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Abstract Background Acinetobacter baumannii (AB) is a notable cause of hospital-acquired infections, with carbapenem-resistant Acinetobacter baumannii (CRAB) classified as a high-priority critical pathogen. Bacteriophage therapy is emerging as a promising alternative to combat drug-resistant bacterial infections. In this study, a lytic phage, HZY2308, was isolated from hospital sewage, and the biological properties, biosafety and anti-biofilm properties of phage HZY2308 were characterized and identified. Moreover, the antibacterial effect of phage HZY2308 in combination with antibiotics was investigated, and the apparent characteristics of phage-resistant strain AB48-R were demonstrated, which provided data support for further studies to elucidate the mechanism of generating phage resistance. Methods Phage HZY2308 was isolated by double agar plate method using clinical strain AB48 as the host bacterium. The morphology of phage HZY2308 was identified by transmission electron microscopy (TEM), and biological characteristics of phage HZY2308 were identified by host range, the efficiency of plating (EOP), sensitivity to temperature, pH, and chloroform, one-step growth curve, the optimal multiplicity of infection (MOI), and detection of endotoxin and cytotoxicity. Besides, the complete genome map of HZY2308 was constructed using CGview, and the phylogenetic tree of HZY2308 was constructed with MEGA. Additionally, the full genomic sequence of phage HZY2308 and the selected phage were compared using Easyfig. Checkerboard test of phage HZY2308 in combination with tigecycline (TGC) was performed to investigate their synergistic effect and bactericidal kinetics. The effect of HZY2308 on biofilm was investigated by semi-quantitative staining of biofilm with crystal violet, determination of bacterial activity in biofilm by 2,3-Bis (2-methoxy-4-nitro-5-sulfophenyl) -2 H-tetrazolium-5-carboxanilide (XTT) assay and observation of biofilm structure by fluorescence microscopy. Finally, Phage-resistant bacteria AB48-R were characterized by colony-forming capacity, morphology, growth curves, adsorption efficiency, and antibiotic susceptibility assays. Results A lytic phage, HZY2308, was isolated from hospital sewage, which exhibited advantageous traits such as a brief incubation period, large burst size, and robust stability. Safety assessments conducted at both genetic and cellular levels also have yielded positive outcomes. Besides, phage HZY2308 effectively inhibited AB biofilm formation and disrupted established biofilm structures. Furthermore, a synergistic antibacterial effect was noted when phage HZY2308 was combined with tigecycline. Interestingly, the phage-resistant strain, AB48-R was screened through natural selection. Compared to the wild strain AB48, the adsorption efficiency of the phage to AB48-R diminished. However, AB48-R’s sensitivity to antibiotics such as cefepime, gentamicin, amikacin, and tobramycin increased, indicating an evolutionary trade-off. Conclusions Phage HZY2308 shows strong antimicrobial potential, especially in combination with tigecycline, and the phage-resistant strain exhibits increased antibiotic sensitivity.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

In this study, Ce2[Zr1−x(Ba1/3Nb2/3)x]3(MoO4)9 (0.02 ≤ x ≤ 0.1, CZ1−xNx) ceramics were sintered at 600 °C and 700 °C using the traditional solid-state method. An analysis conducted through XRD and Rietveld refinement confirmed that all the CZ1−xNx ceramics displayed a single phase with a trigonal structure (space group R-3c). The observed increases in cell volume with increasing x values indicate the successful substitution of (Ba1/3Nb2/3)4+. The high densification of the synthesized phase was validated by the density and SEM results. Additionally, the P-V-L theory demonstrates a strong correlation between the Ce-O bond and εr, as well as τf, and between the Mo-O bond and Q×f. Notably, the CZ0.98N0.02 ceramics demonstrated superior performance at 675 °C, exhibiting εr = 10.41, Q×f = 53,296 GHz, and τf = −23.45 ppm/°C. Finally, leveraging CZ0.98N0.02 ceramics as substrate materials enabled the design of a patch antenna suitable for the 5G communication band, demonstrating its significant potential in this field.

Background: Synthetic lethality (SL) emerges as a novel concept being explored to combat cancer progression and resistance to conventional therapy. Despite the efficacy of chemotherapy in select cases of colorectal cancer (CRC), a substantial proportion of patients encounter challenges, leading to an adverse prognosis of CRC patients. CRC-related SL genes offer a potential avenue for identifying therapeutic targets. Methods: CRC-related SL genes were obtained from the SynLethDB database. The bulk RNA sequencing data, mutation data, and clinical information for treated and untreated CRC patients were enrolled from the UCSC and GEO databases. The Tumor Immunology Single Cell Center database served as the repository for collecting and analyzing single-cell RNA sequencing data. The synergistic killing effect of SL genes and chemotherapeutic drugs on resistant cells was experimentally verified. Results: In the present study, pivotal SL genes associated with chemoresistance identified by using WGCNA and CRC patients categorized into two groups based on these genes. Variations between the groups were most pronounced in pathways associated with extracellular matrix remodeling. Further by integrating mutation data, five potential SL genes were discerned, which were highly expressed in the presence of TP53 or KRAS mutations, leading to a severely poor prognosis. Subsequent time series analysis revealed that the expression of GTF2H5 was gradually elevated at different stages of the transition from sensitive to resistant in CRC cells. Finally, it was preliminarily verified by experiments that GTF2H5 may play a key role in driving the drug-resistant transition within CRC cells. Conclusions: The identification of SL genes that collaboratively interact with chemotherapeutic agents could provide new insights into solving the issue of chemotherapy resistance in CRC patients. And GTF2H5 wields a fundamental influence in inducing chemoresistance in CRC, which provided a potential therapeutic target for CRC.

BackgroundOsteoarthritis (OA) is a degenerative disease with a high incidence worldwide. Most affected patients do not exhibit obvious discomfort symptoms or imaging findings until OA progresses, leading to irreversible destruction of articular cartilage and bone. Therefore, developing new diagnostic biomarkers that can reflect articular cartilage injury is crucial for the early diagnosis of OA. This study aims to explore biomarkers related to the immune microenvironment of OA, providing a new research direction for the early diagnosis and identification of risk factors for OA.MethodsWe screened and downloaded relevant data from the Gene Expression Omnibus (GEO) database, and the immune microenvironment-related genes (Imr-DEGs) were identified using the ImmPort data set by combining weighted coexpression analysis (WGCNA). Functional enrichment of GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted to explore the correlation of Imr-DEGs. A random forest machine learning model was constructed to analyze the characteristic genes of OA, and the diagnostic significance was determined by the Receiver Operating Characteristic Curve (ROC) curve, with external datasets used to verify the diagnostic ability. Different immune subtypes of OA were identified by unsupervised clustering, and the function of these subtypes was analyzed by gene set enrichment analysis (GSVA). The Drug-Gene Interaction Database was used to explore the relationship between characteristic genes and drugs.ResultsSingle sample gene set enrichment analysis (ssGSEA) revealed that 16 of 28 immune cell subsets in the dataset significantly differed between OA and normal groups. There were 26 Imr-DEGs identified by WGCNA, showing that functional enrichment was related to immune response. Using the random forest machine learning model algorithm, nine characteristic genes were obtained: BLNK (AUC = 0.809), CCL18 (AUC = 0.692), CD74 (AUC = 0.794), CSF1R (AUC = 0.835), RAC2 (AUC = 0.792), INSR (AUC = 0.765), IL11 (AUC = 0.662), IL18 (AUC = 0.699), and TLR7 (AUC = 0.807). A nomogram was constructed to predict the occurrence and development of OA, and the calibration curve confirmed the accuracy of these 9 genes in OA diagnosis.ConclusionThis study identified characteristic genes related to the immune microenvironment in OA, providing new insight into the risk factors of OA.

ABSTRACT The management of Pseudomonas aeruginosa (P. aeruginosa) infections presents a substantial challenge to clinics and public health, emphasizing the urgent need for innovative strategies to address this issue. Quorum sensing (QS) is an intercellular communication mechanism that coordinates bacterial activities involved in various virulence mechanisms, such as acquiring host nutrients, facilitating biofilm formation, enhancing motility, secreting virulence factors, and evading host immune responses, all of which play a crucial role in the colonization and infection of P. aeruginosa. The LasI/R and RhlI/R sub-systems dominate in the QS system of P. aeruginosa. Macrophages play a pivotal role in the host’s innate immune response to P. aeruginosa invasion, particularly through phagocytosis as the initial host defense mechanism. This study investigated the effects of P. aeruginosa’s QS system on THP-1 macrophages. Mutants of PAO1 with lasI/rhlI deletion, as well as their corresponding complemented strains, were obtained, and significant downregulation of QS-related genes was observed in the mutants. Furthermore, the ΔlasI and ΔlasIΔrhlI mutants exhibited significantly attenuated virulence in terms of biofilm formation, extracellular polymeric substances synthesis, bacterial adhesion, motility, and virulence factors production. When infected with ΔlasI and ΔlasIΔrhlI mutants, THP-1 macrophages exhibited enhanced scavenging ability against the mutants and demonstrated resistance to cytotoxicity, oxidative stress, inflammatory response, and apoptosis induced by the culture supernatants of these mutant strains. These findings offer novel insights into the mechanisms underlying how the lasI/rhlI mutation attenuates cytotoxicity, oxidative stress, inflammation, and apoptosis in macrophages induced by P. aeruginosa.IMPORTANCEP. aeruginosa is classified as one of the ESKAPE pathogens and poses a global public health concern. The QS system of this versatile pathogen contributes to a broad spectrum of virulence, thereby constraining therapeutic options for serious infections. This study illustrated that the lasI/rhlI mutation of the QS system plays a prominent role in attenuating the virulence of P. aeruginosa by affecting bacterial adhesion, biofilm formation, extracellular polymeric substances synthesis, bacterial motility, and virulence factors’ production. Notably, THP-1 macrophages infected with mutant strains exhibited increased phagocytic activity in eliminating intracellular bacteria and enhanced resistance to cytotoxicity, oxidative stress, inflammation, and apoptosis. These findings suggest that targeted intervention toward the QS system is anticipated to diminish the pathogenicity of P. aeruginosa to THP-1 macrophages.

Acute Liver Injury (ALI), a highly prevalent liver disease in the last two decades, but there is still no effective treatment for it. As a member of Tibetan medicine, Swertia chirayita is commonly used for treating liver-related diseases, while the behavior of S. chirayita in CCl4-induced ALI is deficient. In this work, the chemical constituents of S. chirayita were identified using a UPLC-Q-Exactive Orbitrap MS method. And the potential targets of the active compound of S. chirayita in CCl4-induced ALI have been explored on the basis of bioinformatics analysis and ALI model. The findings revealed that a total of 49 compounds have been identified in S. chirayita, and 10 have been absorbed into blood as prototypes. Network pharmacology and molecular docking studies have shown that S. chirayita has a multi-component, multi-target profile for the treatment of CCl4-induced ALI. Biochemical indicators testing demonstrated that Swertiamarine (STW) improved the levels of AST, ALT, MDA, SOD, TNF-α and IL-6 in CCl4-induced ALI mouse model. Additionally, H&E staining indicated that STW significantly improved cellular necrosis, inflammatory infiltration, and other forms of pathological liver damage in mice. Meanwhile, quantitative reverse transcription PCR (qRT-PCR) showed that STW could ameliorate CCl4-induced ALI by regulate the expression of EGFR, CASP3, STAT3 and other targets. In conclusion, as one of the active compounds of S. chirayita, STW could alleviate ALI by modulating the expression of biochemical indicators, liver pathological indicators and critical targets. This will provide a theoretical basis for the further research and development of the S. chirayita.

Summary: Background: Internet exclusion and depressive symptoms are prevalent phenomena among older adults; however, the association between internet exclusion and depressive symptoms remains limited. This study aims to investigate the association between internet exclusion and depressive symptoms among older adults from high-income countries (HICs) and low- and middle-income countries (LMICs). Methods: We conducted a comprehensive longitudinal, cross-cultural analysis, and the participants were adults aged 60 years and older from 32 countries participating in five nationally representative longitudinal cohort studies: the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), the China Health and Retirement Longitudinal Study (CHARLS), and the Mexican Health and Ageing Study (MHAS). Internet exclusion was defined as the self-reported absence from internet use. Depressive symptoms were evaluated using the Centre for Epidemiologic Studies of Depression scale (CES-D) or the Euro-Depression scale (Euro-D). These five cohorts, being heterogeneous, were respectively conducted with panel data analysis. Logistic regression, implemented within the generalized estimating equations framework, was used to examine the association between internet exclusion and the likelihood of experiencing depressive symptoms, adjusting for the causal-directed-acyclic-graph (DAG) minimal sufficient adjustment set (MSAS), including gender, age, education, labour force status, household wealth level, marital status, co-residence with children, residence status, cognitive impairment, and functional ability. Findings: Our study included a total of 129,847 older adults during the period from 2010 to 2020, with a median follow-up of 5 (2, 7) years. The pooled proportion of internet exclusion was 46.0% in HRS, 32.6% in ELSA, 54.8% in SHARE, 92.3% in CHARLS, and 65.3% in MHAS. Internet exclusion was significantly associated with depressive symptoms across all cohort studies: HRS (OR = 1.13, 95% CI 1.07–1.20), ELSA (OR = 1.22, 95% CI 1.11–1.34), SHARE (OR = 1.55, 95% CI 1.47–1.62), CHARLS (OR = 1.49, 95% CI 1.26–1.77), and MHAS (OR = 1.48, 95% CI 1.39–1.58). Moreover, internet exclusion was found to be associated with all dimensions of depression in the SHARE, MHAS, and ELSA cohorts (except for sleep and felt sad) cohorts. Interpretation: A considerable proportion of older adults experienced internet exclusion, particularly those in LMICs. Internet exclusion among older adults, irrespective of their geographic location in HICs or LMICs, was associated with a higher likelihood of experiencing depressive symptoms, which demonstrated the importance of addressing barriers to internet access and promoting active participation in the internet society among older adults. Funding: National Key R&D Program of China (grant number 2022ZD0160704), the Scientific Research and Innovation Team of The First Affiliated Hospital of Zhengzhou University (grant number ZYCXTD2023005), the Collaborative Innovation Major Project of Zhengzhou (grant number 20XTZX08017), the Joint Project of Medical Science and Technology of Henan Province (grant number LHGJ20220428), and National Natural Science Foundation of China (grant number 82373341).

Introduction: Breast cancer (BC) is a malignant disease that occurs worldwide and poses serious health burden. Objectives: To assess the prevalence of BC burden in the Western Pacific region (WPR) from 1990 to 2019, and to predict trends from 2020 to 2044. To analyze the driving factors and put forward the region-oriented improvement. Methods: Based on the Global Burden of Disease Study 2019, BC cases, deaths, disability-adjusted life years (DALYs) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate in WPR from 1990 to 2019 was obtained and analysed. Age-period-cohort (APC) model was used to analyze age, period, and cohort effects in BC, and Bayesian APC (BAPC) was used to predict trends over the next 25 years. Results: In conclusion, BC incidence and deaths in the WPR have increased rapidly over the past 30 years and are expected to continue to increase between 2020 and 2044. Among behavioral and metabolic factors, high body-mass index was the main risk factor for BC mortality in middle-income countries, whereas alcohol use was the main risk factor in Japan. Age is a key factor in the development of BC, with 40 years being the critical point. Incidence trends coincide with the course of economic development. Conclusions: The BC burden remains an essential public health issue in the WPR and will increase substantially in the future. More efforts should be made in middle-income countries to prompt the health behavior and minimize the burden of BC because these nations accounts for the majority of BC burden in the WPR.

【Objective】The digitization of agriculture and rural areas is considered to be a crucial element in promoting rural revitalization and enhancing agricultural construction, significantly contributing to the increase of farmers' income. The study aims to develop an comprehensive framework for evaluating the digitization of agriculture and rural areas, empirically investigating its effectiveness in income increase and clarifying the action mechanisms. Additionally, it provides policyoriented insights to alleviate the challenges of the "digital divide" and to advance the sophisticated development of the digital economy in agricultural and rural areas.【Methods】The panel data from 31 provinces (region) in China from 2011-2020 was selected, and the Entropy-Weighted TOPSIS Method was applied for assessing the level of digitalization in agriculture and rural areas. The fixed and mediation effects were utilized to investigate the influence and mechanisms of digitalization on farmers'income increase. A threshold model was employed to explore the threshold effects between the digitalization and the increase of farmers' income.【Results】(1) Digitalization in agriculture and rural areas significantly enhances farmers' income; with a 1% increase in digitalization level corresponding to an average income increase of 57.4 CNY for farmers. The positive effect is more pronounced in the eastern regions, while it appears to be inhibitory in the central regions and less evident in promoting income in the western regions, indicating the presence of a "digital divide". (2) Digitalization in agriculture and rural areas contributes to farmers' income increase through multiple channels: fostering diversification of farmers' occupations, accelerating land circulation, enhancing the probability of farmers obtaining financing, and promoting the sales of agricultural products. (3) Digital inclusive finance exhibits significant dual threshold effects between digitalization in agriculture and rural areas and farmers' income increase, with the first threshold value at 33.401 and the second at 148.370. As the threshold interval increases, the impact of digitalization on farmers' income increase demonstrates a "positive U-shaped" relationship, showing as initially inhibitory and subsequently promotive.【Conclusion】Digitalization in agriculture and rural areas effectively facilitates income increase for farmers, however, the challenges of the "digital divide" persist. Consequently, it proposes policy implications such as enhancing digital infrastructure, providing training and education in agricultural digitalization, promoting the development of rural digital inclusive finance, and formulating region-specific digital development strategies to further augment farmers' income.

Abstract Plants of the Tamarix L. genus (Tamaricaceae) mainly occur in arid inlands of Asia, but a few species occur in the coastal areas of China, and the Yellow River may account for this. This study was conducted to elucidate whether and how the Yellow River affects the pattern and development of the Tamarix genus, involving two critical species of Tamarix austromongolica Nakai and Tamarix chinensis Lour. With geographical distribution data, relationships of T. austromongolica with the Yellow River and the pertaining watershed were examined using the method of random permutation. The base‐diameter structures of T. austromongolica populations were investigated and compared between different riparian lands that suffer discriminative water inundation. The nearest distances from T. austromongolica locations to the Yellow River and the pertaining watershed were significantly lower than the theoretical expectations in the condition of random distribution (p

Background Embankment dams were built south of the Laizhou bay in China for controlling storm surge disasters, but they are not enough to replace coastal forests in protecting the land. This study was designed to evaluate the effects of embankment dams on natural forests dominated by Tamarix austromongolica and test whether the dam-shrub system is a preferable updated defense. Methods Coastal forests on two typical flats, one before and one behind embankment dams, were investigated using quadrats and lines. Land bareness, vegetation composition and species co-occurrence were assessed; structures of T. austromongolica populations were evaluated; and spatial patterns of the populations were analyzed using Ripley’s K and K1,2 functions. Results In the area before embankment dams, 84.8% of T. austromongolica were juveniles (basal diameter ≤ 3 cm), and 15.2% were adults (basal diameter > 3 cm); behind the dams, 52.9% were juveniles, and 47.1 were adults. In the area before the dams, the land bareness was 13.7%, four species occurred, and they all were ready to co-occur with T. austromongolica; behind the dams, the land bareness was 0%, and 16 species occurred whereas they somewhat resisted co-occurrence with T. austromongolica. In the area before the dams, the T. austromongolica population was aggregated in heterogeneous patches, and the juveniles tended to co-occur with the adults; behind the dams, they were over-dispersed as nearly uniform distributions, while the juveniles could recruit and were primarily independent of the adults. These results indicate that the T. austromongolica species did not suffer from the unnatural dams, but benefited somehow in population expansion and development. Overall, the T. austromongolica species can adapt to artificial embankment dams to create a synthetic defense against storm surges.

ObjectiveUtilize VUEBOX quantitative analysis software to perform quantitative analysis dynamic ultrasound contrast images of post-transplant renal patients were assessed quantitatively five parameters of ultrasonic contrast and two-dimensional ultrasound are examined to explore their six value in Diagnosing Renal Graft Dysfunction.MethodsA retrospective analysis was conducted on 73 post-transplant renal patients who underwent ultrasound contrast examinations at Yiyang Central Hospital from July 2022 to December 2023, They were diagnosed clinically and pathologically. Based on pathological and clinical diagnostic results, the patients were divided into three groups: 47 cases in the stable renal function group, 18 cases in the acute rejection (AR) group, and 8 cases in the delayed graft function (DGF) group. All patients underwent routine ultrasound and ultrasound contrast examinations post-transplantation. By comprehensively assessing renal function test results, clinical course, and pathological findings, differences in ultrasonic contrast quantitative parameters were analyzed. Additionally, ROC curves were constructed to evaluate the diagnostic efficacy of ultrasound contrast in discriminating between transplant renal rejection reactions and delayed renal function recovery.ResultsStatistically significant differences in characteristics, such as renal segmental artery resistance index, were observed among the stable renal function group, AR group, and DGF group (all P < 0.05), while peak systolic velocity showed no statistical significance (P > 0.05). Differences in cortical time to peak (TTP), medullary time to peak(TTP), main renal artery rise time (RT), main renal artery(TTP), and main renal artery fall time (FT) were statistically significant among the stable renal function group, AR group, and DGF group (P < 0.05). ROC curve analysis demonstrated that the accuracy of quantitative parameters for the DGF group and AR group was as follows: Renal artery TTP = Renal artery RT > Renal artery FT > Medulla TTP > Cortex TTP (with respective area under the curve values of 0.828, 0.828, 0.758, 0.742, 0.719). Among these, Renal artery TTP and Renal artery RT exhibited larger AUC values, with sensitivities of 87.5% each and specificities of 81.2 and 87.5%, respectively.ConclusionThere are discernible differences in VUEBOX quantitative parameters between post-transplant AR and DGF cases, thereby providing imaging references for diagnosing of acute rejection and functional impairment following renal transplantation.

Summary: CD8+ T cells are rendered exhausted in tumor and chronic infection. Among heterogeneous exhausted T cells, a subpopulation of progenitor-like (Tpex) cells have been found important for long-term tumor or pathogen control and are also the main responders in immunotherapy. Using an RFP reporter mouse for the orphan nuclear receptor NR4A1, originally characterized as critical in T cell dysfunction, we discover that the reporter is highly expressed in Tpex cells in tumor and chronic infection. Enforced expression of Nr4a1 promotes Tpex cell accumulation, whereas tumor control is improved after Nr4a1 deletion, associated with increased effector function but decreased long-term maintenance of CD8+ T cells. Integrating chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, NR4A1 is found to bind and promote the expression of Tpex-related genes, as well as suppress terminal differentiation-associated genes. This study therefore has identified a key role of NR4A1 in Tpex regulation and provides a promising target for immunotherapy.

Face Presentation Attack Detection (PAD) is critical for enhancing the security of facial recognition systems against sophisticated attacks. This study explores the use of general Image Quality Assessment (IQA) methods in face PAD, offering an alternative strategy that deviates from traditional, face-specific PAD techniques. Our evaluation of eight widely-used IQA methods across four PAD databases is structured around three distinct experimental protocols. Preliminary findings indicate that the general IQA methods are not fully effective in differentiating between genuine and attack samples, highlighting the need for modification. Nonetheless, a notable enhancement in performance is observed following the re-training of these methods using PAD datasets, bringing their effectiveness in line with that of advanced traditional PAD methods. This study provides evidence for the potential of general IQA in bolstering the resilience of face recognition systems against presentation attacks.

Objectives: Excessive reactive oxygen species (ROS) in diabetic wounds are major contributors to chronic wounds and impaired healing, posing significant challenges in regenerative medicine. Developing innovative drug delivery systems is crucial to address these issues by modifying the adverse microenvironment and promoting effective wound healing. Methods: Herein, we designed a novel drug delivery platform using manganese dioxide nanoflower hybridized gold nanoparticle composites (MnO2-Au) synthesized via a hydrothermal reaction, and investigated the potential of MnO2-Au nanoflowers to relieve the high oxidative stress microenvironment and regulate diabetic wound tissue healing. Results: This hybrid material demonstrated superior catalytic activity compared to MnO2 alone, enabling the rapid decomposition of hydrogen peroxide and a substantial reduction in ROS levels within dermal fibroblasts. The MnO2-Au nanoflowers also facilitated enhanced dermal fibroblast migration and Col-I expression, which are critical for tissue regeneration. Additionally, a hydrogel-based wound dressing incorporating MnO2-Au nanoflowers was developed, showing its potential as an intelligent drug delivery system. This dressing significantly reduced oxidative stress, accelerated wound closure, and improved the quality of neonatal epithelial tissue regeneration in a diabetic rat skin defect model. Conclusions: Our findings underscore the potential of MnO2-Au nanoflower-based drug delivery systems as a promising therapeutic approach for chronic wound healing, particularly in regenerative medicine.

More than half of the carbon pools in peatlands are stored in the soil layers below 30 cm, yet little is known about the carbon stabilizing factors at these depths. Although iron oxide minerals are considered to be important for stabilizing organic carbon (OC), their role in the preservation of OC in peatlands, especially in the deep layers, is poorly understood. Here, we collected 1 m soil profiles from six peatlands in Central and West China to quantitatively study the vertical distribution characteristics of iron-bound OC (Fe-bound OC), and the influencing physicochemical properties of the soil. The results showed that the content of reactive iron (FeR) was enriched in the top layer and decreased gradually with depth. While Fe-bound OC was positively correlated with FeR, its concentration did not decrease with depth in the peat profile. There were no obvious trends in the distributions of FeR and Fe-bound OC with water level fluctuations in the peat profile. In addition, the proportion of Fe-bound OC to soil organic carbon in the deep peat (31 to 100 cm) was equivalent to that in the surface peat (0 to 30 cm), indicating that iron oxide mineral provides comparable protection of OC in both layers. According to upper estimates of global peatland carbon storage (612 Pg), it could be predicted that 23.81 ± 11.75 Pg of OC is protected by association with FeR. These results indicated that iron oxide minerals are the effective ''rusty sink'' of OC sequestration in peatland, and a key factor for its long-term preservation. The results from this study make a valuable contribution to the carbon dynamics knowledgebase for peatlands, and provide a basis for improved predictive simulations.

Abstract Background Ankle sprain are one of the most frequent sports injuries. Some individuals will develop chronic lateral ankle instability (CLAI) after ankle sprain and suffer from recurrent ankle sprain. Current surgical treatment of CAI with anterior talofibular ligament (ATFL) rupture fails to restore the stability of the native ATFL. Ligament Advance Reinforcement System (LARS) augmentation repair of ATFL was developed to improve its primary stability after repaired. Methods This study was performed to evaluate whether LARS augmentation repair of ATFL had similar stability as the modified Broström repair and the intact ATFL to maintain ankle construct stability. Standardized surgical techniques were performed on eighteen fresh frozen cadaver ankle specimens. The intact ATFL group has just undergone an ATFL exploratory surgery. The modified Broström procedure is based on anatomical repair of the ATFL with a 2.9 mm suture anchor, and the LARS procedure is an augmentation procedure of the ATFL using LARS ligaments based on the modified Broström procedure. A dynamic tensile test machine was used to assess load-to-failure testing in the three groups. The ultimate failure load and stiffness were calculated and reported from the load-displacement curve. A one-way analysis of variance was used to detect significant differences (p

This study investigated the influence of green manure planting on the spectroscopic properties of dissolved organic matter (DOM) in saline–alkali soil under freshwater leaching conditions at different soil depths. The UV254, UV253/UV203, α300, α355, SUVA254, SUVA260, and SR ultraviolet parameters indicated reductions in the content of large molecular substances, benzene ring substitution degree, colored dissolved organic matter, aromaticity, and hydrophobic components in the soil leachate DOM with an increasing soil depth. Compared with the non-green manure treatment control, green manure planting mitigated the leaching of dissolved organic matter in soil during saline irrigation, with rape green manure demonstrating superior effectiveness. Utilizing three-dimensional fluorescence combined with parallel factor analysis, this study analyzed three fluorescent components of soil leachate DOM: C1 (visible-light fulvic acid), C2 (humic acid), and C3 (tyrosine-like protein). The combined contribution of the two humic substance components (C1 + C2) was approximately 70%, indicating the dominance of humic substances in leachate DOM. The fluorescence parameters of soil leachate DOM included an average of the fluorescence index (FI) values between 1.4 and 1.9, low humification index (HIX) values consistently below 4, and biological index (BIX) values ranging from 0.8 to 1.0, suggesting a mixed source, low humification degree, poor stability, and moderate self-source characteristics. Compared with the non-green manure treatment control, both the green manure treatments exhibited a relatively higher proportion of biogenic sources and humification degree in soil leachate DOM. This suggests that planting green manure can reduce the relative DOM content under freshwater leaching conditions, increase the proportion of biogenic sources in soil leachate DOM, and enhance soil humification. Planting rapeseed green manure can diminish the leaching of DOM from land sources and augment soil humification.

ObjectiveTo explore spatiotemporal non-stationarity in health poverty prevalence and its influencing factors among middle-aged and elderly residents in China for providing evidence to promote comprehensive and effective management on health poverty alleviation in the populations. MethodsThe data of the analysis were extracted from four rounds of China Health and Retirement Longitudinal Survey (CHARLS) conducted in 2011, 2013, 2015, and 2018 across China, which collected the information on 37 296 households with family members aged ≥ 45 years. Other relevant data were extracted from the China Statistical Yearbook of 2012, 2014, 2016, and 2019, the China Health and Family Planning Statistical Yearbook of 2012 and 2016, the China Tertiary Industry Statistical Yearbook of 2014 and 2019, and from the Global Burden of Disease Network in 2019. Based on the self-developed indexes for measurement of multidimensional health poverty (MHP), we used the ordinary least squares model (OLS), the geographically weighted regression model (GWR), the temporally weighted regression model (TWR), and the geographically and temporally weighted regression model (GTWR) to model the impacts of influencing factors on health poverty among the middle-aged and elderly residents during the period. The spatiotemporal modes of the estimation coefficients in the optimal model were further described. ResultsAfter adjusting for fixed effects of year and region, the global OLS regression results showed that the MHP index increased with the increment of the prevalence of non-communicable diseases (NCDs) and disabilities, gross domestic production (GDP) per capita, average out-of-pocket medical expenditure, and mean annual concentration of particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5) in previous 3 years; but the index decreased with the increment of population density, the coverage of basic medical insurance, and the number of nurses per 10 000 population. Among all partial regression models constructed, GWR fitted the survey data best, with the increased R2 from 70.57% to 88.68% and the decreased sum of squares of the residuals from 797.791 to 585.277 compared with the global OLS regression model. The impacts of the eight covariates mentioned above on MHP index were non-stationary based on the results of GWR modeling; the aggravating impact of NCDs prevalence rate on MHP index was much stronger for Inner Mongolia Autonomous Region (Inner Mongolia) and the four provinces including Hebei, Shanxi, Yunnan, and Guizhou; the aggravating impact of disability prevalence rate on MHP index was much more stronger for Jiangsu, Anhui, and Henan province; the alleviating impact of population density on MHP index was stronger for the five provinces of Heilongjiang, Jilin, Liaoning, Shandong, and Shanxi and much more stronger for Inner Mongolia, Gansu and Hebei provinces, and Beijing municipality; both the alleviating impact of the coverage rate of basic medical insurance and the number of nurses versus 10 000 population and the aggravating impact of GDP per capita on MHP index were the strongest for Xinjiang Uygur Autonomous Region, Qinghai province, and Gansu province; the aggravating impact of average out-of-pocket medical expenditure on MHP index was much more stronger for Henan, Anhui and Jiangsu province; the aggravating impact of mean annual PM2.5 concentration in previous 3 years on MHP index attenuated gradually from a central region including Beijing municipality, Hebei province and Inner Mongolia to the surrounding area of whole Bohai rim region. ConclusionThere is a spatial non-stationarity for the impacts of multiple factors on health poverty among middle-aged and elderly residents in China. Partial weighted regression analysis could be adopted to examine the non-stationarity in studies on improving administrative efficiency of regional health poverty reduction.

The negative overlap and cycle between disease and poverty outcomes and burdens have become a core driver of existing poverty in China, and constitute an essential characteristic factor of health poverty. Compared to economic and cultural poverty, health poverty has become a key constraint in the fight against poverty, and an important risk and challenge in sustaining China′s achievements in the post-poverty reduction era. With bibliometrics method, qualitative expert interview and using social network analysis, we define and explain the connotation and characteristics of multidimensional health poverty from multiple perspectives of disease, economy, culture and education, and governance system; we also try to construct a theoretical model of health poverty involving three dimensions: health capacity, health right, and health risk and deconstruct the action mechanisms of the three aspects in the occurrence, expansion, continuation, and elimination of health poverty.

ObjectiveTo measure multidimensional health poverty (MHP) and its urban-rural disparity among Chinese households for providing evidence to the elimination of health poverty among urban and rural households in China. MethodsThe data of the analysis were extracted from a round of China Family Panel Survey (CFPS) conducted in 2018 across China, which collected the information of 12 494 households (6 409 in urban and 6 085 in rural regions) on economic activity, education access, family relationship and dynamics, migration, and family members' physical and mental health status. The MHP was assessed and the contribution of the three dimensional components (health right, health capability and health risk) to MHP were deconstructed with self-established health poverty evaluation index system and multidimensional health poverty measurement index (MHPI). ResultsFor all the households surveyed in 2018, the overall MHPI was 0.216 and the prevalence of MHP was 0.472; the values of MHPI and MHP prevalence were 0.184 and 0.410 for the surveyed urban households but were 0.249 and 0.537 for the rural households. For the households surveyed nationwide, in urban regions, and in rural regions, the contribution indexes of health risk/capability/right to MHP were 0.478/0.268/0.254, 0.267/0.268/0.505, and 0.244/0.299/0.457, respectively. ConclusionDuring 2018 in China, both the MHPI and MHP prevalence were higher in rural households than those in urban households; health risk was an important contributor to MHP and the urban-rural disparity in the contribution of health capacity to MHP was the greatest among the three dimensional contributors of MHP.

ObjectiveTo examine spatial and temporal distribution patterns of household-based multidimensional health poverty (MHP) indexes among middle-aged and elderly populations in China, and to provide evidence to precise elimination of MHP in the populations. MethodsThe data of the analysis were extracted from four rounds of China Health and Retirement Longitudinal Survey (CHARLS) conducted in 2011, 2013, 2015, and 2018 across China, which collected the information of residents aged ≥ 45 years in 37 296 households on demographics, income and consumption, family structure, economic support, health status, health service utilization and medical insurance. The MHP was assessed and deconstructed with self-established health poverty evaluation index system and multidimensional health poverty measurement index (MHPI) covering three dimensional components (health right, health capability and health risk) of MHP. The year- and region-specific distribution of MHPI were described. ResultsFor all the middle-aged and elderly residents surveyed in 2011, 2013, 2015, and 2018, the health MHPI were 0.320, 0.326, 0.349, and 0.29 and the MHP prevalence were 69.7%, 69.0%, 71.9%, and 63.0%, respectively. The mean values of index measuring the contribution of health right, health capacity and health risk to MHP were 0.143, 0.450 and 0.416 for all the residents surveyed in the four rounds of CHARLS study. The results of regional decomposition analysis on MHPI showed that following six provincial-level administrative divisions (PLADs) could be assessed as with severe prevalence of health poverty in 2011: Guizhou, Gansu, Xinjiang Uygur Autonomous Region (Xinjiang), Sichuan, Anhui, and Jilin, with the mean MHPI of 0.365, 0.364, 0.395, 0.377, 0.402, and 0.413,respectively; in 2013, the six PLADs assessed as having severe prevalence of health poverty were Yunnan, Qinghai, Inner Mongolia Autonomous Region (Inner Mongolia), Sichuan, Anhui, and Guizhou and the mean MHPI for those PLADs were 0.359, 0.361, 0.381, 0.378, 0.389, and 0.402; while in 2015 the number of PLADs with severe prevalence of health poverty increased to 16, including Yunnan (mean MHPI = 0.395), Xinjiang (0.388), Qinghai (0.448), Sichuan (0.406), Inner Mongolia (0.39), Anhui (0.388), Chongqing (0.391), Guizhou (0.373), Tianjin (0.370), Heilongjiang (0.366), Guangxi (0.362), Shandong (0.362), Jiangxi (0.359), Jilin (0.355), Fujian (0.351), and Liaoning (0.350); but in 2018, only 3 PLADs (Sichuan, Guizhou, and Yunnan, with the mean MHPI of 0.352, 0.352, and 0.351) could be assessed as with severe prevalence of health poverty. ConclusionAccording to this analysis, both mean index and prevalence of health poverty declined generally among middle-aged and elderly populations in China during 2011 – 2018; there were regional differences in health poverty prevalence and the multidimensional health poverty was more severe in southwest region.

Summary: Climate change and human activities have intensified variations of water table depth (WTD) in wetlands around the world, which may strongly affect greenhouse gas emissions. Here, we analyzed how emissions of CO2, CH4, and N2O from the Zoige wetland on the Qinghai-Tibetan Plateau (QTP) vary with the WTD. Our data indicate that the wetland shows net positive global warming potential (11.72 tCO2-e ha−1 yr−1), and its emissions of greenhouse gases are driven primarily by WTD. Our analysis suggests that an optimal WTD exists, which at our study site was approximately 18 cm, for mitigating increases in global warming potential from the wetland. Our study provides insights into how climate change and human acitivies affect greenhouse gas emissions from alpine wetlands, and they suggest that water table management may be effective at mitigating future increases in emissions.

Abstract Background The transmission of 2019 novel coronavirus (COVID-19) has caused global panic in the past three years. Countries have learned an important lesson in the practice of responding to COVID-19 pandemic: timely and accurate diagnosis is critical. As an important technology of virus diagnosis, nucleic acid testing (NAT) is also widely used in the identification of other infectious diseases. However, geographic factors often constrain the provision of public health services such as NAT services, and the spatial nature of their resource allocation is a significant problem. Methods We used OLS, OLS-SAR, GWR, GWR-SAR, MGWR, and MGWR-SAR models to identify the determinants of spatial difference and spatial heterogeneity affecting NAT institutions in China. Results Firstly, we identify that the distribution of NAT institutions in China shows a clear spatial agglomeration, with an overall trend of increasing distribution from west to east. There is significant spatial heterogeneity in Chinese NAT institutions. Secondly, the MGWR-SAR model results show that city level, population density, number of tertiary hospitals and number of public health emergency outbreaks are important factors influencing the spatial heterogeneity of NAT institutions in China. Conclusions Therefore, the government should allocate health resources rationally, optimise the spatial layout of testing facilities, and improve the ability to respond to public health emergencies. Meanwhile, third-party testing facilities need to focus on their role in the public health emergency response system as a market force to alleviate the inequitable allocation of health resources between regions. By taking these measures to prepare adequately for possible future public health emergencies.

Grasping the interrelationship between the supply and demand of ecosystem services (ESs) and spatial scale characteristics is the foundation for effective ecological zoning management, which helps to realize a win–win situation for both ecological protection and economic development. This paper focuses on the following three real problems: mismatch in ES supply and demand evaluation, mechanical and subjective delineation of ecological zoning, and rough management strategies, and constructs a multi-scale ecological zoning management framework for the “comprehensive evaluation of supply and demand, ecological zoning, and enhancement of human well-being”. This study integrates the InVEST model, SOM, Z-score quadrant matching, and coordination degree method, and applies them to the ecological management zoning of Hangzhou. The results show that (1) the spatial differentiation of ESs in Hangzhou is significant. The spatial pattern of the five types of ES supply varies at the county scale and the grid scale on which ES demand is concentrated and is consistent at different scales. (2) ES supply–demand matching in Hangzhou is at the basic coordination and can be divided into four modes including HH, LH, LL, and HL at both the county and grid scales. On the small scale, the proportion of mismatches declines slightly, but the severity rises. (3) ES supply is divided into four categories as follows: the food production bundle, the carbon storage bundle, the ESs balancing bundle, and the ESs depleting bundle, and clarifies the priority of ES management. (4) Construct an ecological management practice path, delineates 6 ecological management zones at the county scale and 19 secondary management zones at the grid scale. Targeted measures are proposed in terms of supply–demand adjustment strategies, ecological management strategies, and key implementation areas. This study helps to incorporate the interaction between the supply and demand of ESs into the planning framework and provides decision-making support for refined ecological management.

Pseudomonas aeruginosa is a clinically common conditionally pathogenic bacterium, and the abuse of antibiotics has exacerbated its drug resistance in recent years. This has resulted in extensive reports about the usage of Pseudomonas aeruginosa phage as a novel antibacterial drug. In this study, we isolated a novel phage HZ2201 with a broad lytic spectrum. The lytic rate of this phage against Pseudomonas aeruginosa reached 78.38% (29/37), including 25 multi-drug- and carbapenem-resistant Pseudomonas aeruginosa strains. Transmission electron microscopy revealed that phage HZ2201 belongs to the class Caudoviricetes. Biological characterization showed that phage HZ2201 had an latent period of 40 min, a lytic period of 20 min, and a burst size of 440 PFU/cell, with improved tolerance to temperature and pH. Considering genomic analysis, the HZ2201 genome was a circular double-stranded DNA with a size of 45,431 bp and a guanine-cytosine (G + C) content of 52.16%, and contained 3 tRNAs. 27 of the 74 open reading frames (ORFs) annotated by the Rapid Annotation using Subsystem Technology (RAST) tool could be matched to the genomes of known functions, and no genes related to virulence and antibiotic resistance were found. The phylogenetic tree suggests that phage HZ2201 is highly related to the phage ZCPS1 and PaP3, and ORF57 and ORF17 are predicted to encode a holin and an endolysin, respectively. Cell lysis by HZ2201 proceeds through the holin-endolysin system, suggesting that it is a novel phage. Additionally, we demonstrated that phage HZ2201 has a high inhibitory capacity against Pseudomonas aeruginosa biofilms. The results of our study suggest that phage HZ2201 is a novel potential antimicrobial agent for treating drug-resistant Pseudomonas aeruginosa infection.

Stromal cells in the tumour microenvironment are reported to regulate cancer stemness via biomechanical signals. Here the authors show that TAZ activated by biomechanical cues enhanced cancer stem cell properties via phase separation with Nanog.

Abstract Background Organic materials carbon is mainly sequestrated in humin. However, the carbon (C) stability of humin with organic materials amendments in different types of soils is mainly affected by organic materials or soil types as well as the enzymatic reaction is important for understanding the C sequestration mechanism of soil. Results In this study, straw and straw-derived biochar were incorporated into three different types of soils. Using 13C nuclear magnetic resonance (NMR) spectroscopy, the structural composition of humin (Hu) was analyzed, along with the urease and β-glucosidase activities. The results showed that biochar amendment enhanced aryl C to 49.63%–76.55% while straw amendments increased O-alkyl C of Hu to 33.99%–51.70%. Two-way ANOVA analysis revealed significant differences in the impact of soil types and treatments on enzyme activities and functional groups of humin. A significant positive correlation was found between β-glucosidase activity and O-alkyl C, phenolic C, and methoxyl C of humin. In addition, urease activity showed a significant positive correlation with alkyl C of humin. Compared to tobacco straw, tobacco straw-biochar amendment increased β-glucosidase activity for 22.01 mg kg−1 d−1, 26.01 mg kg−1 d−1 and 14.01 mg kg−1 d−1 in three types of soils, respectively. Conclusions These results showed that β-glucosidase contributed to the transformation of humin functional groups and was influenced by organic materials and soil types, especially the organic materials types. The findings imply that straw or straw-derived biochar application stimulates urease and β-glucosidase activities, which improves the alternation of functional groups of humin in different types of soil. Graphical Abstract

Abstract Background China’s medical insurance schemes and poverty alleviation policy at this stage have achieved population-wide coverage and the system's universal function. At the late stage of the elimination of absolute poverty task, how to further exert the poverty alleviation function of the medical insurance schemes has become an important agenda for targeted poverty alleviation. To analyse the risk of catastrophic health expenditure (CHE) occurrence in middle-aged and older adults with vulnerability characteristics from the perspectives of social, regional, disease, health service utilization and medical insurance schemes. Methods We used data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database and came up with 9190 samples. The method for calculating the CHE was adopted from WHO. Logistic regression was used to determine the different characteristics of middle-aged and older adults with a high probability of incurring CHE. Results The overall regional poverty rate and incidence of CHE were similar in the east, central and west, but with significant differences among provinces. The population insured by the urban and rural integrated medical insurance (URRMI) had the highest incidence of CHE (21.17%) and health expenditure burden (22.77%) among the insured population. Integration of Medicare as a medical insurance scheme with broader benefit coverage did not have a significant effect on the incidence of CHE in middle-aged and older people with vulnerability characteristics. Conclusions Based on the perspective of Medicare improvement, we conducted an in-depth exploration of the synergistic effect of medical insurance and the poverty alleviation system in reducing poverty, and we hope that through comprehensive strategic adjustments and multidimensional system cooperation, we can lift the vulnerable middle-aged and older adults out of poverty.

The maturity degree of organic fertilizer affects its application effect, but this application effect difference and the underlying reasons for it remain largely unclear. This study explored the effects of cattle manure compost with different maturities on soybean yield, soil physicochemical properties, and biological properties, and the underlying reasons for the differences in the application effects of organic fertilizers with different maturities. The results showed that the T21d treatment (GI = 62.5%, germination index) had the optimal effect on increasing soybean yield, and its effect on improving basic soil physicochemical properties, active organic matter components, enzyme activity, and microbial diversity was the most obvious. Compared with the control (CK), the soybean yield was increased by 15.1% under T21d treatment, and the soil organic matter (OM), alkali-hydrolyzed nitrogen (AN), available phosphorus (AP), and available potassium (AK) contents were increased by 29.9%, 25.0%, 22.2%, and 8.4%, respectively; the dissolved organic matter (DOM), extractable humus (HE), humic acid (HA), and fulvic acid (FA) contents in the soil were increased by 96.5%, 22.6%, 16.7%, and 30.6%, respectively; and the activities of soil phosphatase, neutral protease, urease, and cellulase were increased by 45.4%, 164.1%, 33.9%, and 128.9%, respectively. However, the fertilizer efficiency under the T28d, T45d, and T60d treatments with high-maturity organic fertilizers was lower than that under T21d. In general, the appropriate maturity of organic fertilizers has a positive effect on soil improvement and yield increase, but the excessive maturity of organic fertilizers reduces their application effects.

Abstract Ferroptosis is a type of cell regulated necrosis triggered by intracellular phospholipid peroxidation, which is more immunogenic than apoptosis. Therefore, genes controlling ferroptosis may be promising candidate biomarkers for tumor therapy. In this study, we investigate the function of genes associated with ferroptosis in breast cancer (BC) and systematically evaluate the relationship between ferroptosis-related gene expression and prognosis of BC patients from the Cancer Genome Atlas database. By using the consensus clustering method, 1203 breast cancer samples were clustered into two clearly divided subgroups based on the expression of 237 ferroptosis-related genes. Then differentially expressed analysis and least absolute shrinkage and selection operator were used to identify the prognosis-related genes. Furthermore, the genetic risk signature was constructed using the expression of prognosis-related genes. Our results showed that the genetic risk signature can identify patient subgroups with distinct prognosis in either training cohort or validation, and the genetic risk signature was associated with the tumor immune microenvironment. Finally, the Cox regression analysis indicated that our risk signature was an independent prognostic factor for BC patients and this signature was verified by the polymerase chain reaction and western blot. Within this study, we identified a novel prognostic classifier based on five ferroptosis-related genes which may provide a new reference for the treatment of BRCA patients.

BackgroundPlasma cell mastitis (PCM) is a complex breast disease in the clinic. Currently, there are no unified diagnostic criteria for the disease and no standard treatment methods. The effects of hormone, Conventional Chinese medicine and other treatments are uncertain, with long treatment duration and notable side effects. Surgery is the preferred treatment, but the recurrence rate after conventional surgery is very high, which may be related to depression of the nipple. This study aimed to evaluate the efficacy of a novel corrective procedure in patients with cellular mastitis and depressed nipples.MethodsPatients with PCM who received surgical treatment in the Third Medical Center of PLA General Hospital from January 1996 to January 2018 were retrospectively analyzed. According to the presence or absence of nipple depression before surgery, the patients were divided into the nipple depression group and the non-nipple depression group. In the nipple depression group, patients were subdivided into a novel corrective surgery group (“one” suture or half pocket suture) and a conventional corrective surgery group (oil yarn traction valgus correction of nipple depression). Demographic, clinical, therapeutic, and postoperative relapse data were collected and analyzed.ResultsCompared with the patients in the non-nipple depression group, patients in the nipple depression group had a significantly higher recurrence risk after surgery (HR = 2.129 95% CI: 1.110–4.083, p = 0.023). Patients who underwent novel corrective surgery had a significantly lower recurrence risk than those who underwent conventional corrective surgery (HR = 0.363 95% CI: 0.150–0.880, p = 0.025). In addition, the novel corrective surgery significantly reduced the postoperative recurrence risk (HR = 0.088 95% CI: 0.009–0.886, p = 0.037).ConclusionHow to correct nipple depression is a critical factor for postoperative recurrence of PCM, and this novel corrective surgery for nipple depression can effectively reduce the postoperative recurrence rate in patients with nipple depression.

IntroductionPopliteal cysts are secondary to degenerative changes in the knee joint. After total knee arthroplasty (TKA), 56.7% of patients with popliteal cysts at 4.9 years follow-up remained symptomatic in the popliteal area. However, the result of simultaneous arthroscopic cystectomy and unicompartmental knee arthroplasty (UKA) was uncertain.Case presentationA 57-year-old man was admitted to our hospital with severe pain and swelling in his left knee and the popliteal area. He was diagnosed with severe medial unicompartmental knee osteoarthritis (KOA) with a symptomatic popliteal cyst. Subsequently, arthroscopic cystectomy and unicompartmental knee arthroplasty (UKA) were performed simultaneously. A month after the operation, he returned to his normal life. There was no progression in the lateral compartment of the left knee and no recurrence of the popliteal cyst at the 1-year follow-up.ConclusionFor KOA patients with a popliteal cyst seeking UKA, simultaneous arthroscopic cystectomy and UKA are feasible with great success if managed appropriately.

Abstract Targeting CD96 that originates in immune cells has shown potential for cancer therapy. However, the role of intrinsic CD96 in solid tumor cells remains unknown. Here, it is found that CD96 is frequently expressed in tumor cells from clinical breast cancer samples and is correlated with poor long‐term prognosis in these patients. The CD96+ cancer cell subpopulations exhibit features of both breast cancer stem cells and chemoresistance. In vivo inhibition of cancer cell‐intrinsic CD96 enhances the chemotherapeutic response in a patient‐derived tumor xenograft model. Mechanistically, CD96 enhances mitochondrial fatty acid β‐oxidation via the CD155‐CD96‐Src‐Stat3‐Opa1 pathway, which subsequently promotes chemoresistance in breast cancer stem cells. A previously unknown role is identified for tumor cell‐intrinsic CD96 and an attractive target in improving the chemotherapeutic response.

Balancing peptidoglycan (PG) synthesis and degradation with precision is essential for bacterial growth, yet our comprehension of this intricate process remains limited. The NlpI-Prc proteolytic complex plays a crucial but poorly understood role in the regulation of multiple enzymes involved in PG metabolism. In this paper, through fluorescent D-amino acid 7-hydroxycoumarincarbonylamino-D-alanine (HADA) labeling and immunolabeling assays, we have demonstrated that the NlpI-Prc complex regulates the activity of PG transpeptidases and subcellular localization of PBP3 under certain growth conditions. PBP7 (a PG hydrolase) and MltD (a lytic transglycosylase) were confirmed to be negatively regulated by the NlpI-Prc complex by an in vivo degradation assay. The endopeptidases, MepS, MepM, and MepH, have consistently been demonstrated as redundantly essential “space makers” for nascent PG insertion. However, we observed that the absence of NlpI-Prc complex can alleviate the lethality of the mepS mepM mepH mutant. A function of PG lytic transglycosylases MltA and MltD as “space makers” was proposed through multiple gene deletions. These findings unveil novel roles for NlpI-Prc in the regulation of both PG synthesis and degradation, shedding light on the previously undiscovered function of lytic transglycosylases as “space makers” in PG expansion.

Territorial ecological restoration (TER) is a critical step for promoting the development of an ecological civilization, as well as a significant strategic task relating to national ecological security and the well-being of a population. However, calculating the ecological restoration potential (ERP) is a key challenge in TER. Using Zhaoping County as an example, this study calculated the ecological restoration natural potential (ERNP), including the vegetation coverage potential, water conservation potential, windbreak and sand fixation potential, and biodiversity potential, and proposed an ERP calculation method based on the correction of ERNP with an ecological security pattern (ESP) and social support (SS). The findings revealed several key points. First, using the similarity habitat method to calculate ERNP highlighted significant disparities in the vegetation coverage, water conservation, windbreak and sand fixation, and biodiversity across Zhaoping County. These variations were contrary to regional ecological service functions. Second, overall, the ESP levels in Zhaoping County were high, accounting for about 60.42% of its total area being classified as high or relatively high level, with the towns exhibiting strong SS abilities primarily located in the northern region. Third, the ERP results which are between 0 and 1 indicated that areas with higher potential were mainly found in the west and northeast of Zhaoping, while lower potential areas were concentrated in the northwest and south; of them, the ERP index value in most regions is between 0.2 and 0.3, accounting for about 43.97% of the area. Finally, suggestions for the TER project layout and measures to enhance the ERP were proposed based on these ERP calculations. This study offers new insights into ERP strategies while providing guidance for identifying critical areas requiring restoration.

BackgroundTo investigate the occurrence of catheter malposition in breast cancer patients undergoing Totally Implantable Venous Access Port (TIVAP) implantation and analyze the effect of TIVAP implantation site on the incidence of catheter malposition.MethodsClinical data of Breast cancer patients underwent TIVAP implantation in our department from 2017 to 2021 was collected by reviewing the electronic medical records. The catheter malposition rate, location and management of malposed catheters in TIVAP implantation were analyzed. We divided the patients into the left internal jugular vein (IJV) group and the right IJV group according to the site of TIVAP implantation and compared the difference in the catheter malposition incidence between the two groups. In addition, we counted the catheter malposition rate of TIVAP implantion via the left and right IJV in right breast cancer patients to analyze the effect of tumor status on the side of TIVAP implantation on the catheter malposition rate.ResultsA total of 1,510 catheters were implanted in 1,504 patients, and 16 (1.06%) had catheter malposition. The catheter malposition rate was 4.96% (7/141) for TIVAP implanted via the left IJV and 0.66% (9/1,369) for right IJV, with a statistically significant difference (χ2 = 18.699, P

Gansu province will fulfill the carbon reduction target under the national carbon neutrality strategy. As a developing province in China, Gansu will have to trade off carbon reduction targets and economic development. This study adopts a computable general equilibrium model to simulate the carbon reduction pathway and estimate the possible impacts on the economy, output and environment under a carbon-neutral target. Our results show carbon emission will peak around 2033 in the baseline scenario and decline slowly after the peak. While carbon emissions will peak around 2023 in the carbon neutral scenario and decline very fast from 154 million tons in 2023 to 40 million ton in 2060. The economy will continue to increase from 734 billion CNY in 2017–3375 billion CNY in 2050 under a carbon reduction target, which means the carbon neutral target will have very limited economic impacts by 2060. At the sector level, economic outputs vary among different sectors. The output will increase significantly, such as power generation 14%, water supply 8% and nonmental 4%. Some other sectors will decrease quickly, paper 15% and textile industry 7%. Carbon reduction will also contribute to air pollutants reduction, which is a benefit to air quality. Carbon neutral targets will bring more opportunities in Gansu due to green energy potential without economic burden. Proper carbon mitigation policy would avoid the adverse impact but bring more potential to the economy in Gansu.

Land use change detection (LUCD) is a critical technology with applications in various fields, including forest disturbance, cropland changes, and urban expansion. However, the current review articles on LUCD tend to be limited in scope, rendering a comprehensive review challenging due to the vast number of publications. This paper systematically reviewed 3512 articles retrieved from the Web of Science Core database between 1985 and 2022, utilizing a combination of bibliometric analysis and machine learning methods with LUCD as the main focus. The results indicated an exponential increase in the number of LUCD studies, indicating continued growth in this research field. Commonly used methods include classification-based, threshold-based, model-based, and deep learning-based change detection, with research themes encompassing forest logging and vegetation succession, urban landscape dynamics, and biodiversity conservation and management. To build an intelligent change detection system, researchers need to develop a flexible framework that integrates data preprocessing, feature extraction, land use type interpretation, and accuracy evaluation, given the continuous evolution and application of remote sensing data, deep learning, big data, and artificial intelligence.

Soil organic matter (SOM) is an important component of soil and plays an important role in improving the soil’s physical and chemical properties. Ascertaining the spatial distribution of soil organic matter and its main controlling factors in the context of provincial scale farming is of important guiding significance for soil carbon sequestration, emission reduction and sustainable utilization. Using 257 soil profiles from the second soil survey in Shandong Province, GIS, we applied geostatistical methods to study the spatial distribution characteristics of SOM in topsoil. In addition, correlation and regression analyses were used to explore the main controlling factors over the spatial variation of SOM. The results showed that the mean amount of SOM in Shandong province ranged from 1.20–74.90 g·kg−1, with a coefficient of variation of 73.52%, which is a medium level of variation. The distribution of SOM in the study area was patchy, with higher levels of organic matter in the central, eastern, and northern parts, and lower levels of organic matter in the south-west. The comprehensive explanatory ability of all factors reached 52.30%. Soil type and parent material were the main controlling factors for the spatial variability of SOM in the Shandong Province, followed by soil texture and land use type, with topography and climatic factors having relatively little influence.

Abstract Background GAS5 contains a hormone response element that can induce cell apoptosis in breast cancer. It is known that cell apoptosis and hormone response play crucial roles in polycystic ovary syndrome (PCOS), indicating the potential involvement of GAS5 in PCOS. This study was performed to investigate the potential involvement of GAS5 and IL-6 (a critical player in PCOS) in PCOS. Methods Research subjects of this study included 60 PCOS patients and 60 healthy controls. The expression levels of GAS5 and IL-6 in plasma of both patients and controls were measured by qPCR and ELISA, respectively. Cell transfections were performed to analyze the interaction between GAS5 and IL-6. Cell apoptosis was analyzed by cell apoptosis assay. Results GAS5 was upregulated in plasma of PCOS patients. The expression levels of GAS5 were positively correlated with the expression levels of IL-6. Altered expression levels of GAS5 and IL-6 distinguished PCOS patients from healthy controls. In cells of a granulosa-like tumor cell line (KGN), overexpression of GAS5 led to upregulated IL-6, while silencing of GAS5 played an opposite role. Cell apoptosis analysis showed that overexpression of GAS5 significantly decreased apoptosis rate of KGN cells. Silencing of GAS5 increased the rate of KGN cell apoptosis. Conclusions GAS5 is upregulated in PCOS and regulates cell apoptosis and the expression of IL-6.

Insertion of new material into the Escherichia coli peptidoglycan (PG) sacculus between the cytoplasmic membrane and the outer membrane requires a well-organized balance between synthetic and hydrolytic activities to maintain cell shape and avoid lysis. Since most bacteria carry multiple enzymes carrying the same type of PG hydrolytic activity, we know little about the specific function of given enzymes. Here we show that the DD-carboxy/endopeptidase PBP4 localizes in a PBP1A/LpoA and FtsEX dependent fashion at midcell during septal PG synthesis. Midcell localization of PBP4 requires its non-catalytic domain 3 of unknown function, but not the activity of PBP4 or FtsE. Microscale thermophoresis with isolated proteins shows that PBP4 interacts with NlpI and the FtsEX-interacting protein EnvC, an activator of amidases AmiA and AmiB, which are needed to generate denuded glycan strands to recruit the initiator of septal PG synthesis, FtsN. The domain 3 of PBP4 is needed for the interaction with NlpI and EnvC, but not PBP1A or LpoA. In vivo crosslinking experiments confirm the interaction of PBP4 with PBP1A and LpoA. We propose that the interaction of PBP4 with EnvC, whilst not absolutely necessary for mid-cell recruitment of either protein, coordinates the activities of PBP4 and the amidases, which affects the formation of denuded glycan strands that attract FtsN. Consistent with this model, we found that the divisome assembly at midcell was premature in cells lacking PBP4, illustrating how the complexity of interactions affect the timing of cell division initiation.

The Qinghai– Tibet Plateau (QTP), which embodies the largest area of permafrost at mid–low altitudes of the world, has been experiencing rapid permafrost degradation and changes in freeze–thaw processes for the past decades. However, the responses and potential feedbacks of the methane flux from peatlands on the QTP to changing freeze–thaw cycles (FTCs) remain unknown. In this study, we collected peat soils from the Zoîgé peatlands, the largest peatland complex on the QTP, to examine methane emissions under simulated diurnal FTC scenarios. In incubation experiments of 15 days, two freeze–thaw temperature ranges of −5 to 4°C (mild) and −15 to 4°C (intense) were applied to two sets of peat soil samples, and each of them was characterized by 100% or 80% maximum water holding capacity (MWHC). The results showed that the peak of methane emission from the peat soil occurred after the first freeze–thaw cycle (FTC1), with the highest reaching a value of 0.103 mg kg soil−1·h−1. Generally, the cumulative methane emissions were elevated by FTCs, and relative higher rates of methane emissions were found for the 2nd FTC to the 15th FTC, compared with those from low-altitude peatlands. Methane emissions were significantly correlated to the export of dissolved organic carbon (DOC) and the activities of β-D-cellobiosidase and phenol oxidase in various freeze–thaw conditions. This study highlights the importance of FTCs in stimulating methane emissions and implies that methane emissions during FTCs from high-altitude peatlands would increase under a warmer climate in the future.

In recent years, the infrared electrochromic devices based on acid doped polyaniline films have achieved much progress, which has not been summarized before. This is important to accelerate the development of this field. In this paper, we will briefly review some representing work about the infrared electrochromic properties of acid doped polyaniline films, which were reported in the last 5 years.

Biomass energy is the most acknowledged renewable resource due to its universality, richness, and renewability. This study utilized a Portulaca oleracea L. plant as a natural colorant for wool fabric dyeing with a high color yield at optimum extraction and dyeing conditions. To evaluate the dyeing mechanism and feasibility of the extracted dyes, we analyzed and characterized the molecular structure and nano-level particle size. The dyeing kinetics and the morphology of dyed fabrics were integratedly explored; the adsorption process of wool fabric on natural colorant molecules was increasingly in line with the pseudo-second-order kinetic adsorption model. Further, the dyeing effects of wool fabrics were compared to that of Musa basjoo mordant and synthetic dyes to confirm the superior color depth (K/S value 23.53), biological function as anti-ultraviolet (UPF value 253.47), and anti-bacterial activity (antibacterial rate of Staphylococcus aureus/Escherichia coli was 71.3%/37%). Our findings provide a feasible scheme for providing deep color and biological activity to wool fabrics. This has broad application prospects in the field of eco-friendly textile materials.

As a sensitive, observable, and comprehensive indicator of climate change, plant phenology has become a vital topic of global change. Studies about plant phenology and its responses to climate change in natural ecosystems have drawn attention to the effects of human activities on phenology in/around urban regions. The key factors and mechanisms of phenological and human factors in the process of urbanization are still unclear. In this study, we analyzed variations in xylophyta phenology in densely populated cities during the fast urbanization period of China (from 1963 to 1988). We assessed the length of the growing season affected by the temperature and precipitation. Temperature increased the length of the growing season in most regions, while precipitation had the opposite effect. Moreover, the plant-growing season is more sensitive to preseason climate factors than to annual average climate factors. The increased population reduced the length of the growing season, while the growing GDP increased the length of the growing season in most regions (8 out of 13). By analyzing the impact of the industry ratio, we found that the correlation between the urban management of emerging cities (e.g., Chongqing, Zhejiang, and Guizhou) and the growing season is more significant, and the impact is substantial. In contrast, urban management in most areas with vigorously developed heavy industry (e.g., Heilongjiang, Liaoning, and Beijing) has a weak and insignificant effect on plant phenology. These results indicate that different urban development patterns can influence urban plant phenology. Our results provide some support and new thoughts for future research on urban plant phenology.

BackgroundBreast cancer (BC) is the most common tumor to develop cutaneous metastases. Most BCs with cutaneous metastasis are human epidermal growth factor receptor 2 (HER2)-positive subtypes. Although the molecular mechanisms of breast cancer metastasis to different sites and the corresponding treatment methods are areas of in-depth research, there are few studies on cutaneous metastasis.Case PresentationFive HER2-positive BC patients with extensive cutaneous metastases were treated with a regimen containing pyrotinib, a novel small-molecule tyrosine kinase inhibitor that irreversibly blocks epidermal growth factor receptor (EGFR), HER2, and human epidermal growth factor receptor 4 (HER4), then their cutaneous metastases quickly resolved at an astonishing speed and their condition was well controlled during the follow-up period.ConclusionsThis case series reports the significant therapeutic effect of pyrotinib on cutaneous metastases of HER2-positive BC for the first time. Based on this, we recommend that pyrotinib can be used as a supplement to trastuzumab for HER2-positive BC patients with cutaneous metastases. In addition, we should consider that the pan-inhibitory effect of pyrotinib on EGFR, HER2, and HER4 may provide a dual therapeutic effect against HER2 and mucin 1.

Abstract Carcinoma‐associated fibroblasts (CAFs) consist of heterogeneous subpopulations that play a critical role in the dynamics of the tumor microenvironment. The extracellular signals of CAFs have been attributed to the extracellular matrix, cytokines, cell surface checkpoints, and exosomes. In the present study, it is demonstrated that the CD10 transmembrane hydrolase expressed on a subset of CAFs supports tumor stemness and induces chemoresistance. Mechanistically, CD10 degenerates an antitumoral peptide termed osteogenic growth peptide (OGP). OGP restrains the expression of rate‐limiting desaturase SCD1 and inhibits lipid desaturation, which is required for cancer stem cells (CSCs). Targeting CD10 significantly improves the efficacy of chemotherapy in vivo. Clinically, CD10‐OGP signals are associated with the response to neoadjuvant chemotherapy in patients with breast cancer. The collective data suggest that a nexus between the niche and lipid metabolism in CSCs is a promising therapeutic target for breast cancer.