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Abstract Protein tyrosine phosphatase SHP2 activates RAS signaling, which is a novel target for colorectal cancer (CRC) therapy. However, SHP2 inhibitor monotherapy is ineffective for metastatic CRC and a combination therapy is required. In this study, we aimed to improve the antitumor efficacy of SHP2 inhibition and try to explore the resistance mechanism of SHP2 inhibitor. Results showed that WWP1 promoted the proliferation of CRC cells. Genetic or pharmacological inhibition of WWP1 enhanced the effect of SHP2 inhibitor in suppressing tumor growth in vitro and in vivo. WWP1 may mediate feedback reactivation of AKT signaling following SHP2 inhibition. Furthermore, nomogram models constructed with IHC expression of WWP1 and SHP2 greatly improved the accuracy of prognosis prediction for patients with CRC. Our findings indicate that WWP1 inhibitor I3C can synergize with SHP2 inhibitor and is expected to be a new strategy for clinical trials in treating advanced CRC patients.

Abstract Background Methylenetetrahydrofolate reductase (MTHFR) is essential for the metabolism of folic acid and homocysteine. The MTHFR C677T polymorphism is associated with several disorders. Our study aims to explore the geographical distributions of the MTHFR C677T polymorphism of women in China and how migration affected the polymorphism in Suzhou. Methods A total of 7188 women of reproductive age were recruited in Suzhou of the study. Subjects were classified according to their native places after data extraction. MTHFR C677T gene polymorphisms were detected by quantitative PCR with genomic DNA isolated from blood samples. Results The frequencies of the 677T allele and 677TT genotype were higher in northern China than that in southern China and decreased in geographical gradients from north to south. The frequencies were considerably higher in the migrant population than that in the indigenous population of Suzhou. The migrant population have gradually changed the prevalence in Suzhou. Conclusions Our study suggested that the prevalence of MTHFR C677T polymorphisms among women varied across different geographical regions in Chinese Han populations. The 677T allele frequencies of the northern populations were significantly higher than those of the southern populations. The migrant population gradually changed the prevalence of the MTHFR C677T polymorphism in Suzhou.

The healing of large skin defects remains a significant challenge in clinical settings. The lack of epidermal sources, such as autologous skin grafting, limits full-thickness skin defect repair and leads to excessive scar formation. Skin organoids have the potential to generate a complete skin layer, supporting in-situ skin regeneration in the defect area. In this study, skin organoid spheres, created with human keratinocytes, fibroblasts, and endothelial cells, showed a specific structure with a stromal core surrounded by surface keratinocytes. We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid. Moreover, the 3D bioprinted skin organoid was customized to match the size and shape of the wound site, facilitating convenient implantation. When applied to full-thickness skin defects in immunodeficient mice, the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration, epithelialization, vascularization, and inhibition of excessive inflammation. The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes, offering a novel treatment strategy to address large-area skin defects.

Abstract NOTCH receptor 3 (NOTCH3) is known to regulate the transcription of oncogenes or tumor suppressor genes, thereby playing a crucial role in tumor development, invasion, maintenance, and chemotherapy resistance. However, the specific mechanism of how NOTCH3 drives immune infiltration in gastrointestinal cancer remains uncertain. The expression of NOTCH3 was analyzed through Western blot, PCR, Oncomine database, and the Tumor Immune Estimation Resource (TIMER) site. Kaplan–Meier plotter, PrognoScan database, and gene expression profile interactive analysis (GEPIA) were used to assess the impact of NOTCH3 on clinical prognosis. The correlation between NOTCH3 expression and immune infiltration gene markers was investigated using TIMER and GEPIA. NOTCH3 was found to be commonly overexpressed in various types of gastrointestinal tumors and was significantly associated with poor prognosis. Furthermore, the expression level of NOTCH3 showed a significant correlation with the tumor purity of gastrointestinal tumors and the extent of immune infiltration by different immune cells. Our findings suggest that NOTCH3 may act as a crucial regulator of tumor immune cell infiltration and can serve as a valuable prognostic biomarker in gastrointestinal cancers.

Abstract Colorectal cancer (CRC) remains a major global cause of cancer-related mortality, lacking effective biomarkers and therapeutic targets. Revealing the critical pathogenic factors of CRC and the underlying mechanisms would offer potential therapeutic strategies for clinical application. G protein signaling (RGS) protein family modulators play essential role within regulating downstream signaling of GPCR receptors, with function in cancers unclear. Our study focused on the expression patterns of RGS proteins in CRC, identifying Regulator of G protein signaling 16 (RGS16) as a prospective diagnostic and therapeutic target. Analyzing 899 CRC tissues revealed elevated RGS16 levels, correlating with clinicopathological features and CRC prognosis by immunohistochemistry (IHC) combined with microarray. We confirmed the elevated RGS16 protein level in CRC, and found that patients with RGS16-high tumors exhibited decreased disease-specific survival (DSS) and disease-free survival (DFS) compared to those with low RGS16 expression. Functional assays demonstrated that RGS16 promoted the CRC progression, knockdown of RGS16 led to significantly increased apoptosis rates of CRC in vitro and in vivo. Notably, we also confirmed these phenotypes of RGS16 in organoids originated from resected primary human CRC tissues. Mechanistically, RGS16 restrained JNK/P38-mediated apoptosis in CRC cells through disrupting the recruitment of TAB2/TAK1 to TRAF6. This study provides insights into addressing the challenges posed by CRC, offering avenues for clinical translation.

Abstract Among middle‐aged and older people, balanced and nutritious diets are the foundation for maintaining bone health and preventing osteoporosis. This study is aimed at investigating the link between dietary folic acid intake and the risk of osteoporosis among middle‐aged and older people. A total of 20,686 people from the National Health and Nutritional Examination Survey (NHANES) 2007–2010 are screened and included, and 5312 people aged ≥45 years with integral data are ultimately enrolled in evaluation. Demographics and dietary intake‐related data are gathered and analyzed, and the odds ratio (OR) and 95% confidence interval (CI) of each tertile category of dietary folic acid intake and each unit increase in folic acid are assessed via multivariate logistic regression models. On this basis, the receiver operating characteristic (ROC) curve is used to identify the optimal cutoff value of dietary folic acid intake for indicating the risk of osteoporosis. Of 5312 people with a mean age of 62.4 ± 11.0 years old, a total of 513 people with osteoporosis are screened, and the dietary folic acid intake amount of the osteoporosis group is significantly lower than that of the non‐osteoporosis group (p

Abstract Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.

Abstract Purpose We aimed to investigated the influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Methods This was a prospective cohort design study. High-performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentration. First-generation sequencing was performed to detect gene polymorphisms. Indicators of liver function were detected at least once before and after voriconazole therapy. Results Forty-one patients were included in this study, among which, 15 patients (36.6%) had voriconazole-induced liver injury. The proportion of voriconazole trough concentration > 5.5 μg·mL−1 patients within the DILI group (40.0%) was significantly higher compared to the control group (15.4%) (p 0.05). Conclusion There was a significant correlation between voriconazole-induced liver injury and voriconazole trough concentration in high-risk Uygur pediatric patients with allogeneic HSCT.

Ammonium dihydrogen phosphate (ADP) is a nitrogen-phosphorus-based inorganic flame retardant that is environmentally friendly and non-toxic. Wood treated with ADP has enhanced thermal stability and flame retardancy. Compounding ADP with Acid Red 3R dye further improves the decorative effect of the wood on the basis of excellent flame retardancy, resulting in a kind of dyeing and flame retardant multifunctionalized wood. Single-factor tests were designed to investigate the effects of flame retardant concentration, dye concentration, temperature, and time on three evaluation indexes: dye-uptake, color difference, and oxygen index, respectively. Through SEM and FTIR analysis, it was found that after the wood was simultaneously treated with flame retardant and dye, the two additives were aggregated in the grain pores of the cell wall by a simple physical combination. They did not undergo a chemical reaction. TG analysis showed that fire-retardant dyed wood had good thermal stability, which can delay the thermal degradation of wood and increase the residual charcoal rate of wood. XRD showed that the crystallinity of fire-retardant dyed wood increased compared to untreated wood. Through cone calorimetric test, it is found that flame retardant dyed veneer had excellent flame retardancy.

Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.

IntroductionIn recent years, nitrogen deposition has constantly continued to rise globally. However, the impact of nitrogen deposition on the soil physicochemical properties and microbial community structure in northern Guangxi is still unclear.MethodsAlong these lines, in this work, to investigate the impact of atmospheric nitrogen deposition on soil nutrient status and bacterial community in subtropical regions, four different nitrogen treatments (CK: 0 gN m–2 a–1, II: 50 gN m–2 a–1, III: 100 gN m–2 a–1, IV: 150 gNm– 2 a–1) were established. The focus was on analyzing the soil physical and chemical properties, as well as bacterial community characteristics across varying nitrogen application levels.Results and discussionFrom the acquired results, it was demonstrated that nitrogen application led to a significant decrease in soil pH. Compared with CK, the pH of treatment IV decreased by 4.23%, which corresponded to an increase in soil organic carbon and total nitrogen. Moreover, compared with CK, the soil organic carbon of treatment IV increased by 9.28%, and the total nitrogen of treatment IV increased by 19.69%. However, no significant impact on the available nitrogen and phosphorus was detected. The bacterial diversity index first increased and then decreased with the increase of the nitrogen application level. The dominant phylum in the soil was Acidobacteria (34.63–40.67%), Proteobacteria, and Chloroflexi. Interestingly, the abundance of Acidobacteria notably increased with higher nitrogen application levels, particularly evident in the IV treatment group where it surpassed the control group. Considering that nitrogen addition first changes soil nutrients and then lowers soil pH, the abundance of certain oligotrophic bacteria like Acidobacteria can be caused, which showed a first decreasing and then increasing trend. On the contrary, eutrophic bacteria, such as Actinobacteria and Proteobacteria, displayed a decline. From the redundancy analysis, it was highlighted that total nitrogen and pH were the primary driving forces affecting the bacterial community composition.

Osteoarthritis (OA) is a degenerative disease potentially exacerbated due to inflammation, cartilage degeneration, and increased friction. Both mesenchymal stem cells (MSCs) and pro-inflammatory macrophages play important roles in OA. A promising approach to treating OA is to modify multi-functional hydrogel microspheres to target the OA microenvironment and structure. Arginyl-glycyl-aspartic acid (RGD) is a peptide widely used in bioengineering owing to its cell adhesion properties, which can recruit BMSCs and macrophages. We developed TLC-R, a microsphere loaded with TGF-β1-containing liposomes. The recruitment effect of TLC-R on macrophages and BMSCs was verified by in vitro experiments, along with its function of promoting chondrogenic differentiation of BMSCs. And we evaluated the effect of TLC-R in balancing OA metabolism in vitro and in vivo. When TLC-R was co-cultured with BMSCs and lipopolysaccharide (LPS)-treated macrophages, it showed the ability to recruit both cells in substantial numbers. As the microspheres degraded, TGF-β1 and chondroitin sulfate (ChS) were released to promote chondrogenic differentiation of the recruited BMSCs, modulate chondrocyte metabolism and inhibit inflammation induced by the macrophages. Furthermore, in vivo analysis showed that TLC-R restored the narrowed space, reduced osteophyte volume, and improved cartilage metabolic homeostasis in OA rats. Altogether, TLC-R provides a comprehensive and novel solution for OA treatment by dual-modulating inflammatory and chondrocyte metabolism.

In order to explore the land ecological environment and landscape changes in the west, this paper builds an intelligent evaluation model based on image classification algorithms and geographic information systems. To address the challenges associated with video Geographic Information System (GIS) data retrieval, this study focuses on the organization model for such data and aims to achieve efficient and comprehensive key frame retrieval in video GIS. The research utilizes global features, local features, and deep features present in video GIS data to enhance the retrieval process and improve the quality and comprehensiveness of the retrieved results. A deep neural network is used to extract relevant features from the video GIS data, and hash coding is applied to encode the high-level features derived from the network. This approach enables efficient retrieval based on the extracted features, contributing to more accurate and relevant search results. The findings indicate that the model developed in this study has demonstrated certain practical benefits and can be effectively applied to video GIS data retrieval tasks.

Abstract Background Androgenetic alopecia (AGA), one of the most common types of hair loss, is associated with oxidative stress, inflammation and aging. Derinat, a transient receptor potential canonical channels (TRPCs) inhibitor, restrains TRPCs-mediated increase intracellular Ca2+ signaling, which initiates the skin aging process with intracellular reactive oxygen species (ROS) accumulation. This study investigated whether Derinat protected skin from oxidative stress-induced damage and aging, thus inhibiting AGA pathogenesis. Methods The lifespan of Caenorhabditis elegans was measured to examine the capacity of Derinat to oppose the oxidative stress induced-aging process, which drives the hair cycle from anagen to catagen phase. The experiments that used BALB/c-nu and C57BL/6 mice determined the effects of Derinat on hair cycle and oxidative stress in skin. To further apply Derinat to clinical study, the resulting relationship between AGA pathogenesis and TRPCs-regulated oxidative stress was confirmed using the bioinformatics approach. We consequently used the parameters of hair density, hair diameter, hair recovery and quality of life index to evaluate the effect of Derinat treatment on AGA subjects. Results Derinat restrained the oxidative stress induced-aging process sufficiently to extend the lifespan of worms. Derinat also changed the hair growth patterns of mice by maintenance of the hair cycle at the anagen phase. This efficacy was due to reduction of TRPCs-mediated ROS accumulation. Because the bioinformatics analysis found that AGA pathogenesis is associated with TRPCs-regulated oxidative stress and inflammation, treatment with Derinat in AGA subjects increased positive outcomes of oral medication while mitigating the impairment of AGA subjects’ quality of life. Conclusions Derinat restrains AGA pathogenesis and may provide a new therapeutic approach for treating AGA. ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022. Trial registration ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022

Chronic viral infections cause T cell dysfunction in both animal models and human clinical settings, thereby affecting the ability of the host immune system to clear viral pathogens and develop proper virus-specific immune memory. However, the impact of chronic viral infections on the host's immune memory to other pathogens has not been well described. In this study, we immunized mice with recombinant Listeria monocytogenes expressing OVA (Lm-OVA) to generate immunity to Lm and allow analysis of OVA-specific memory T (Tm) cells. We then infected these mice with lymphocytic choriomeningitis virus (LCMV) strain Cl-13 which establishes a chronic infection. We found that chronically infected mice were unable to protect against Listeria re-challenge. OVA-specific Tm cells showed a progressive loss in total numbers and in their ability to produce effector cytokines in the context of chronic LCMV infection. Unlike virus-specific T cells, OVA-specific Tm cells from chronically infected mice did not up-regulate the expression of inhibitory receptors, a hallmark feature of exhaustion in virus-specific T cells. Finally, OVA-specific Tm cells failed to mount a robust recall response after bacteria re-challenge both in the chronically infected and adoptively transferred naïve hosts. These results show that previously established bacteria-specific Tm cells become functionally impaired in the setting of an unrelated bystander chronic viral infection, which may contribute to poor immunity against other pathogens in the host with chronic viral infection.

Oxidative stress-induced apoptosis is an important pathological process in renal ischemia/reperfusion injury (RIRI). Theaflavin (TF) is the main active pigment and polyphenol in black tea. It has been widely reported because of its biological activity that can reduce oxidative stress and protect against many diseases. Here, we explored the role of theaflavin in the pathological process of RIRI. In the present study, the RIRI model of 45 min ischemia and 24 h reperfusion was established in C57BL/6 J male mice, and theaflavin was used as an intervention. Compared with the RIRI group, the renal filtration function, renal tissue damage and antioxidant capacity of the theaflavin intervention group were significantly improved, while the level of apoptosis was reduced. TCMK-1 cells were incubated under hypoxia for 48 h and then reoxygenated for 6 h to simulate RIRI in vitro. The application of theaflavin significantly promoted the translocation of p53 from cytoplasm to nucleus, upregulated the expression of glutathione peroxidase 1 (GPx-1) in cells, and inhibited oxidative stress damage and apoptosis. Transfection with p53 siRNA can partially inhibit the effect of theaflavin. Thus, theaflavin exerted a protective effect against RIRI by inhibiting apoptosis and oxidative stress via regulating the p53/GPx-1 pathway. We conclude that theaflavin has the potential to become a candidate drug for the prevention and treatment of RIRI.

Two phytoplankton blooms triggered by the tropical cyclone (TC) Hibaru were studied in the Bay of Bengal. Hibaru occurred in southeastern Sri Lanka in January 2005. After the passage of Hibaru, two strong phytoplankton blooms appeared in the study area (3.5° N-6° N, 83.5° E-88.5° E). In this study, the dynamic mechanisms were investigated with remote sensing, multisource reanalysis products and Argo float data. The first bloom on January 19 to 20 was induced by upwelling with the upper cyclonic eddy and mixed entrainment caused by Hibaru, where the maximum chlorophyll a (Chl-a) concentration was 0.235 mg•m–3. Sea surface cooling and heavy rainfall also occurred. The second bloom from January 27 to 28 was triggered by the interaction of the upper cyclonic eddy and submarine anticyclonic eddy after the passage of Hibaru, where the maximum of the Chl-a concentration was 0.124 mg•m–3. With the submarine anticyclonic eddy and weakened barrier layer thickness (BLT), the subsurface horizontally converged chlorophyll and nutrient water was uplifted with upwelling. This study contributes to the assessment of the ecological impact of ocean eddies during the passage of TC in the Bay of Bengal.

Extrapolation of implosion performance between different laser energy scales is investigated for indirect drive through a semi-hydro-equivalent design. Since radiation transport is non-hydro-equivalent, the peak radiation temperature of the hohlraum and the ablation velocity of the capsule ablator are not scale-invariant when the sizes of the hohlraum and the capsule are scale-varied. A semi-hydro-equivalent design method that keeps the implosion velocity Vi, adiabat αF, and PL/Rhc2 (where PL is the laser power and Rhc is the hohlraum and capsule scale length) scale-invariant, is proposed to create hydrodynamically similar implosions. The semi-hydro-equivalent design and the scaled implosion performance are investigated for the 100 kJ Laser Facility (100 kJ-scale) and the National Ignition Facility (NIF-scale) with about 2 MJ laser energy. It is found that the one-dimensional implosion performance is approximately hydro-equivalent when Vi and αF are kept the same. Owing to the non-hydro-equivalent radiation transport, the yield-over-clean without α-particle heating (YOCnoα) is slightly lower at 100 kJ-scale than at NIF-scale for the same scaled radiation asymmetry or the same initial perturbation of the hydrodynamic instability. The overall scaled two-dimensional implosion performance is slightly lower at 100 kJ-scale. The general Lawson criterion factor scales as χnoα2D∼S1.06±0.04 (where S is the scale-variation factor) for the semi-hydro-equivalent implosion design with a moderate YOCnoα. Our study indicates that χnoα ≈ 0.379 is the minimum requirement for the 100 kJ-scale implosion to demonstrate the ability to achieve marginal ignition at NIF-scale.

Cuproptosis, a distinct form of programmed cell death, is an emerging field in oncology with promising implications. This novel mode of cell death has the potential to become a regulatory target for tumor therapy, thus expanding the currently limited treatment options available for patients with cancer. Our research team focused on investigating the role of functional long non-coding RNA (lncRNAs) in hepatocellular carcinoma (HCC). We were particularly intrigued by the potential implications of HCC-lncRNAs on cuproptosis. Through a comprehensive analysis, we identified three cuproptosis-related lncRNAs (CRLs): AC018690.1, AL050341.2, and LINC02038. These lncRNAs were found to influence the sensitivity of HCC to cuproptosis. Based on our results, we constructed a risk model represented by the equation: risk score = 0.82 * AC018690.1 + 0.65 * AL050341.2 + 0.61 * LINC02038. Notably, significant disparities were observed in clinical features, such as the response rate to immunotherapy and targeted therapy, as well as in cellular characteristics, including the composition of the tumor immune microenvironment (TIME), when comparing the high- and low-risk groups. Most importantly, knockdown of these CRLs was confirmed to significantly weaken the resistance to cuproptosis in HCC. This effect resulted from the accelerated accumulation of lipoacylated-DLAT and lipoacylated-DLST. In summary, we identified three CRLs in HCC and established a novel risk model with potential clinical applications. Additionally, we proposed a potential therapeutic method consisting of sorafenib-copper ionophores-immunotherapy.

ObjectiveThis study aimed to investigate the relationship between intraoperative hip arthrogram parameters and residual acetabular dysplasia (RAD) and avascular necrosis of the femoral head (AVN) in children with developmental dysplasia of the hip (DDH) treated by closed reduction.MethodsWe retrospectively analyzed the data of 102 patients (110 hips; mean age, 14.6 months ± 4.7 months) with DDH treated by closed reduction. A hip arthrogram was routinely performed during the operation. The femoral head coverage rate (FHC), medial pool distance of the hip (MPD), labral inversion, and reduction quality classification were evaluated under the hip arthrogram. The presence of RAD and AVN was assessed on radiographs at the last follow-up. The relationship between each arthrogram parameter and RAD as well as AVN was investigated using a t-test, chi-square test, and logistic regression.ResultsThe overall FHC and medial pool distance of the hip (MDP) averaged 42.2% ± 12% and 8.1% ± 11.7%, respectively. There were 80 hips (72.7%) with labral inversion and 30 hips (27.2%) without. The reduction quality was type A in 57 hips (51.8%), type B in 28 hips (25.4%), and type C in 25 hips (22.7%). A total of 32 hips (29%) were in the RAD group, and 78 hips (71%) were in the recovered group according to whether pelvic osteotomy was performed or not and according to the last Severin grade. The FHC was significantly higher in the recovered group than that in the RAD group (P = 0.014). No significant difference was observed in sex, age at reduction, side, preoperative acetabular index, International Hip Dysplasia Institute classification, follow-up time, quality of reduction, MDP, and proportion of labral inversion between the recovered and RAD groups. Logistic regression analysis showed that only the FHC was a risk factor for RAD. The incidence of AVN above type II was 11.8% in this group of patients, and the incidence of AVN was significantly higher in patients with labral inversion (23.2%) than that in those without (7.5%; P = 0.041). Logistic regression analysis showed that labral inversion was a risk factor for AVN.ConclusionThe FHC measured under arthrogram can predict the occurrence of RAD after closed reduction of DDH, whereas MDP, reduction quality classification, and labral inversion are of little significance. Labral inversion is a risk factor for AVN.

BackgroundSkilled birth attendants (SBA) facilitate identifying and overcoming labor problems and saving lives. With one of the highest maternal death rates in the Asia-Pacific area, SBA utilization during childbirth among Papua New Guinea (PNG) women remains low. Women’s status and empowerment are important factors in maternal and child health services and critical to maternal and child health development. This study is intended to apply structural equation modeling based on data from the Demographic and Health Survey (DHS) to evaluate the causal relationship between women’s status, empowerment, and SBA utilization in PNG and the mechanisms of their influence.MethodsThis study employed data from the 2016–2018 Papua New Guinea Demographic Health Survey (PNG DHS), which recruited 18,175 women aged 15–49 years. A multi-stage sample and a structured questionnaire were used to collect information on maternal health, women’s empowerment, and related topics. STATA 17.0 was used to describe the data, while MPLUS 8.2 was employed for structural equation modeling and pathway analysis.ResultsThe two empowerment dimensions of household decision-making (standardized path coefficient, β = 0.049, p

Abstract Background This study assessed the distribution characteristics of pathogens isolated from cases of orthopedic infections and focused on the antimicrobial susceptibility of the main pathogens. Methods This retrospective study involved patients with orthopedic infection in a tertiary medical center located in Shanghai, China, from 2008 to 2021.Pathogen information and the basic information of patients were identified from clinical microbiology laboratory data and the institutional medical record system. Results In total, the pathogen information of 2821 patients were enrolled in the study. S. aureus (37.71%) was the main causative pathogen responsible for orthopedic infection. Gender, pathogens distribution and polymicrobial infection rates were significantly different (P

With the development of Chinese society, there is an increasing demand for emissions reduction and the stable operation of the power grid. Regional comprehensive energy supply systems have entered the public’s view owing to their advantages of reducing capacity, unified dispatch, improving efficiency, and reducing energy consumption. This paper focuses on a system under construction in Chongqing, which adopts a combined gas tri-supply (combined cooling, heat, and power, CCHP) and dynamic ice storage cooling system as the research object. By establishing a mathematical model for the simulation research, this study examines the start–stop priority sequence of the gas tri-supply subsystem and the heat pump subsystem under the ice storage priority strategy in winter and summer and proposes corresponding optimization solutions. By comparing the annual operating energy consumption of the system, we conclude that the gas tri-supply composite system has good economic efficiency and peak-shaving capability, indicating that regional gas tri-supply composite systems have great application potential in the future. The proposed optimized operation strategy and simulated energy consumption calculation provide theoretical guidance for the construction and operation of both this project and similar projects.

Complex construction projects are characterized by a large scale, high dynamics, many unknown risks, high complexity, etc., which often result in serious consequences, such as schedule delays, cost overruns, and uncontrolled objectives. Organizational leadership, which can be dynamically adjusted to the changes in the external environment, is the most important management ability of project managers. Therefore, it is of great significance to systematically analyze organizational leadership for the management of complex construction projects. In this paper, through the dynamic Bayesian method, the influencing factors of organizational leadership of complex construction projects and its dynamic development law are studied in depth. First, 17 organizational leadership factors are identified. Second, a dynamic Bayesian measurement model of organizational leadership was developed using 128 training samples. Third, the developed measurement model was applied for model analysis. The results of the study are as follows. (1) This study models changes in organizational leadership influences over time. (2) The organizational leadership measurement model proposed in this study can be applied in practice to predict leadership trends in specific projects. (3) Leaders should pay more attention to management competence in the personal leadership dimension, culture building in the relational leadership dimension, and institutional support in the strategic leadership dimension. This study proposes a quantifiable model for project leaders that breaks through the traditional model of studying organizational leadership from a static perspective, provides a quantifiable model for project leaders, and can cope with the dynamics of actual projects so that project leaders can control the whole leadership process macroscopically, thus providing an important reference to improve the organizational leadership capacity of complex construction projects.

Abstract Quorum cheating, a socio-microbiological process that is based on mutations in cell density-sensing (quorum-sensing) systems, has emerged as an important contributor to biofilm-associated infection in the leading human pathogen Staphylococcus aureus. This is because inactivation of the staphylococcal Agr quorum-sensing system leads to pronounced biofilm formation, increasing resistance to antibiotics and immune defense mechanisms. Since biofilm infections in the clinic usually progress under antibiotic treatment, we here investigated whether such treatment promotes biofilm infection via the promotion of quorum cheating. Quorum cheater development was stimulated by several antibiotics used in the treatment of staphylococcal biofilm infections more strongly in biofilm than in the planktonic mode of growth. Sub-inhibitory concentrations of levofloxacin and vancomycin were investigated for their impact on biofilm-associated (subcutaneous catheter-associated and prosthetic joint-associated infection), where in contrast to a non-biofilm-associated subcutaneous skin infection model, a significant increase of the bacterial load and development of agr mutants was observed. Our results directly demonstrate the development of Agr dysfunctionality in animal biofilm-associated infection models and reveal that inappropriate antibiotic treatment can be counterproductive for such infections as it promotes quorum cheating and the associated development of biofilms.

Abstract Background The study objective was to validate the relative biological effectiveness (RBE) calculated by the modified microdosimetric kinetic model in RayStation (Ray-MKM) for active-energy scanning carbon-ion radiotherapy. Methods The Ray-MKM was benchmarked using a spread-out Bragg-peak (SOBP) plan, which was suggested in literature from the National Institute of Radiobiological Science (NIRS) in Japan. The residual RBE differences from the MKM at NIRS (NIRS-MKM) were derived using several SOBP plans with different ranges, SOBP widths, and prescriptions. To investigate the origins of the differences, we compared the saturation-corrected dose-mean specific energy $$Z_{1D}^{*}$$ Z 1 D ∗ of the aforementioned SOBPs. Furthermore, we converted the RBE-weighted doses with the Ray-MKM to those with local effect model I (LEM doses). The purpose was to investigate whether the Ray-MKM could reproduce the RBE-weighted conversion study. Results The benchmark determined the value of the clinical dose scaling factor, $$F_{clin}$$ F clin , as 2.40. The target mean RBE deviations between the Ray-MKM and NIRS-MKM were median: 0.6 (minimum: 0.0 to maximum: 1.69) %. The $$Z_{1D}^{*}$$ Z 1 D ∗ difference in-depth led to the RBE difference in-depth and was remarkable at the distal end. The converted LEM doses from the Ray-MKM doses were comparable (the deviation being − 1.8–0.7%) to existing literature. Conclusion This study validated the Ray-MKM based on our active-energy scanning carbon-ion beam via phantom studies. The Ray-MKM could generate similar RBEs as the NIRS-MKM after benchmarking. Analysis based on $$Z_{1D}^{*}$$ Z 1 D ∗ indicated that the different beam qualities and fragment spectra caused the RBE differences. Since the absolute dose differences at the distal end were small, we neglected them. Furthermore, each centre may determine its centre-specific $$F_{clin}$$ F clin based on this approach.

Abstract Plasmodium falciparum causes the most severe malaria in humans. Immunoglobulin M (IgM) serves as the first line of humoral defense against infection and potently activates the complement pathway to facilitate P. falciparum clearance. A number of P. falciparum proteins bind IgM, leading to immune evasion and severe disease. However, the underlying molecular mechanisms remain unknown. Here, using high-resolution cryo-electron microscopy, we delineate how P. falciparum proteins VAR2CSA, TM284VAR1, DBLMSP, and DBLMSP2 target IgM. Each protein binds IgM in a different manner, and together they present a variety of Duffy-binding-like domain-IgM interaction modes. We further show that these proteins interfere directly with IgM-mediated complement activation in vitro, with VAR2CSA exhibiting the most potent inhibitory effect. These results underscore the importance of IgM for human adaptation of P. falciparum and provide critical insights into its immune evasion mechanism.

Abstract Current biotechnologies can simultaneously measure multiple high-dimensional modalities (e.g., RNA, DNA accessibility, and protein) from the same cells. A combination of different analytical tasks (e.g., multi-modal integration and cross-modal analysis) is required to comprehensively understand such data, inferring how gene regulation drives biological diversity and functions. However, current analytical methods are designed to perform a single task, only providing a partial picture of the multi-modal data. Here, we present UnitedNet, an explainable multi-task deep neural network capable of integrating different tasks to analyze single-cell multi-modality data. Applied to various multi-modality datasets (e.g., Patch-seq, multiome ATAC + gene expression, and spatial transcriptomics), UnitedNet demonstrates similar or better accuracy in multi-modal integration and cross-modal prediction compared with state-of-the-art methods. Moreover, by dissecting the trained UnitedNet with the explainable machine learning algorithm, we can directly quantify the relationship between gene expression and other modalities with cell-type specificity. UnitedNet is a comprehensive end-to-end framework that could be broadly applicable to single-cell multi-modality biology. This framework has the potential to facilitate the discovery of cell-type-specific regulation kinetics across transcriptomics and other modalities.

The restoration and reconstruction of mangrove wetland ecosystem is one of the key research fields in ecological restoration in the coastal zone of South China. In order to reveal the physiological and ecological strategies to light conditions of mangrove species, the characteristics of leaf soluble protein contents and activities of antioxidant enzymes in seedlings of eight mangrove species (Sonneratia apetala, Kandelia obovata, Bruguiera gymnorhiza, Aegiceras corniculatum, Acanthus ilicifolius, Acrostichum aureum, Heritiera littoralis and Hibiscus tiliaceus) under different light intensity treatments (100%, 45%, 30%, and 10% of natural light intensity) were studied using shading control experiment. The results were as follows: (1) Low light intensities had little effect on the leaf soluble protein contents of Bruguiera gymnorhiza, Acanthus ilicifolius and Acrostichum aureum, whereas the other five species showed a decreasing trend of leaf soluble protein contents with the decline in light intensity. (2) The activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in the leaves of Bruguiera gymnorhiza, Acanthus ilicifolius and Acrostichum aureum under 10% of natural light intensity treatment had no significant differences compared with the control, while the other five mangrove species showed a decreasing trend of all the five antioxidant enzyme activities. In conclusion, the results indicate that Bruguiera gymnorhiza, Acanthus ilicifolius and Acrostichum aureum are suitable to be planted under the forest with high canopy density, while Sonneratia apetala, Kandelia obovata, Aegiceras corniculatum, Heritiera littoralis, Hibiscus tiliaceus are suitable to be planted under the forest with lower canopy density or planted as middle and upper layer tree species in mangrove. The results of this study provide theoretical guidance for the optimal allocation of artificial mangrove communities.

[Objective] The relationship between vegetation cover changes and extreme climate in Shandong Province was studied in order to provide a reference for regional vegetation ecological maintenance. [Methods] Based on the 1982—2021 long-term NDVI data set obtained from AVHRR-GIMMS NDVI interpolation of MODIS NDVI, the temporal and spatial changes of NDVI in Shandong Province were analyzed, and the daily data of 96 weather stations in the province were combined to study the response of NDVI to extreme climate. [Results] ① NDVI in Shandong Province and its subregions showed an overall strong and sustained upward trend, with an average growth rate of 0.013/10 yr (p

Online automated identification of farmland pests is an important auxiliary means of pest control. In practical applications, the online insect identification system is often unable to locate and identify the target pest accurately due to factors such as small target size, high similarity between species and complex backgrounds. To facilitate the identification of insect larvae, a two-stage segmentation method, MRUNet was proposed in this study. Structurally, MRUNet borrows the practice of object detection before semantic segmentation from Mask R-CNN and then uses an improved lightweight UNet to perform the semantic segmentation. To reliably evaluate the segmentation results of the models, statistical methods were introduced to measure the stability of the performance of the models among samples in addition to the evaluation indicators commonly used for semantic segmentation. The experimental results showed that this two-stage image segmentation strategy is effective in dealing with small targets in complex backgrounds. Compared with existing state-of-the-art semantic segmentation methods, MRUNet shows better stability and detail processing ability under the same conditions. This study provides a reliable reference for the automated identification of insect larvae.

Summary: In biological systems, protein function depends on spatial and temporal changes known as protein dynamics, which can be probed by amide hydrogen/deuterium (H/D) exchange. Here, we present a protocol for determining protein dynamics by Fourier-transform infrared (FT-IR) spectroscopy. We describe steps for protein sample preparation and FT-IR spectra collection. We then detail procedures for spectra analysis. Applications include the effects of protein mutation or protein and metal ion or ligand interactions on the protein H/D exchange rate.For complete details on the use and execution of this protocol, please refer to Yu et al. (2013).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

ABSTRACTThe virulence factors of Staphylococcus aureus are tightly controlled by two-component systems (TCSs) and small RNA (sRNA). TCSs have been well studied over the past several decades, but our understanding of sRNA functions lags far behind that of TCS functions. Here, we studied the biological role of sRNA from 506 S. aureus RNA-seq datasets using independent component analysis (ICA). We found that a previously neglected sRNA, Sau-41, functions in the Agr system. Sau-41 is located within the PSMα operon and controlled by the Agr system. It was predicted to share 22-base complementarity with RNAIII, a major regulator of S. aureus virulence. The EMSA results demonstrated that Sau-41 directly binds to RNAIII. Furthermore, our results found that Sau-41 is capable of repressing S. aureus haemolysin activity by downregulating α-haemolysin and δ-toxin. The repression of α-haemolysin was attributed to the competition between the 5’ UTR of hla and Sau-41 for binding RNAIII. We observed that Sau-41 mitigated S. aureus virulence in an orthopaedic implant infection mouse model and alleviated osteolysis. Together, our results indicate that Sau-41 is a virulence-regulating RNA and suggest that Sau-41 might be involved in a negative feedback mechanism to control the Agr system. This work is a demonstration of using ICA in sRNA identification by mining high-throughput data and could be extended to other organisms as well.

Earthquakes are environmental disturbances affecting ecosystem functioning, health, and biodiversity, but their potential impacts on plant–soil interface are still poorly understood. In this study, grassland habitats in areas near and away from the seismo-fault in Madou, a region typical of alpine conditions on the Qinghai–Tibetan Plateau, were randomly selected. The impacts of earthquake on soil properties and plant nutrient content in the short term were emphasized, and their potential relationships with community diversity and productivity were examined. According to the findings of the study, the Maduo earthquake led to a decrease in soil nutrient content in alpine grassland ecosystems, especially soil TC, TN, TP, TCa, AP, AK, NH4+-N, and SOC, and inhibited the absorption of N, Ca, and Mg nutrients by plants. In addition, the diversity and productivity of communities were affected by both direct and indirect earthquake pathways. The negative impacts of seismic fracture on soil structure had the most significant direct impact on plant community diversity. Earthquakes also indirectly reduced community productivity by reducing the soil N content and inhibiting the absorption of plant nutrients. Our findings suggested that earthquakes could potentially decrease the stability of the alpine grassland ecosystem on the QTP by affecting nutrient availability at the plant–soil interface.

Abstract Cellulose is the most abundant and “green” biomass resource on earth and gains tremendous attention. It is expected to become an alternative for traditional chemical and petroleum resources. This review describes the traditional solvents used for industrial processes, the non‐derivative organic solvents, and the aqueous solution systems, along with their dissolution mechanisms and development of fiber‐spinning processes. The problems associated with the industrial production of viscose fibers and cuprammonium fibers are also discussed. This paper focuses on the research status of regenerated cellulose fibers (RCFs) prepared with green and no‐pollution aqueous solutions and provides some effective strategies and methods for improving the mechanical strength of RCFs and promoting the implementation of industrial production. Lastly, the current developments of RCFs are summarized and prospected and it would serve as a guide for the developmental trend and research direction of RCFs in the future.

Abstract Background This study aimed to delineate the cell heterogeneity in the bone-implant interface and investigate the fibroblast responses to implant-associated S. aureus infection. Methods Single-cell RNA sequencing of human periprosthetic tissues from patients with periprosthetic joint infection (PJI, n = 3) and patients with aseptic loosening (AL, n = 2) was performed. Cell type identities and gene expression profiles were analyzed to depict the single-cell landscape in the periprosthetic environment. In addition, 11 publicly available human scRNA-seq datasets were downloaded from GSE datasets and integrated with the in-house sequencing data to identify disease-specific fibroblast subtypes. Furthermore, fibroblast pseudotime trajectory analysis and Single-cell regulatory network inference and clustering (SCENIC) analysis were combined to identify transcription regulators responsible for fibroblast differentiation. Immunofluorescence was performed on the sequenced samples to validate the protein expression of the differentially expressed transcription regulators. Results Eight major cell types were identified in the human bone-implant interface by analyzing 36,466 cells. Meta-analysis of fibroblasts scRNA-seq data found fibroblasts in the bone-implant interface express a high level of CTHRC1. We also found fibroblasts could differentiate into pro-inflammatory and matrix-producing phenotypes, each primarily presented in the PJI and AL groups, respectively. Furthermore, NPAS2 and TFEC which are activated in PJI samples were suggested to induce pro-inflammatory polarization in fibroblasts, whereas HMX1, SOX5, SOX9, ZIC1, ETS2, and FOXO1 are matrix-producing regulators. Meanwhile, we conducted a CMap analysis and identified forskolin as a potential regulator for fibroblast differentiation toward matrix-producing phenotypes. Conclusions In this study, we discovered the existence of CTHRC1 + fibroblast in the bone-implant interface. Moreover, we revealed a bipolar mode of fibroblast differentiation and put forward the hypothesis that infection could modulate fibroblast toward a pro-inflammatory phenotype through NPAS2 and TFEC.

Abstract Background Hepatitis B virus (HBV) reactivation impact negatively the prognosis of patients with HBV-related hepatocellular carcinoma (HCC). This study aimed to observe the effect of antiviral therapy (AVT) on viral reactivation and long-term outcomes after percutaneous radiofrequency ablation (PRFA) for HBV-related HCC. Methods Data on 538 patients between 2009 and 2013 were reviewed. Propensity score matching (PSM) analysis was used to adjust for differences in baseline features between patients who received AVT (AVT group) and did not receive it (non-AVT group). Logistic regression was used to identify the independent factors for viral reactivation. The tumor recurrence and overall survival (OS) rates were analyzed using the Kaplan–Meier method. Recurrence patterns were also investigated. Results HBV reactivation developed in 10.8% (58/538) of patients after PRFA. AVT was associated independently with decreased viral reactivation (odd ratio: 0.061, 95% confidence interval: 0.018–0.200). In 215 pairs of patients obtained after PSM, the AVT group had lower 1-, 3-, and 5-year recurrence rates (24%, 55%, and 67% vs 33%, 75%, and 85%, respectively) and higher 1-, 3-, and 5-year OS rates (100%, 67%, and 59% vs 100%, 52%, and 42%, respectively) than non-AVT group (P

Efficient trajectory and path planning (TPP) is essential for unmanned aircraft systems (UASs) autonomy in challenging environments. Despite the scale ambiguity inherent in monocular vision, characteristics like compact size make a monocular camera ideal for micro-aerial vehicle (MAV)-based UASs. This work introduces a real-time MAV system using monocular depth estimation (MDE) with novel scale recovery module for autonomous navigation. We present MoNA Bench, a benchmark for Monocular depth estimation in Navigation of the Autonomous unmanned Aircraft system (MoNA), emphasizing its obstacle avoidance and safe target tracking capabilities. We highlight key attributes—estimation efficiency, depth map accuracy, and scale consistency—for efficient TPP through MDE.

The YxNi2−yMny system was investigated in the region 0.825 ≤ x ≤ 0.95, 0.1 ≤ y ≤ 0.3. The alloys were synthesized by induction melting and corresponding annealing. The substitution of Mn for Ni (y = 0.1) favors the formation of a C15 structure with disordered Y vacancies against the superstructure of Y0.95Ni2. For y = 0.2 and 0.3, Mn can substitute in both Y and Ni sites. Single-phase compounds with a C15 structure can be formed by adjusting both the Y and Mn contents. Their hydrogen absorption–desorption properties were measured by pressure–composition isotherm (PCI) measurements at 150 °C, and the hydrides were characterized at room temperature by X-ray diffraction and TG–DSC experiments. The PCIs show two plateaus corresponding to the formation of crystalline and amorphous hydrides. The heating of the amorphous hydrides leads to an endothermic desorption at first and then a recrystallization into Y(Ni, Mn)3 and YHx phases. At higher temperatures, the Y hydride desorbs, and a recombination into a Y(Ni, Mn)2 Laves phase compound is observed. For y = 0.1, vacancy formation in the Y site and partial Mn substitution in the Ni site enhance the structural stability and suppress the hydrogen-induced amorphization (HIA). However, for a larger Mn content (y ≥ 0.2), Mn substitutes also in the Y sites at the expense of Y vacancies. This yields worse structural stability upon hydrogenation than for y = 0.1, as the mean ratio r(Y, Mn)/r(Ni/Mn) becomes larger than for y = 0.1 r(Y, ☐)/r(Ni/Mn).

The root residual stress during gear machining has a significant impact on the bending fatigue performance of the gear. The process parameters of gear hobbing (hob speed, axial feed speed, and radial cutting depth) directly affect the residual stress of the tooth root. To investigate the relationship between the process parameters of hobbing and the residual stress of the tooth root respectively, an analysis of an orthogonal and single factor was conducted in the hobbing experiment, taking into account the interactions among factors, which revealed the influence rule and primary–secondary relationship of the process parameters on the residual stress of the tooth root. The importance coefficients of the process parameters on the residual stress of the tooth root were calculated using the Least Absolute Shrinkage and Selection Operator (LASSO) method. The results indicate that the residual tensile stress at the tooth root increases with an increase in the hob speed and axial feed speed within the selected range but decreases with an increase in the radial cutting depth. The influence of the process parameters on the residual stress of the tooth root can be ranked as follows: hob speed (importance coefficient 0.460), axial feed speed (importance coefficient 0.278), and radial cutting depth (importance coefficient 0.262). This research provides a basis for improving the residual stress of the tooth root and enhancing the anti-fatigue manufacturing of gears, thus holding significant research value.

A phytoplankton bloom during the passage of Tropical Storm (TS) Chedza was observed at the southern tip of Madagascar on January 28, 2015. The mechanisms of the chlorophyll bloom were researched with satellite remote sensing data, reanalysis data and Argo buoy data. The results show that there was horizontal transport of chlorophyll-a (Chl-a) with the western coastal current of Madagascar and the South East Madagascar Current (SEMC). At the southern tip of Madagascar, there was a tilted anticyclonic eddy moving westward, which promoted the flow of nitrate at depths from 60 m to 100 m northward into Box A for a month. Simultaneously, the SEMC formed another anticyclonic eddy entering Box C. Following the passage of TS Chedza, cyclone vorticity in Box A increased continuously, and the upwelling became stronger with Ekman pumping. At the same time, the barrier layer weakened, the mixed layer deepened, and the thermocline decreased, which can uplift the nitrate to the upper ocean. After the passage of TS Chedza, sufficient photosynthetically active radiation (PAR) facilitated the Chl-a bloom in Box A. This study contributes to the assessment of the ecological impact of ocean eddies at the southern tip of Madagascar.

ABSTRACT Streptococcus pneumoniae (Sp) frequently causes secondary pneumonia after influenza A virus (IAV) infection, leading to high morbidity and mortality worldwide. Concomitant pneumococcal and influenza vaccination improves protection against coinfection but does not always yield complete protection. Impaired innate and adaptive immune responses have been associated with attenuated bacterial clearance in influenza virus-infected hosts. In this study, we showed that preceding low-dose IAV infection caused persistent Sp infection and suppression of bacteria-specific T-helper type 17 (Th17) responses in mice. Prior Sp infection protected against subsequent IAV/Sp coinfection by improving bacterial clearance and rescuing bacteria-specific Th17 responses in the lungs. Furthermore, blockade of IL-17A by anti-IL-17A antibodies abrogated the protective effect of Sp preinfection. Importantly, memory Th17 responses induced by Sp preinfection overcame viral-driven Th17 inhibition and provided cross-protection against different Sp serotypes following coinfection with IAV. These results indicate that bacteria-specific Th17 memory cells play a key role in providing protection against IAV/Sp coinfection in a serotype-independent manner and suggest that a Th17-based vaccine would have excellent potential to mitigate disease caused by coinfection. IMPORTANCE Streptococcus pneumoniae (Sp) frequently causes secondary bacterial pneumonia after influenza A virus (IAV) infection, leading to increased morbidity and mortality worldwide. Current pneumococcal vaccines induce highly strain-specific antibody responses and provide limited protection against IAV/Sp coinfection. Th17 responses are broadly protective against Sp single infection, but whether the Th17 response, which is dramatically impaired by IAV infection in naïve mice, might be effective in immunization-induced protection against pneumonia caused by coinfection is not known. In this study, we have revealed that Sp-specific memory Th17 cells rescue IAV-driven inhibition and provide cross-protection against subsequent lethal coinfection with IAV and different Sp serotypes. These results indicate that a Th17-based vaccine would have excellent potential to mitigate disease caused by IAV/Sp coinfection.

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a clinical threat with high morbidity and mortality. Here, we describe a new simple, rapid identification method for MRSA using oxacillin sodium salt, a cell wall synthesis inhibitor, combined with Gram staining and machine vision (MV) analysis. Gram staining classifies bacteria as positive (purple) or negative (pink) according to the cell wall structure and chemical composition. In the presence of oxacillin, the integrity of the cell wall for methicillin-susceptible S. aureus (MSSA) was destroyed immediately and appeared Gram negative. In contrast, MRSA was relatively stable and appeared Gram positive. This color change can be detected by MV. The feasibility of this method was demonstrated in 150 images of the staining results for 50 clinical S. aureus strains. Based on effective feature extraction and machine learning, the accuracies of the linear linear discriminant analysis (LDA) model and nonlinear artificial neural network (ANN) model for MRSA identification were 96.7% and 97.3%, respectively. Combined with MV analysis, this simple strategy improved the detection efficiency and significantly shortened the time needed to detect antibiotic resistance. The whole process can be completed within 1 h. Unlike the traditional antibiotic susceptibility test, overnight incubation is avoided. This new strategy could be used for other bacteria and represents a new rapid method for detection of clinical antibiotic resistance. IMPORTANCE Oxacillin sodium salt destroys the integrity of the cell wall of MSSA immediately, appearing Gram negative, whereas MRSA is relatively stable and still appears Gram positive. This color change can be detected by microscopic examination and MV analysis. This new strategy has significantly reduced the time to detect resistance. The results show that using oxacillin sodium salt combined with Gram staining and MV analysis is a new, simple and rapid method for identification of MRSA.

Abstract Background The study objective was to validate the relative biological effectiveness (RBE) in RayStation for carbon-ion radiotherapy (CIRT) using the Syngo treatment planning system as reference. Methods Local effect model I was established in RayStation (Ray-LEM) with the same parameters as in LEM I in Syngo (Syngo-LEM). Three cube plans covering most of the tumors treated at our center were generated with Syngo-LEM. Ray-LEM re-calculated the Syngo plans and compared the RBEs to the Syngo counterparts. The results showed that RayStation RBE was smaller than Syngo RBE. To ensure that Ray-LEM reproduced Syngo RBE, the observed deviations were used to scale the maximum RBE (RBEmax) in Ray-LEM. After this calibration, we further compared the RayStation RBE to Syngo RBE using additional plans in both homogeneous phantoms and patients, to ensure that the calibrated Ray-LEM reproduced Syngo RBE even with more complex planning features. Results The calibration increased the RBEmax by 2.3% to raise the Ray-LEM RBE. The target mean RBE deviations in the phantom evaluation plans were median: 0.0 (minimum: − 1.1 to maximum: 0.7) %, and the target mean RBE deviations of the clinical target volumes of 16 patient cases were − 0.4 (− 1.5 to 0.2) %. Conclusions The residual RBE difference between RayStation and Syngo was found to be ≤ 1.0%. Thus, we can propose to use RayStation for clinical CIRT treatment planning. However, the potential differences due to the absorbed beam model warrants further exploration.

Abstract Objective A micromotion-based balanced drilling system was designed based on a locking plate (LP) and far cortical locking (FCL) concept to maintain the balance of micromotions of the cortex on both sides of a fracture region. The system was tested by axial compression test. Methods The fracture gap was set to 2 cm, and locking screws with a diameter of 5 mm and a locking plate were used to fix it. The diameters of the two sections of the stepping drill were 3.5 mm and 5.0 mm, respectively. One of the matching drilling sleeves was a standard sleeve (eccentricity, 0 mm) and the other was an eccentric sleeve (proximal eccentricity, 1 mm). A model of the fixed locking plate (AO/ASIF 33-A3) for distal femoral fractures with a gap of 2 cm was established based on data from 42 artificial femurs (SAWBONE). According to the shape of the screw holes on the cortex, the fixed fracture models were divided into a control group (standard screw hole group X126, six cases) and an experimental group (elliptical screw hole group N, 36 cases). The experimental group was further divided into six subgroups with six cases in each (N126, N136, N1256, N1356, N12356, N123456), based on the number and distribution of the screws on the proximal fracture segment. The control, N126, and N136 groups were subjected to an axial load of 500 N, and the other groups were subjected to an axial load of 1000 N. The displacements of the kinetic head, far cortex, and near cortex were measured. The integral structural stiffness of the model and the near cortical strain were calculated. The data of each group were analyzed by using a paired t-test. Results When the far cortical strains were 2%, 5%, and 10%, the near cortical strains in group N126 were 0.96%, 2.35%, and 4.62%, respectively, significantly higher than those in the control group (X126) (p 0.05). For different numbers of screws, the near cortical strains in the three-screw groups were significantly higher than those in the four-screw groups (p 0.05). Conclusion The proposed drill and matching sleeves enabled a conventional locking compression plate to be transformed into an internal fixation system to improve the balanced motion of the near and far cortices. Thus, strain on a fracture site could be controlled by adjusting the diameter of the drill and the eccentricity of the sleeve.

Abstract Background Nonalcoholic steatohepatitis (NASH) occupies a substantial proportion of chronic liver disease worldwide, of which pathogenesis needs further research. Recent studies have demonstrated the significant roles of circular RNAs (circRNAs) in NASH, while the function of a novel type of circRNAs, namely mitochondria-encoded circRNAs (mecciRNAs), remains elusive. Therefore, we aimed to investigate their potential to regulate the progression of NASH in this study. Methods GSE134146 was used to screen for differentially expressed mecciRNAs in NASH, while GSE46300 was used to identify NASH-related genes. To establish the mecciRNA-miRNA-mRNA networks, circMINE and miRNet databases were used for predicting downstream targets. Then, consensus clustering analysis was used to determine immune subtypes of NASH. Finally, we successfully validated our findings in vitro (LPS-treated hepatic stellate cells [HSCs]) and in vivo (MCD-diet mice) NASH models. Results We confirmed that circRNomics balance is disrupted in HSCs of NASH, while two mecciRNAs (hsa_circ_0089761 and hsa_circ_0089763) could function as competing for endogenous RNAs (ceRNAs) to regulate fibrosis-related signals. Furthermore, we constructed two ceRNA networks based on mecciRNAs for the first time. Cell and animal NASH models validated our findings that c-MYC and SMAD2/3 were upregulated in HSCs, while THBS1 and p-STAT3 were upregulated in hepatocytes. Moreover, we identified 21 core genes by overlapping the differentially expressed genes (NASH vs. Normal) with mecciRNA-targeted genes. According to their expression profiles, NASH patients could be divided in 2 different clusters, in which proinflammatory signals (TNF and IL-17 pathways) are significantly activated in Cluster 1. Conclusion We successfully established two novel mecciRNA-miRNA-mRNA networks in HSCs and hepatocytes, which were further confirmed by in vitro and in vivo models. Meanwhile, the novel immunotyping model revealed the heterogeneity of NASH, thereby might guiding treatment options. Altogether, our study brought a distinct perspective on the relationship between mecciRNAs and NASH.

Bacterial biofilm formation is a major risk of surgical implantation, and necessitates implant removal and aggressive antibiotic treatment. Here authors show that post-surgical application of Manganese-containing inorganic nanosheets reduces residual and recurrent infection by improving antigen presentation and humoral immune response against the biofilms.

Abstract Background N (nitrogen) and P (phosphorus) play important roles in plant growth and fitness, and both are the most important limiting factors that affect grassland structure and function. However, we still know little about plant physiological responses to N and P enrichment in alpine grassland of the Qinghai-Tibetan Plateau. In our experiment, five dominant common herbaceous species were selected and their photosynthetic parameters, leaf N content, and aboveground biomass were measured. Results We found that species-specific responses to N and P enrichment were obvious at individual level. N addition (72 kg Nha−1 yr−1), P addition (36 kg Pha−1 yr−1) and NP addition (72 kg Nha−1 yr−1and 36 kg P ha−1 yr−1, simultaneously) significantly promoted net photosynthetic rate of Leymus secalinus. Differential responses also existed in the same functional groups. Responses of forb species to the nutrients addition varied, Aconitum carmichaeli was more sensitive to nutrients addition including N addition (72 kg Nha−1 yr−1), P addition (36 kg Pha−1 yr−1) and NP addition (72 kg Nha−1 yr−1and 36 kg P ha−1 yr−1). Responses of plant community photosynthetic traits were not so sensitive as those of plant individuals under N and P enrichment. Conclusions Our findings highlighted that photosynthetic responses of alpine plants to N and P enrichment were species-specific. Grass species Leymus secalinus had a higher competitive advantage compared with other species under nutrient enrichment. Additionally, soil pH variation and nutrients imbalance induced by N and P enrichment is the main cause that affect photosynthetic traits of plant in alpine steppe of the Qinghai-Tibetan Plateau.