings apply an important basis for the precise control of BPIV-3 in China.

Abstract Background Colorectal cancer (CRC) is the third leading cause of cancer‐related deaths worldwide. Studies have shown that the DNA damage response (DDR) mutation is strongly associated with microsatellite instability (MSI) status and is an indication for patients with CRCs receiving immune checkpoint inhibitor (ICI) treatment. However, DDR mutation in microsatellite stable (MSS) CRC remains unclear. Methods In this study, Fisher's exact test, Student'st‐test, Wilcoxon rank‐sum test and Cox proportional hazards regression model were performed, and a p value of