Cross-species single-cell analysis uncovers the immunopathological mechanisms associated with IgA nephropathy progression.

IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes. IgAN macrophages expressed high levels of CXCR4, PDGFB, triggering receptor expressed on myeloid cells 2, TNF, and C3, and the trajectory analysis suggested that these cells derived from the differentiation of infiltrating blood monocytes. Additionally, protein profiling of 21 progression and 28 nonprogression IgAN samples revealed that proteins CXCL12, C3, mannose receptor C-type 1, and CD163 were negatively correlated with estimated glomerular filtration rate (eGFR) value and poor prognosis (30% eGFR as composite end point). Last, a functional experiment revealed that specific blockade of the Cxcl12/Cxcr4 pathway substantially attenuated the glomerulus and tubule inflammatory injury, fibrosis, and renal function decline in the mouse IgAN model. This study provides insights into IgAN progression and may aid in the refinement of IgAN diagnosis and the optimization of treatment strategies.

Transcription factor EHF drives cholangiocarcinoma development through transcriptional activation of glioma-associated oncogene homolog 1 and chemokine CCL2.

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation-specific homologous factor (EHF), a member of the E26 transformation-specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma-associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor-associated macrophages (TAMs) through the C-C motif chemokine 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co-expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF-mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2-TAMs to inhibit EHF-driven CCA development.

Functional characterization of geranyl/farnesyl diphosphate synthase in Wurfbainia villosa and Wurfbainia longiligularis.

Wurfbainia villosa and Wurfbainia longiligularis are the two primary plant sources of Fructus Amomi, a traditional Chinese medicine. Both plants are rich in volatile terpenoids, including monoterpenes and sesquiterpenes, which are the primary medicinal components of Fructus Amomi. The trans-isopentenyl diphosphate synthase (TIDS) gene family plays a key part in determining terpenoid diversity and accumulation. However, the TIDS gene family have not been identified in W. villosa and W. longiligularis. This study identified thirteen TIDS genes in W. villosa and eleven TIDS genes in W. longiligularis, which may have expanded through segmental replication events. Based on phylogenetic analysis and expression levels, eight candidate WvTIDSs and five WlTIDSs were selected for cloning. Functional characterization in vitro demonstrated that four homologous geranyl diphosphate synthases (GPPSs) (WvGPPS1, WvGPPS2, WlGPPS1, WlGPPS2) and two geranylgeranyl diphosphate synthases (GGPPSs) (WvGGPPS and WlGGPPS) were responsible for catalyzing the biosynthesis of geranyl diphosphate (GPP), whereas two farnesyl diphosphate synthases (FPPSs) (WvFPPS and WlFPPS) catalysed the biosynthesis of the farnesyl diphosphate (FPP). A comparison of six proteins with identified GPPS functions showed that WvGGPPS and WlGGPPS exhibited the highest activity levels. These findings indicate that homologous GPPS and GGPPS together promote the biosynthesis of GPP in W. villosa and W. longiligularis, thus providing sufficient precursors for the synthesis of monoterpenes and providing key genetic elements for Fructus Amomi variety improvement and molecular breeding.

The role of pre-onset hair hormone in predicting the prognosis of patients with severe pneumonia and acute COVID-19 outbreak.

Numerous research works have investigated the potential impact of endocrine hormones on the severity of COVID-19-related pneumonia in individuals. However, there are few studies on the effect of pre-onset neuroendocrine hormones on the prognosis of COVID-19 patients. This study looked into the prognostic value of pre-onset hair hormone levels in COVID-19 infected individuals. This study included 27 patients with COVID-19 and collected patient information and laboratory indicators. The hormone levels in hair were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Within 28 days, 63 % of the patients in this study passed away. With 28-day mortality as the outcome index, urea nitrogen, CURB-65 score and pneumonia severity score (PSI) of 2 groups were statistically significant (P < 0.05). Among all hormone levels detected in hair, only progesterone level was substantially correlated negatively with COVID-19 patients' 28-day mortality(P < 0.05). The level of progesterone in hair was substantially adversely connected with the death rate at 28 days of COVID-19 patients, according to correlation and logistic regression analysis(P < 0.05). Among patients with COVID-19 pneumonia, hair progesterone levels were strongly associated with 28-day mortality, which emphasizes hair progesterone's importance as a prognostic factor.

Pathophysiology and transcriptomic responses of Pinus armandii defenses to ophiostomatoid fungi.

Pinus armandii is an ecologically and economically important evergreen tree species native to western China. Dendroctonus armandi and pathogenic ophiostomatoid fungi pose substantial threats to P. armandii. With the interplay between species, the defense mechanisms of P. armandii have evolved to withstand external biotic stressors. However, the interactions between P. armandii and pathogenic ophiostomatoid fungal species/strains remain poorly understood. We aimed to analyze the pathophysiological and molecular changes in P. armandii following artificial inoculation with four ophiostomatoid species (Graphilbum parakesiyea, Leptographium qinlingense, Ophiostoma shennongense, and Ophiostoma sp. 1). The study revealed that L. qinlingense produced the longest necrotic lesions, and G. parakesiyea produced the shortest. All strains induced monoterpenoid release, and monoterpene levels of P. armandii were positively correlated with fungal virulence (R2 = 0.93, P < 0.01). Co-inoculation of two dominant highly (L. qinlingense) and weakly virulent (O. shennongense) pathogens reduced the pathogenicity of the highly virulent fungi. Transcriptomic analysis of P. armandii (LQ: L. qinlingense treatments, QS: co-inoculation treatments, and OS: O. shennongense treatments) showed that the expression pattern of differentially expressed genes (DEGs) between QS and OS was similar, but different from that of LQ. The DEGs (LQ vs. QS) involved in flavonoid biosynthesis and phenylpropanoid biosynthesis were downregulated. Notably, compared with LQ, QS significantly decreased the expression of host defense-related genes. This study provides a valuable theoretical basis for managing infestations of D. armandi and associated ophiostomatoid fungi.

Elabela mitigates the early stage of inflammation in sepsis by inhibiting pyroptosis.

OBJECTIVES: This study aims to investigate the potential therapeutic role of Elabela (ELA) in mitigating the sepsis-induced inflammatory storm, a phenomenon commonly associated with multiple organ dysfunction syndrome (MODS) and increased mortality. Our findings show the pathogenesis of sepsis, identifying ELA as a promising therapeutic target. METHODS: We conducted a comprehensive analysis of electronic medical records and blood samples from septic patients to assess the incidence of severe organ complication and characterize the inflammatory response. Subsequently, we measured the expression levels of ELA and various inflammatory factors in serum, and performed correlation analysis to explore the relationship between them, aiming to identify the cells and inflammatory pathways targeted by ELA. Furthermore, animal and cellular experiments were conducted to investigate the molecular mechanism underlying the therapeutic effect of ELA. RESULTS: Our findings revealed a higher prevalence of severe organ complications among septic patients, contributing to adverse prognoses and increased mortality. Notably, these patients exhibited significantly elevated levels of inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in their sera, indicating a robust inflammatory response. Correlation analysis revealed a negative correlation between ELA and IL-1ß in septic patients. Through animal and cellular experiments, we demonstrated that ELA inhibits the cleavage of caspase-1 and gasdermin D (GSDMD), thereby attenuating pyroptosis and the inflammatory response. CONCLUSIONS: ELA is a promising therapeutic agent for mitigating the deleterious effects of sepsis. Its ability to inhibit macrophage pyroptosis and suppress the inflammatory response offers a novel approach.

Value of third-generation of VNCa dual-energy CT for differentiating diffuse marrow infiltration of multiple myeloma from red bone marrow.

This study aims to investigate the ability of bone marrow imaging using third-generation dual-energy computed tomography (CT) virtual noncalcium (VNCa) to differentiate between multiple myeloma (MM) with diffuse bone marrow infiltration and red bone marrow (RBM). Bone marrow aspiration or follow-up results were used as reference. We retrospectively reviewed 188 regions of interests (ROIs) from 21 patients with confirmed MM and diffuse bone marrow infiltrations who underwent VNCa bone marrow imaging between May 2019 and September 2022. At the same time, we obtained 98 ROIs from 11 subjects with RBM for comparative study, and 189 ROIs from 20 subjects with normal yellow bone marrow for the control group. The ROIs were delineated by 2 radiologists independently, the interobservers reproducibility was evaluated by interclass correlation coefficients. The correlation with MRI grade results was analyzed by Spearman correlation coefficient. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal threshold for differentiating between these groups and to assess diagnostic performance. There were statistically significant differences in VNCa CT values of bone marrow among the MM, RBM, and control groups (all P < .001), with values decreasing sequentially. A strong positive rank correlation was observed between normal bone marrow, subgroup MM with moderately and severe bone marrow infiltration divided by MRI and their corresponding CT values (ρ = 0.897, 95%CI: 0.822 to 0.942, P < .001). When the CT value of VNCa bone marrow was 7.15 HU, the area under the curve (AUC) value for differentiating RBM and MM was 0.723, with a sensitivity of 50.5% and a specificity of 89.8%. When distinguishing severe bone marrow infiltration of MM from RBM, the AUC value was 0.80 with a sensitivity 70.9% and a specificity 78.9%. The AUC values for MM, RBM, and the combined group compared to the control group were all >0.99, with all diagnostic sensitivity and specificity exceeding 95%. VNCa bone marrow imaging using third-generation dual-energy CT accurately differentiates MM lesions from normal bone marrow or RBM. It demonstrates superior diagnostic performance in distinguishing RBM from MM with diffuse bone marrow infiltration.

m6A-methylated Lonp1 drives mitochondrial proteostasis stress to induce testicular pyroptosis upon environmental cadmium exposure.

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.

A new insight on evaluation of the fertility and pregnancy outcome in patients with primary Sjögren syndrome: a propensity score matched study in multi-IVF centers.

BACKGROUND: Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it's currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it's unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients. OBJECTIVE: This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers. METHODS: We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching. RESULTS: Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P < 0.001; 6.0 vs. 10.0, P < 0.001, respectively). The pSS group performed significant reductions in numbers of large follicles, oocytes retrieved and MII oocytes. Additionally, pSS patients exhibited obviously deteriorate rates of oocyte maturation, 2PN cleavage, D3 good-quality embryo, and blastocyst formation compared to comparison. As for clinical pregnancy, notable decrease was found in implantation rate (37.9% vs. 54.9%, P = 0.022). The cumulative live birth rate (CLBR) following every embryo-transfer procedure was distinctly lower in the pSS group, and the conservative and optimal CLBRs following every complete cycle procedure were also significantly reduced in the pSS group. Lastly, the gestational weeks of the newborns in pSS group were distinctly early vs comparison. CONCLUSION: Patients with pSS exhibit worse conditions in terms of female fertility and clinical pregnancy, notably accompanied with deteriorate oocyte and embryo development. Individualized fertility evaluation and early fertility guidance are essential for these special patients.

The impact of work environment on caring behavior among Chinese hospice nurses: the chain mediating effect of psychological capital and empathy.

Introduction: The caring behavior of hospice nurses toward patients positively impacts their professional careers and significantly improves the quality of hospice services. A positive and supportive work environment may protect nurses against negative emotions that may affect the humanistic care they provide, and their job satisfaction. This study aimed to explore the impact of the nursing work environment on caring behavior. We also investigated the chain mediating effect of psychological capital and empathy on this relationship among Chinese hospice nurses. Methods: The Practice Environment Scale (PES), the Psychological Capital Questionnaire (PCQ), the Empathy Ability Scale for Hospice Nurses, and the Caring Behaviors Inventory (CBI) were used to survey 393 Chinese hospice nurses. SPSS 27.0 and Mplus 8.0 were used for statistical processing to analyze the mediating effects. Results: The nursing work environment positively predicted caring behavior. Furthermore, it was found that psychological capital and empathy jointly mediate the relationship between the nursing work environment and caring behavior. Conclusion: This study reveals how the nursing work environment affects the caring behavior of hospice nurses. Hospital managers need to provide hospice nurses with a favorable working environment from the perspective of positive psychology, continuously monitor their psychological state, improve their caring behavior, and provide references for developing intervention plans to promote the caring behavior of hospice nurses in the future.

Retrospective analysis of urethral anastomosis with ancillary maneuvers and intraoperative biaxial defect measurements to achieve a tension free guidance system for redo PFUDD treatment.

OBJECTIVES: Redo surgery for pelvic fracture urethral distraction defects (PFUDDs) is still a challenge. the long urethral defect makes it difficult while the high tension increase the recurrence rate. Although certain ancillary maneuvers can relieve tension, there is no consensus or guidelines for the prediction/planning of the selection. In this study, we present our experience with developing an intraoperative guidance system to achieve tension-free urethral anastomosis. PATIENTS AND METHODS: A total of 91 recurrent PFUDD patients managed at our center between 2020 and 2022 were retrospectively analyzed. The patients underwent scar removing and urethral anastomosis. For the long defect and high-tension cases, 6 kinds of tension-relieving maneuvers were used respectively during the process of urethral anastomosis. Preoperative assessment of the urethrogram was done before surgery, while biaxial (vertical and horizontal) defect measurements were performed intraoperatively. The patients were followed-up for 12 months (8.9 ± 4.2), furthermore, recurrence and complications were analyzed. RESULTS: The overall success rate was 86.81%. The mean defect in urethrogram was 2.9 ± 1.1 cm. 27 simple anastomosis was performed when the vertical plus horizontal defect was less than 2 cm with 11.11% recurrence. 24 cavernous septum splittings were performed when the horizontal defect was greater than 2 cm with 8.33% recurrence. 21 inferior pubectomies were performed when the horizontal defect was greater than 3 cm with 19.05% recurrence. 15 ancillary distal urethra manipulations (fully distal urethral mobilization, urethral suspension and corpus cavernosa folding) were performed when the vertical defect was 3 to 4 cm with 13.33 recurrence. 4 reroutings were performed when the vertical defect was greater than 4 cm with 25.00% recurrence. CONCLUSIONS: Ancillary maneuvers are effective for reducing tension in redo urethral anastomosis. Measurement of divergent vertical and horizontal urethral defects could guide the selection of ancillary maneuvers. Combined tension-relieving maneuvers is recommended according to the defect direction and length to achieve a tension-free anastomosis.

Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion.

Paradoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance to tumor cells, impaired transport of T cells, and the formation of an immunosuppressive tumor microenvironment. A population of distinct immature myeloid cells, myeloid-derived suppressor cells (MDSCs), mediate immune escape primarily by exerting immunosuppressive effects and participating in the constitution of an immunosuppressive microtumor environment. Clinical trials have found that the levels of MDSCs in the peripheral blood of cancer patients are strongly correlated with tumor stage, metastasis and prognosis. Moreover, animal experiments have confirmed that elimination of MDSCs inhibits tumor growth and metastasis to some extent. Therefore, MDSCs may become the target of immunotherapy for many cancers, and eliminating MDSCs can help improve the response rate to cancer treatment and patient survival. However, a clear definition of MDSCs and the specific mechanism involved in immune escape are lacking. In this paper, we review the role of the MDSCs population in tumor development and the mechanisms involved in immune escape in different tumor contexts. In addition, we discuss the use of these cells as targets for tumor immunotherapy. This review not only contributes to a systematic and comprehensive understanding of the essential role of MDSCs in immune system reactions against tumors but also provides information to guide the development of cancer therapies targeting MDSCs.

Chemical derivatization strategies for enhancing the HPLC analytical performance of natural active triterpenoids.

Triterpenoids widely exist in nature, displaying a variety of pharmacological activities. Determining triterpenoids in different matrices, especially in biological samples holds great significance. High-performance liquid chromatography (HPLC) has become the predominant method for triterpenoids analysis due to its exceptional analytical performance. However, due to the structural similarities among botanical samples, achieving effective separation of each triterpenoid proves challenging, necessitating significant improvements in analytical methods. Additionally, triterpenoids are characterized by a lack of ultraviolet (UV) absorption groups and chromophores, along with low ionization efficiency in mass spectrometry. Consequently, routine HPLC analysis suffers from poor sensitivity. Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance. Considering the structural characteristics of triterpenoids, various derivatization reagents such as acid chlorides, rhodamines, isocyanates, sulfonic esters, and amines have been employed for the derivatization analysis of triterpenoids. This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids. Moreover, the limitations and challenges encountered in previous studies are discussed, and future research directions are proposed to develop more effective derivatization methods.

Impact of long-term mining activity on groundwater dynamics in a mining district in Xinjiang coal Mine Base, Northwest China: insight from geochemical fingerprint and machine learning.

Long-term coal mining could lead to a serious of geo-environmental problems. However, less comprehensive identification of factors controlling the groundwater dynamics were involved in previous studies. This study focused on 68 groundwater samples collected before and after mining activities, Self-Organizing Maps (SOM) combining with Principal Component Analysis (PCA) derived that the groundwater samples were classified into five clusters. Clusters 1-5 (C1-C5) represented the groundwater quality affected by different hydrochemical processes, mainly including mineral (carbonate and evaporite) dissolution and cation exchange, which were controlled by the hydrochemical environment at different stages of mining activities. Combining with the time-series data, the Extreme Gradient Boosting Decision Trees (XGBoost) derived that the mine water inflow (feature relative importance of 40.0%) and unit goaf area (feature relative importance of 29.2%) were dominant factors affecting the confined groundwater level, but had less or lagged impact on phreatic groundwater level. This was closely related to the height of the water flow fractured zone and hydraulic connection between aquifers. The results of this study on the coupled evolution of groundwater dynamics could enhance our understanding of the effects of mining on aquifer systems and contribute to the prevention of water hazards in the coalfields.

Reducing the contaminant dispersion and infection risks in the train cabins by adjusting the inlet turbulence intensity: A study based on turbulence simulation.

Existing studies on ventilation in closed spaces mainly considered the average inlet velocity and ignored the influence of inlet turbulent fluctuation. However, the variation in inlet turbulence intensity (TI) is considerable and significantly affects the dispersion of contaminants. This study conducts numerical simulations verified by experiments to investigate the effect of the inlet TI on train contaminants dispersion and analyze infection probability variation. Firstly, the unsteady Reynolds-averaged Navier-Stokes (URANS) method and improved delayed detached eddy simulation (IDDES) method are compared in simulating the internal airflow characteristics based on the on-site measurement. The results indicate that the latter dominates in capturing airflow pulsations more than the former, although the mean airflow results obtained from both methods agree well with experimental results. Furthermore, the IDDES method is employed to investigate the effect of the inlet TI on contaminant dispersion, and the infection risks are also assessed using the improved probability model. The results show that, with the increase of TI from 5 % to 30 %, the contaminant removal grows considerably, with the removal index rising from 0.23 to 1.86. The increased TI leads to the overall and local infection risks of occupants descending significantly, wherein the former decreases from 1.53 % to 0.88 % with a reduction rate of 42 %, and the latter drops from 3.30 % to 2.16 % with a mitigation rate of 35 %. The findings can serve as solid guidelines for numerical method selection in accurately capturing the indoor dynamic airflow distribution and for the ventilation parameters design regarding TI inside trains to mitigate the airborne infection risk.

Analysis of trajectory changes and predictive factors of sense of coherence in patients after colorectal cancer surgery.

OBJECTIVE: To investigate the trajectories and potential categories of changes in the sense of coherence (SOC) in patients after colorectal cancer surgery and to analyze predictive factors. METHODS: From January to July 2023, 175 patients with colorectal cancer treated at a tertiary Grade A oncology hospital in Jiangsu Province were selected as the study subjects. Prior to surgery, SOC-13 scale, Patient-Generated Subjective Global Assessment (PG-SGA), Brief Illness Perception Questionnaire (BIPQ), and Social Support Rating Scale (SSRS) were used to survey the patients. SOC levels were measured multiple times at 1 week, 1 month, and 3 months post-surgery. Growth Mixture Modeling (GMM) was applied to fit the trajectory changes of SOC in patients after colorectal cancer surgery. Multinomial logistic regression was used to analyze the predictive factors of SOC trajectory changes. RESULTS: The SOC scores of patients at points T1-T4 were (65.27 ± 9.20), (63.65 ± 10.41), (63.85 ± 11.84), and (61.56 ± 12.65), respectively. Multinomial logistic regression results indicated that gender, employment status, disease stage, household monthly income, intestinal stoma, nutritional status, illness perception, and social support were predictors of SOC trajectory changes (P < 0.05). CONCLUSION: There is heterogeneity in the trajectory changes of SOC in patients after colorectal cancer surgery. Healthcare professionals should implement early precision interventions based on the patterns of changes and predictive factors in each trajectory category.

Radiation and male reproductive system: Damage and protection.

Male fertility has been declining in recent decades, and a growing body of research points to environmental and lifestyle factors as the cause. The widespread use of radiation technology may result in more people affected by male infertility, as it is well established that radiation can cause reproductive impairment in men. This article provides a review of radiation-induced damage to male reproduction, and the effects of damage mechanisms and pharmacotherapy. It is hoped that this review will contribute to the understanding of the effects of radiation on male reproduction, and provide information for research into drugs that can protect the reproductive health of males.

Cotton sphingosine kinase GhLCBK1 participates in fiber cell elongation by affecting sphingosine-1-phophate and auxin synthesis.

Sphingolipids serve as essential components of biomembrane and possess significant bioactive properties. Sphingosine-1-phophate (S1P) plays a key role in plant resistance to stress, but its specific impact on plant growth and development remains to be fully elucidated. Cotton fiber cells are an ideal material for investigating the growth and maturation of plant cells. In this study, we examined the content and composition of sphingosine (Sph) and S1P throughout the progression of fiber cell development. The content of S1P elevated gradually during fiber elongation but declined during the transition stage. Exogenous application of S1P promoted fiber elongation while using of FTY720 (an antagonist of S1P), and DMS (an inhibitor of LCBK) hindered fiber elongation. Cotton Long Chain Base Kinase 1 (GhLCBK1) was notably expressed during the fiber elongation stage, containing all conserved domains of LCBK protein and localized in the endoplasmic reticulum. Overexpression GhLCBK1 increased the S1P content and promoted fiber elongation while retarded secondary cell wall (SCW) deposition. Conversely, downregulation of GhLCBK1 reduced the S1P levels, and suppressed fiber elongation, and accelerated SCW deposition. Transcriptome analysis revealed that upregulating GhLCBK1 or applying S1P induced the expression of GhEXPANSIN and auxin related genes. Furthermore, the levels of IAA were elevated and reduced in the fibers when up-regulating or down-regulating GhLCBK1, respectively. Our investigation demonstrated that GhLCBK1 and its product S1P facilitated the elongation of fiber cells by affecting auxin biosynthesis. This study contributes novel insights into the intricate regulatory pathways involved in fiber cell elongation, identifying GhLCBK1 as a potential target gene and laying the groundwork for enhancing fiber quality via genetic manipulation.

Exploring novel indazole derivatives as ASK1 inhibitors: Design, synthesis, biological evaluation and docking studies.

Apoptosis signal regulated kinase 1 (ASK1, MAP3K5) is a member of the mitogen activated protein kinase (MAPK) signaling pathway, involved in cell survival, differentiation, stress response, and apoptosis. ASK1 kinase inhibition has become a promising strategy for the treatment of Non-alcoholic steatohepatitis (NASH) disease. A series of novel ASK1 inhibitors with indazole scaffolds were designed and synthesized, and their ASK1 kinase activities were evaluated. The System Structure Activity Relationship (SAR) study discovered a promising compound 33c, which has a strong inhibitory effect on ASK1. Noteworthy observations included a discernible reduction in lipid droplets within LO2 cells stained with Oil Red O, coupled with a decrease in LDL, CHO, and TG content within the NASH model cell group. Mechanistic inquiries revealed that compound 33c could inhibit the protein expression levels of the upregulated ASK1-p38/JNK signaling pathway in TNF-α treated HGC-27 cells and regulate apoptotic proteins. In summary, these findings suggest that compound 33c may be valuable for further research as a potential candidate compound against NASH.

Factors promoting and hindering resilience in youth with inflammatory bowel disease: A descriptive qualitative study.

AIM: To explore factors promoting and hindering resilience in youth with inflammatory bowel disease (IBD) based on Kumpfer's resilience framework. DESIGN: A descriptive qualitative study design with an interpretative approach was used. METHODS: Participants consisted of 10 youths with IBD from a tertiary hospital in Beijing (China) recruited using the purposive sampling method. Data were collected by semi-structured interviews from December 2020 to March 2021. The directed content analysis was performed for data analysis. RESULTS: Both promoting factors and hindering factors could be divided into personal factors and environmental factors. Thirteen themes were identified. The promoting factors included acceptance of illness, strict self-management, previous treatment experience, life goals, family support, medical support and peer encouragement. Stigma, lack of communication, negative cognition, societal incomprehension, economic pressure and academic and employment pressure were hindering factors. CONCLUSION: Health care professionals need to develop greater awareness of factors, stemming from both the individual and the outside world, that hinder or promote resilience in order to aid young patients with IBD. Building targeted nursing measures to excavate the internal positive quality of patients, provide external support and promote the development of resilience.