Saponin and Ribosome-Inactivating Protein Synergistically Trigger Lysosome-Dependent Apoptosis by Inhibiting Lysophagy: Potential to Become a New Antitumor Strategy.

The susceptibility of lysosomal membranes in tumor cells to cationic amphiphilic drugs (CADs) enables CADs to induce lysosomal membrane permeabilization (LMP) and trigger lysosome-dependent cell death (LDCD), suggesting a potential antitumor therapeutic approach. However, the existence of intrinsic lysosomal damage response mechanisms limits the display of the pharmacological activity of CADs. In this study, we report that low concentrations of QS-21, a saponin with cationic amphiphilicity extracted from Quillaja Saponaria tree, can induce LMP but has nontoxicity to tumor cells. QS-21 and MAP30, a type I ribosome-inactivating protein, synergistically induce apoptosis in tumor cells at low concentrations of both. Mechanistically, QS-21-induced LMP helps MAP30 escape from endosomes or lysosomes and subsequently enter the endoplasmic reticulum, where MAP30 downregulates the expression of autophagy-associated LC3 proteins, thereby inhibiting lysophagy. The inhibition of lysophagy results in the impaired clearance of damaged lysosomes, leading to the leakage of massive lysosomal contents such as cathepsins into the cytoplasm, ultimately triggering LDCD. In summary, our study showed that coadministration of QS-21 and MAP30 amplified the lysosomal disruption and can be a new synergistic LDCD-based antitumor therapy.

Fraxetin Targeting to Sortase A Decreases the Pathogenicity of Streptococcus agalactiae to Nile Tilapia.

Sortase A (SrtA) is responsible for anchoring surface proteins to the cell wall, and has been identified as a promising target developing anti-infective drugs of Gram-positive bacteria. The aim of the study was to identify inhibitors of Streptococcus agalactiae (S. agalactiae) SrtA from natural compounds to overcome the spread of antibiotic resistance in aquaculture. Here, we found that the MIC of fraxetin against S. agalactiae was higher than 256 µg/mL, indicating that fraxetin had no anti- S. agalactiae activity. But fraxetin could dose-dependently decrease the activity of SrtA in vitro at concentrations ranging between 4-32 µg/mL by a fluorescence resonance energy transfer (FRET) assay. Moreover, the inhibition of SrtA by fraxetin decreased the anchoring of surface proteins with the LPXTG motif to the cell wall by detecting the immunofluorescence change of serine-rich repeat protein 1 (Srr1) on the bacterial cell surface. The results of fibronectin binding and cell adhesion assays indicated that fraxetin could significantly decrease the adhesion ability of S. agalactiae in a dose-dependent manner. The results were further proven by immunofluorescence staining. Animal challenge results showed that treatment with fraxetin could reduce the mortality of tilapia infected with S. agalactiae to 46.67%, indicating that fraxetin could provide a significant amount of protection to tilapia by inactivating SrtA. Taken together, these findings provided a novel inhibitor of S. agalactiae SrtA and a promising candidate for treating S. agalactiae infections in aquaculture.

Beyond order-based nursing workload: A retrospective cohort study in intensive care units.

INTRODUCTION: In order to be positioned to address the increasing strain of burnout and worsening nurse shortage, a better understanding of factors that contribute to nursing workload is required. This study aims to examine the difference between order-based and clinically perceived nursing workloads and to quantify factors that contribute to a higher clinically perceived workload. DESIGN: A retrospective cohort study was used on an observational dataset. METHODS: We combined patient flow, nurse staffing and assignment, and workload intensity data and used multivariate linear regression to analyze how various shift, patient, and nurse-level factors, beyond order-based workload, affect nurses' clinically perceived workload. RESULTS: Among 53% of our samples, the clinically perceived workload is higher than the order-based workload. Factors associated with a higher clinically perceived workload include weekend or night shifts, shifts with a higher census, patients within the first 24 h of admission, and male patients. CONCLUSIONS: The order-based workload measures tended to underestimate nurses' clinically perceived workload. We identified and quantified factors that contribute to a higher clinically perceived workload, discussed the potential mechanisms as to how these factors affect the clinically perceived workload, and proposed targeted interventions to better manage nursing workload. CLINICAL RELEVANCE: By identifying factors associated with a high clinically perceived workload, the nurse manager can provide appropriate interventions to lighten nursing workload, which may further reduce the risk of nurse burnout and shortage.

Clinical Features and Surgical Outcomes of Spinal Hamartomas: surgical treatment of 8 patients.

OBJECTIVE: Rarely do spinal hamartomas receive attention in the literature, and the majority of previous studies consist of case reports. The purpose of this report, then, is to provide a more accurate diagnosis and treatment of spinal hamartomas by presenting the clinical and surgical outcomes of 8 cases. METHODS: The researchers conducted a retrospective analysis of the data for eight individuals with spinal hamartomas. The eight patients had undergone both preoperative and postoperative magnetic resonance imaging (MRI) and went through surgery. Radiological and pathological criteria were applied to diagnose the spinal hamartomas. The Modified McCormick classification system was used to evaluate neurological function in these patients. RESULTS: Among the eight patients, six were male and two were female, with an average age of 37.4 years. The typical duration of symptoms was 14.5 months. During surgery, all lesions were well-defined and located in the bone marrow. Gross total resection (GTR) was achieved in 6 cases, and the anatomical plane was clearly delineated, and subtotal resection (STR) was achieved in 2 cases. None of the patients took postoperative radiotherapy. 14.5 months was the average follow-up period, during this time, MRI did not observe the recurrence or regeneration of residual tumors. The McCormick grade was improved in seven patients and remained stable in one patient. CONCLUSIONS: Spinal hamartomas are benign, but they are clinically progressive lesions. Pathology is the basis of accurate diagnosis, and complete preoperative evaluation is crucial for providing suitable treatment and prognosis.

The effects of ambient temperature on road traffic injuries in Jinan city: a time-stratified case-crossover study based on distributed lag nonlinear model.

Objectives: The impact of climate change, especially extreme temperatures, on health outcomes has become a global public health concern. Most previous studies focused on the impact of disease incidence or mortality, whereas much less has been done on road traffic injuries (RTIs). This study aimed to explore the effects of ambient temperature, particularly extreme temperature, on road traffic deaths in Jinan city. Methods: Daily data on road traffic deaths and meteorological factors were collected among all residents in Jinan city during 2011-2020. We used a time-stratified case-crossover design with distributed lag nonlinear model to evaluate the association between daily mean temperature, especially extreme temperature and road traffic deaths, and its variation in different subgroups of transportation mode, adjusting for meteorological confounders. Results: A total of 9,794 road traffic deaths were collected in our study. The results showed that extreme temperatures were associated with increased risks of deaths from road traffic injuries and four main subtypes of transportation mode, including walking, Bicycle, Motorcycle and Motor vehicle (except motorcycles), with obviously lag effects. Meanwhile, the negative effects of extreme high temperatures were significantly higher than those of extreme low temperatures. Under low-temperature exposure, the highest cumulative lag effect of 1.355 (95% CI, 1.054, 1.742) for pedal cyclists when cumulated over lag 0 to 6 day, and those for pedestrians, motorcycles and motor vehicle occupants all persisted until 14 days, with ORs of 1.227 (95% CI, 1.102, 1.367), 1.453 (95% CI, 1.214, 1.740) and 1.202 (95% CI, 1.005, 1.438), respectively. Under high-temperature exposure, the highest cumulative lag effect of 3.106 (95% CI, 1.646, 5.861) for motorcycle occupants when cumulated over lag 0 to 12 day, and those for pedestrian, pedal cyclists, and motor vehicle accidents all peaked when persisted until 14 days, with OR values of 1.638 (95% CI, 1.281, 2.094), 2.603 (95% CI, 1.695, 3.997) and 1.603 (95% CI, 1.066, 2.411), respectively. Conclusion: This study provides evidence that ambient temperature is significantly associated with the risk of road traffic injuries accompanied by obvious lag effect, and the associations differ by the mode of transportation. Our findings help to promote a more comprehensive understanding of the relationship between temperature and road traffic injuries, which can be used to establish appropriate public health policies and targeted interventions.

Neurotoxic lesions of the anterior claustrum influence cued fear memory in rats.

Background: The claustrum (CLA), a subcortical area between the insular cortex and striatum, innervates almost all cortical regions of the mammalian brain. There is growing evidence that CLA participates in many brain functions, including memory, cognition, and stress response. It is proposed that dysfunction or malfunction of the CLA might be the pathology of some brain diseases, including stress-induced depression and anxiety. However, the role of the CLA in fear memory and anxiety disorders remains largely understudied. Methods: We evaluated the influences of neurotoxic lesions of the CLA using auditory-cued fear memory and anxiety-like behaviors in rats. Results: We found that lesions of anterior CLA (aCLA) but not posterior CLA (pCLA) before fear conditioning attenuated fear retrieval, facilitated extinction, and reduced freezing levels during the extinction retention test. Post-learning lesions of aCLA but not pCLA facilitated fear extinction and attenuated freezing behavior during the extinction retention test. Lesions of aCLA or pCLA did not affect anxiety-like behaviors evaluated by the open field test and elevated plus-maze test. Conclusion: These data suggested that aCLA but not pCLA was involved in fear memory and extinction. Future studies are needed to further investigate the anatomical and functional connections of aCLA subareas that are involved in fear conditioning, which will deepen our understanding of CLA functions.

CCR5 antagonist maraviroc alleviates doxorubicin-induced neuroinflammation and neurobehavioral deficiency by regulating NF-κB/NLRP3 signaling in a breast cancer mouse model.

The chemotherapeutic agent Doxorubicin (DOX) is known to cause chemotherapy-induced cognitive impairment (CICI). Maraviroc, a potent C-C chemokine receptor 5 (CCR5) antagonist, shows neuroprotective properties, while its role in CICI remains unclear. This study determined the therapeutic potential of maraviroc on CICI. Adult C57BL/6J mice with implanted breast cancer cells received four weekly intraperitoneal injections of saline (Control group), 5 mg/kg DOX (DOX group), 10 mg/kg maraviroc (MVC group), or 5 mg/kg DOX with 10 mg/kg maraviroc (DOX + MVC group). The Morris Water Maze (MWM) was used for neurobehavioural test. Western blot analysis and immunofluorescence were used to evaluate the expressions of inflammatory markers, apoptosis-related proteins, and synaptic-related proteins. The volume and weight of tumor were also evaluated after treatments. DOX treatment significantly increased chemokines (CCL3, CCL4) and inflammatory cytokines (IL-1ß, TNF-α) in tumor-bearing mice hippocampus. While maraviroc administration reduced hippocampal proinflammatory factors compared to the DOX group. Furthermore, it also lowered apoptosis markers, restored synaptic proteins levels, and inhibited the NF-κB/NLRP3 pathway. Accordingly, maraviroc treatment significantly improved DOX-induced neurobehavioural impairments as evidenced by an increased number of platform crossings and percentage of target quadrant time in the MWM test. Additionally, when combined with DOX, maraviroc had additional inhibitory effects on tumor growth. These findings suggest that maraviroc can mitigate DOX-induced CICI by suppressing elevated proinflammatory chemokines and cytokines through the NF-κB/NLRP3 pathway, potentially offering an anti-tumor benefit. This research presents a promising therapeutic approach for DOX-induced CICI, enhancing the safety and efficacy of cancer treatments.

Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer.

Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

Contrasting effects of music therapy and aromatherapy on perioperative anxiety: A systematic review and meta-analysis.

INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them. METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737). RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; P =.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; P =.02), while those at 4 hours after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; P <.001). CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicates that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.

Dexmedetomidine promotes colorectal cancer progression via Piwil2 signaling.

PURPOSE: α2-adrenoceptor agonist dexmedetomidine (DEX) has been reported to promote tumorigenesis. Stem-cell protein Piwil2 is associated with cancer progression. Whether Piwil2 plays a role in tumor-promoting effects of DEX is unknown. METHODS: We examined the expression of Piwil2 in human colorectal cancer (CRC) cell lines with/without DEX treatment. We also studied the roles of Piwil2 in proliferation, invasion, migration, as well as expressions of epithelial-mesenchymal transition (EMT)-related proteins in DEX-treated in vitro and in vivo CRC models. And the experiments with genetic and pharmacological treatments were conducted to investigate the underlying molecular mechanism. RESULTS: RNA-sequencing (RNA-seq) analysis found Piwil2 is one of most upregulated genes upon DEX treatment in CRC cells. Furthermore, Piwil2 protein levels significantly increased in DEX-treated CRC cancer cells, which promoted proliferation, invasion, and migration in both CRC cell lines and human tumor xenografts model. Mechanistically, DEX increased nuclear factor E2-related factor 2 (Nrf2) expression, which enhanced Piwil2 transcription via binding to its promoter. Furthermore, in vitro experiments with Piwil2 knockdown or Siah2 inhibition indicated that DEX promoted EMT process and tumorigenesis through Siah2/PHD3/HIF1α pathway. The experiments with another α2-adrenoceptor agonist Brimonidine and antagonists yohimbine and atipamezole also suggested the role of Piwil2 signaling in tumor-promoting effects via an α2 adrenoceptor-dependent manner. CONCLUSION: DEX promotes CRC progression may via activating α2 adrenoceptor-dependent Nrf2/Piwil2/Siah2 pathway and thus EMT process. Our work provides a novel insight into the mechanism underlying tumor-promoting effects of α2-adrenoceptor agonists.

Diagnostic Value of Transabdominal Ultrasonography in Gastrointestinal Malignant Tumors.

Objective: To explore the application value of transabdominal ultrasonography in the diagnosis of gastrointestinal malignant tumors. Methods: This study retrospectively analyzed the transabdominal ultrasound imaging data of 284 patients with gastrointestinal tumors admitted to our hospital from April 2019 to March 2022 and assessed the accuracy of transabdominal ultrasound in diagnosing different types of gastrointestinal tumor diseases. The diagnostic accuracy of transabdominal ultrasonography for TNM staging of gastrointestinal malignancies was calculated. Results: The sensitivity and specificity of transabdominal ultrasonography in the diagnosis of gastric cancer were (82.40% and 83.72%, respectively), colon cancer (77.78% and 88.35%, respectively), gastric stromal tumor (95.45% and 93.65%, respectively), gastric lymphoma (72.22% and 94.66%, respectively), colorectal lymphoma (80.00% and 95.42%, respectively), gastric mucosal hypertrophy (85.71% and 96.69%, respectively), and pyloric hypertrophy (92.59% and 97.79%, respectively). Among the 284 patients included, 152 patients had malignant tumors, including 34 patients with stage I, 30 patients with stage II, 51 patients with stage III, and 37 patients with stage IV. The accuracy of transabdominal ultrasonography for TNM staging of gastrointestinal malignancies was 85.53% (130/152). Conclusion: Transabdominal ultrasonography shows promise as a diagnostic tool for gastrointestinal malignant tumors; however, it is recommended to be used in conjunction with other detection methods such as fibrous gastrointestinal tract examination to minimize the risk of missed diagnoses and misdiagnoses. The study highlights the potential of transabdominal ultrasonography as a non-invasive and accessible diagnostic method for gastrointestinal malignancies. Further research and advancements in imaging technologies are crucial for enhancing diagnostic capabilities and improving patient outcomes in the future.

Direct and Inverse Spin Splitting Effects in Altermagnetic RuO2.

Recently, the altermagnetic materials with spin splitting effect (SSE), have drawn significant attention due to their potential to the flexible control of the spin polarization by the Néel vector. Here, the direct and inverse altermagnetic SSE (ASSE) in the (101)-oriented RuO2 film with the tilted Néel vector are reported. First, the spin torque along the x-, y-, and z-axis is detected from the spin torque-induced ferromagnetic resonance (ST-FMR), and the z-spin torque emerges when the electric current is along the [010] direction, showing the anisotropic spin splitting of RuO2. Further, the current-induced modulation of damping is used to quantify the damping-like torque efficiency (ξDL) in RuO2/Py, and an anisotropic ξDL is obtained and maximized for the current along the [010] direction, which increases with the reduction of the temperature, indicating the present of ASSE. Next, by way of spin pumping measurement, the inverse altermagnetic spin splitting effect (IASSE) is studied, which also shows a crystal direction-dependent anisotropic behavior and temperature-dependent behavior. This work gives a comprehensive study of the direct and inverse ASSE effects in the altermagnetic RuO2, inspiring future altermagnetic materials and devices with flexible control of spin polarization.

Mechanisms of Ferroptosis-Related Genes in Gallbladder Cancer Based on Bioinformatics Analysis.

Gallbladder Cancer (GBC) is a lethal malignancy with limited treatment options and poor prognosis. Recent studies have emphasized the role of ferroptosis, a regulated form of cell death, in various cancers, including GBC. We applied bioinformatics methodologies on four GBC datasets to identify differentially expressed genes (DEGs). An intersection of DEGs from the four datasets with ferroptosis and GBC-associated genes was done to identify key ferroptosis-related genes in GBC. GSVA pathway enrichment analysis and immune cell infiltration assessment were conducted to explore their functional roles and interactions. Seven ferroptosis-related genes, EZH2, MUC1, PVT1, GOT1, CDO1, LIFR, and TFAP2A, were identified to be related to GBC. These genes were associated with vital signaling pathways like the G2/M checkpoint and DNA repair and showed significant correlations with immune cell infiltration in GBC. Receiver Operating Characteristic (ROC) curve analysis revealed their high diagnostic potential, with Area Under the Curve (AUC) values ranging from 0.796 to 0.953. Our findings underscore the pivotal role of ferroptosis in GBC and the potential of ferroptosis-related genes as diagnostic biomarkers. This study lays a foundation for further research into ferroptosis-based therapeutic strategies for GBC.

Inhibitors of Inorganic Polyphosphate and Nucleic Acids Attenuate in vitro Thrombin Generation in Plasma from Trauma Patients.

BACKGROUND: Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8) and universal heparin reversal agent 8 (UHRA-8). METHODS: Plasma thrombin generation (calibrated automated thrombogram, CAT), in 56 trauma patients and 39 controls +/- MPI 8 and UHRA-8 (50 µg/mL), was expressed as lag time (LT, minutes), peak height (PH, nM), and time to peak (ttPeak, minutes), with change in LT (ΔLT) and change in ttPeak (ΔttPeak) quantified. Results expressed in median and quartiles [Q1, Q3], Wilcoxon matched-pairs testing, p < 0.05 significant. RESULTS: Trauma patients had greater baseline PH than controls (182.9 [121.0, 255.2]; 120.5 [62.1, 174.8], p < 0.001). MPI 8 treatment prolonged LT and ttPeak in trauma (7.20 [5.88, 8.75]; 6.46 [5.45, 8.93], p = 0.020; 11.28 [8.96, 13.14]; 11.00 [8.95, 12.94], p = 0.029) and controls (7.67 [6.67, 10.50]; 6.33 [5.33, 8.00], p < 0.001; 13.33 [11.67, 15.33]; 11.67 [10.33, 13.33], p < 0.001). UHRA-8 treatment prolonged LT and ttPeak and decreased PH in trauma (9.09 [7.45, 11.33]; 6.46 [5.45, 8.93]; 14.02 [11.78, 17.08]; 11.00 [8.95, 12.94]; 117.4 [74.5, 178.6]; 182.9 [121.0, 255.2]) and controls (9.83 [8.00, 12.33]; 6.33 [5.33, 8.00]; 16.67 [14.33, 20.00]; 11.67 [10.33, 13.33]; 55.3 [30.2, 95.9]; 120.5 [62.1, 174.8]), all p < 0.001. Inhibitor effects were greater for controls (greater ΔLT and ΔttPeak for both inhibitors, p < 0.001). CONCLUSION: PolyP inhibition attenuates thrombin generation, though to a lesser degree in trauma than in controls, suggesting that polyP contributes to accelerated thrombin generation after trauma.

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.

Effects of different sizes of ambient particulate matter and household fuel use on physical function: National cohort study in China.

BACKGROUND: Impact of outdoor and household air pollution on physical function remains unelucidated. This study examined the influence of various ambient particulate sizes (PM1, PM2.5, and PM10) and household fuel usage on physical function. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011 and 2015 were utilized. The physical functional score was computed by summing scores from four tests: grip strength, gait speed, chair stand test, and balance. Multivariate linear and linear mixed-effects models were used to explore the separate and combined effects of PM1, PM2.5, PM10 and household fuel use on physical function in the cross-sectional and longitudinal analyses, respectively, and to further observe the effects of fuel cleanup on physical function in the context of air pollution exposure. RESULTS: Both cross-sectional and longitudinal analyses revealed negative correlations between PM1 (ß = -0.044; 95% CI: -0.084, -0.004), PM2.5 (ß = -0.024; 95% CI: -0.046, -0.001), PM10 (ß = -0.041; 95% CI: -0.054, -0.029), and physical function, with a more pronounced impact observed for fine particulate matter (PM1). Cleaner fuel use was associated with enhanced physical function compared to solid fuels (ß = 0.143; 95% CI: 0.070, 0.216). The presence of air pollutants and use of solid fuels had a negative impact on physical function, while cleaner fuel usage mitigated the adverse effects of air pollutants, particularly in areas with high exposure. CONCLUSION: This study underscores the singular and combined detrimental effects of air pollutants and solid fuel usage on physical function. Addressing fine particulate matter, specifically PM1, and prioritizing efforts to improve household fuel cleanliness in regions with elevated air pollution levels are crucial for preventing physical disability.

Sex ratio shift after frozen single blastocyst transfer in relation to blastocyst morphology parameters.

The sex ratio shift was observed in peoples who underwent ART treatment. Moreover, there is limited evidence on differences in sex ratio between single frozen-thawed blastocyst morphology, insemination type and transfer days. So further research is needed in this area with regard to factors possibly affecting the sex ratio. Retrospective study based on multicenter including two large assisted reproduction centers in Shanghai and Wuhan in China. A total of 6361 singleton delivery offspring after frozen-thawed blastocyst transfer. Propensity score weighting and logistic regression models were used to estimate the associations between blastocyst morphology grading and child sex ratio. The main outcome measures is singleton sex ratio. In our study, the primary outcome measure was sex ratio which was calculated as the proportion of male newborns among all live births. Higher quality blastocysts resulted in a higher sex ratio than single poor-quality frozen-thawed blastocyst transfer. Among the three blastocyst morphological parameters of trophectoderm (TE), Grade A and B were significantly associated with a higher sex ratio than Grade C. The similar trend was observed in both IVF and ICSI treated subgroups. As compared with expansion (4 + 3), expansion degree 6 achieved a higher sex ratio in overall populations and IVF treated subgroup. Transferring blastocysts of day 6 had the highest sex ratio both in IVF group and ICSI group. A 6.95% higher sex ratio in transferring blastocysts of day 5 in IVF group than those in ICSI group. No significant association between inner cell mass degree and sex ratio was observed. However, as compared with IVF treatment, all morphology parameters achieved the similar or the biased sex ratio favoring female in ICSI treated subgroup. Quality of blastocysts was positively associated with sex ratio. TE score and expansion degree rather than ICM were significantly associated with sex ratio at birth. ICSI treatment promotes the biased sex ratio favoring female.

Self-administered generational surveys combine with genetic analysis to reveal foundations of depression in Japanese adults.

BACKGROUND: Major depressive disorder is a prevalent psychiatric illness characterized by mood disturbances and influenced by various environmental and genetic factors, yet its etiology remains largely unknown. METHODS: We profiled a self-reported depressive population in Japan with a focus on sociodemographic background, lifestyle, comorbidities, and genetic background, using data from two cohorts, a population-based cohort and a three-generation cohort, recruited by the Tohoku Medical Megabank Organization until December 2021. RESULTS: Our findings revealed that depression in the Japanese population is strongly associated with certain sociocultural features prevalent in Japan, such as social isolation, neuroticism, and introversion, as well as with well-known risk factors that include age and gender. Environmental factors related to the Great East Japan Earthquake, considered as cohort characteristics, were also strongly associated with the onset of depression. Moreover, using GWAS analysis of whole-genome sequencing data, we identified novel candidate genetic risk variants located on chromosomes 21 and 22 that are associated with depression in Japanese individuals; further validation of these risk variants is warranted. LIMITATIONS: Our study has limitations, including uncertain clinical relevance resulting from the use of self-reported questionnaires for depression assessment. Additionally, the cohort exhibited a population bias, with greater representation of women than men. CONCLUSIONS: Our results provide holistic insights into depression risk factors in Japanese adults, although their associations with depression are correlations. This supports the idea that targeted interventions and individualized approaches are important for addressing depression in the Japanese population.

1H NMR guided isolation of 3-arylisoquinoline alkaloids from Hypecoum erectum L. and their anti-inflammation activity.

Nine 3-arylisoquinoline alkaloids including five undescribed ones, hypectumines A-E (1-5), were isolated from the whole herb of Hypecoum erectum L. with the guidance of 1H-NMR. Their structures were established by a combination of 1D, 2D NMR, and HRESIMS spectrometry. Among them, hypectumines A and B possessed rare urea moieties while hypectumines C and D were characterized by 3-(methylamino)propanoic acid scaffolds. Biological assay demonstrated that alkaloids hypectumine B and 2,3-dimethoxy-N-formylcorydamine had anti-inflammatory effects by inhibiting NO production on LPS-induced RAW264.7 cells with IC50 values of 24.4 and 44.2 µM, respectively. Furthermore, hypectumine B could reduce the expression of pro-inflammatory cytokines TNF-α and IL-6, suggesting it might be a potential candidate for treating inflammatory disease.