High androgen level during controlled ovarian stimulation cycle impairs endometrial receptivity in PCOS patients.

PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.

Structural Comparisons, Fluorescence Properties, and Glass-to-Crystal Transformations of Heat-Cooled and Melt-Quenched Zeolitic Imidazolate Framework Glass.

As a representative of zeolitic imidazolate framework glass, agZIF-62 has been reported to be synthesized using a melt-quenching method in which the ZIF-62 crystal is heated to a temperature above the melting point. Interestingly, we unexpectedly found that agZIF-62 can also be synthesized by simple heating at temperatures lower than the melting point, which may be assisted by the release of encapsulated solvent molecules. The structural differences between melt-quenched agZIF-62 (MQ-agZIF-62) and heat-cooled agZIF-62 (HC-agZIF-62) were investigated. The results indicated that MQ-agZIF-62 is closer to the liquid state, while HC-agZIF-62 is closer to the crystal state. Interestingly, their luminescent emissions exhibit significant differences. Compared with the ZIF-62 crystal, MQ-agZIF-62 showed a blue-shift of 14 nm, whereas HC-agZIF-62 showed a red-shift of 9 nm. The emission intensity of agZIF-62 is also significantly stronger than that of ZIF-62; thus, rapid semiquantitative detection of the content of the MOF glass in glass and crystal mixtures can be achieved. In addition, HC-agZIF-62 and MQ-agZIF-62 can transform into ZIF-62 crystals via a solvent-media mechanism. This study provides new insights into ZIF-62 glass.

Inhibition of RAN attenuates influenza a virus replication and nucleoprotein nuclear export.

Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti-IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participate in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified that bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral target.

Benefits of intensive lipid-lowering therapies in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses have investigated the efficacy of lipid-lowering therapies for atherosclerotic cardiovascular disease; however, few have focused on patients with acute coronary syndrome (ACS). This meta-analysis aimed to compare the benefits of intensive lipid-lowering therapy with those of background statin therapy in patients with ACS. METHODS: Searches were performed on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for articles published until April 13, 2023. Randomized controlled trials that compared intensive lipid-lowering therapies and background statin therapies in patients with prior ACS and recorded the outcome of three-point major cardiovascular events (MACE) were included. The risk ratio (RR) with 95% confidence interval (CI) was used as a measure of primary and secondary outcomes. RESULTS: Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83-0.94; p < 0.001), recurrent ACS (RR, 0.82; 95% CI, 0.71-0.96; p = 0.013), nonfatal myocardial infarction (MI) (RR, 0.87; 95% CI, 0.81-0.93; p < 0.001), stroke (RR, 0.83; 95% CI, 0.73-0.94; p = 0.003), and unstable angina-related hospitalization (RR, 0.57; 95% CI, 0.33-0.99; p = 0.046), but not all-cause mortality (RR, 0.94; 95% CI, 0.82-1.07; p = 0.329), cardiovascular disease-related mortality (RR, 0.96; 95% CI, 0.88-1.06; p = 0.457) or coronary revascularization (RR, 0.89; 95% CI, 0.79-1.00; p = 0.057). CONCLUSIONS: Intensive lipid-lowering therapies may reduce the risk of three-point MACE, recurrent ACS, nonfatal MI, stroke, and hospitalization for unstable angina in patients with ACS undergoing background statin therapy. These results may assist in clinical decision-making for the secondary prevention of cardiovascular events to initiate intensive lipid-lowering therapies immediately after ACS.

Lung adenocarcinoma metastatic to the ovary: a retrospective clinicopathological analysis of 17 cases and literature review.

Lung adenocarcinoma metastatic to the ovary is rarely detected in clinical practice, and only a few cases have been reported. Its clinicopathological features, molecular genetics, and prognosis have not been well characterised. The data of 17 patients diagnosed with this disease between 2013 and 2022 were analysed retrospectively. All patients were non-smokers, with a median age of 46 years (range 30-71 years). Unilateral ovarian involvement was more frequent than bilateral involvement (58.8% vs 41.2%). Lesions presented as solid ovarian or mixed cystic and solid masses, and nearly two-thirds of the tumours (11/17, 64.7%) had a diameter greater than 10 cm. Solid adenocarcinoma was the most common histological subtype (9/17, 52.9%), and three of the cases showed abundant intracellular mucin and signet ring cells. Acinar adenocarcinoma was the second most common type (6/17, 35.3%), usually of moderate to poor differentiation. The remaining two cases were identified as micropapillary adenocarcinoma and mucinous adenocarcinoma. Multinodular growth, necrosis, and lymphovascular invasion were observed in half of the cases, and most of them had a marked stromal response. The most prevalent molecular alteration was ALK-rearranged (8/17, 47.1%), followed by EGFR gene mutations (5/17, 29.4%). A total of 34 cases, comprising 17 from the cohort and 17 from the literature, were included in the survival analysis. Patients with ALK-rearranged genes demonstrated an 80.0% 2-year overall survival rate, whereas those without ALK rearrangement exhibited a lower rate of 33.7%. Although there appears to be a potentially better prognosis for patients with ALK-rearranged genes, further cases and an extended follow-up period are necessary to substantiate this observation.

Engineered probiotic Escherichia coli elicits immediate and long-term protection against influenza A virus in mice.

Influenza virus infection remains a major global health problem and requires a universal vaccine with broad protection against different subtypes as well as a rapid-response vaccine to provide immediate protection in the event of an epidemic outbreak. Here, we show that intranasal administration of probiotic Escherichia coli Nissle 1917 activates innate immunity in the respiratory tract and provides immediate protection against influenza virus infection within 1 day. Based on this vehicle, a recombinant strain is engineered to express and secret five tandem repeats of the extracellular domain of matrix protein 2 from different influenza virus subtypes. Intranasal vaccination with this strain induces durable humoral and mucosal responses in the respiratory tract, and provides broad protection against the lethal challenge of divergent influenza viruses in female BALB/c mice. Our findings highlight a promising delivery platform for developing mucosal vaccines that provide immediate and sustained protection against respiratory pathogens.

Association between frozen embryo transfer and childhood allergy: a retrospective cohort study.

RESEARCH QUESTION: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring? DESIGN: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors. RESULTS: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544). CONCLUSION: This study suggests that children born through FET have increased risk of developing food allergy in early childhood.

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OBJECTIVES: To study chest computed tomography (CT) manifestations in neonates with chronic granulomatous disease (CGD) to provide clues for early diagnosis of this disease. METHODS: A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital. RESULTS: Nine neonates with CGD were included, with eight presenting respiratory symptoms as the initial sign. Chest CT findings included: consolidation in all 9 cases; nodules in all 9 cases, characterized by multiple, variably sized scattered nodules in both lungs; masses in 4 cases; cavities in 3 cases; abscesses in 6 cases; bronchial stenosis in 2 cases; pleural effusion, interstitial changes, and mediastinal lymphadenopathy each in 1 case. CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement; no signs of pulmonary emphysema, lung calcification, halo signs, crescent signs, bronchiectasis, or scar lesions were observed. There was no evidence of rib or vertebral bone destruction. Fungal infections were present in 8 of the 9 cases, including 6 with Aspergillus infections; three of these involved mixed infections with Aspergillus, with masses most commonly associated with mixed Aspergillus infections (3/4). CONCLUSIONS: The primary manifestations of neonatal CGD on chest CT are consolidation, nodules, and/or masses, with Aspergillus as a common pathogen. These features can serve as early diagnostic clues for neonatal CGD.

Emergency rescue of a patient with hemorrhagic shock caused by superior mesenteric artery rupture: A case report.

BACKGROUND: Superior mesenteric artery (SMA) injuries rarely occur during blunt abdominal injuries, with an incidence of < 1%. The clinical manifestations mainly include abdominal hemorrhage and peritoneal irritation, which progress rapidly and are easily misdiagnosed. Quick and accurate diagnosis and timely effective treatment are greatly significant in managing emergent cases. This report describes emergency rescue by a multidisciplinary team of a patient with hemorrhagic shock caused by SMA rupture. CASE SUMMARY: A 55-year-old man with hemorrhagic shock presented with SMA rupture. On admission, he showed extremely unstable vital signs and was unconscious with a laceration on his head, heart rate of 143 beats/min, shallow and fast breathing (frequency > 35 beats/min), and blood pressure as low as 20/10 mmHg (1 mmHg = 0.133 kPa). Computed tomography revealed abdominal and pelvic hematocele effusion, suggesting active bleeding. The patient was suspected of partial rupture of the distal SMA branch. The patient underwent emergency mesenteric artery ligation, scalp suture, and liver laceration closure. In view of conditions with acute onset, rapid progression, and high bleeding volume, key points of nursing were conducted, including activating emergency protocol, opening of the green channel, and arranging relevant examinations with various medical staff for quick diagnosis. The seamless collaboration of the multidisciplinary team helped shorten the preoperative preparation time. Emergency laparotomy exploration and mesenteric artery ligation were performed to mitigate hemorrhagic shock while establishing efficient venous accesses and closely monitoring the patient's condition to ensure hemodynamic stability. Strict measures were taken to avoid intraoperative hypothermia and infection. CONCLUSION: After 3.5 h of emergency rescue and medical care, bleeding was successfully controlled, and the patient's condition was stabilized. Subsequently, the patient was transferred to the intensive care unit for continuous monitoring and treatment. On the sixth day, the patient was weaned off the ventilator, extubated, and relocated to a specialized ward. Through diligent medical intervention and attentive nursing, the patient made a full recovery and was discharged on day 22. The follow-up visit confirmed the patient's successful recovery.

Highly intrinsic carrier mobility in tin diselenide crystal accessed with ultrafast terahertz spectroscopy.

Tin diselenide (SnSe2), a layered transition metal dichalcogenide (TMDC), stands out among other TMDCs for its extraordinary photoactive ability and low thermal conductivity. Consequently, it has stimulated many influential researches on photodetectors, ultrafast pulse shaping, thermoelectric devices, etc. However, the carrier mobility in SnSe2, as determined experimentally, remains limited to tens of cm2V-1s-1. This limitation poses a challenge for achieving high-performance SnSe2-based devices. Theoretical calculations, on the other hand, predict that the carrier mobility in SnSe2 can reach hundreds of cm2V-1s-1, approximately one order of magnitude higher than experimental value. Interestingly, the carrier mobility could be underestimated significantly in long-range transportation measurements due to the presence of defects and boundary scattering effects. To address this discrepancy, we employ optic pump terahertz probe spectroscopy to access the photoinduced dynamical THz photoconductivity of SnSe2. Our findings reveal that the intrinsic carrier mobility in conventional SnSe2 single crystal is remarkably high, reaching 353.2 ± 37.7 cm2V-1s-1, consistent with the theoretical prediction. Additionally, dynamical THz photoconductivity measurements reveal that the SnSe2 crystal containing rich defects efficiently capture photoinduced conduction-band electrons and valence-band holes with time constants of ∼20 and ∼200 ps, respectively. Meanwhile, we observe an impulsively stimulated Raman scattering at 0.60 THz. Our study not only demonstrates ultrafast THz spectroscopy as a reliable method for determining intrinsic carrier mobility and detection of low frequency coherent Raman mode in materials but also provides valuable reference for the future application of high-performance SnSe2-based devices.

Exploring the mediating role of calcium homeostasis in the association between diabetes mellitus, glycemic traits, and vascular and valvular calcifications: a comprehensive Mendelian randomization analysis.

BACKGROUND: The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets. METHODS: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders. RESULTS: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension. CONCLUSION: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.

Inhibiting the CB1 receptor in CIH-induced animal model alleviates colon injury.

Obstructive sleep apnea (OSA) can lead to intestinal injury, endotoxemia, and disturbance of intestinal flora. Additionally, as a crucial component of the endocannabinoid system, some studies have demonstrated that cannabinoid 1 (CB1) receptors are closely linked to the multiple organ dysfunction triggered by OSA. However, the role of the CB1 receptor in alleviating OSA-induced colon injury remains unclear. Here, through the construction of the OSA classic model, we found that the colon tissue of chronic intermittent hypoxia (CIH)-induced mice exhibited an overexpression of the CB1 receptor. The results of hematoxylin-eosin staining and transmission electron microscopy revealed that inhibition of the CB1 receptor could decrease the gap between the mucosa and muscularis mucosae, alleviate mitochondrial swelling, reduce microvilli shedding, and promote the recovery of tight junctions of CIH-induced mice. Furthermore, CB1 receptor inhibition reduced the levels of metabolic endotoxemia and inflammatory responses, exhibiting significant protective effects on the colon injury caused by CIH. At the molecular level, through western blotting and real-time polymerase chain reaction techniques, we found that inhibiting the CB1 receptor can significantly increase the expression of ZO-1 and Occludin proteins, which are closely related to the maintenance of intestinal mucosal barrier function. Through 16S rRNA high-throughput sequencing and short-chain fatty acid (SCFA) determination, we found that inhibition of the CB1 receptor increased the diversity of the microbial flora and controlled the makeup of intestinal flora. Moreover, butyric acid concentration and the amount of SCFA-producing bacteria, such as Ruminococcaceae and Lachnospiraceae, were both markedly elevated by CB1 receptor inhibition. The results of the spearman correlation study indicated that Lachnospiraceae showed a positive association with both ZO-1 and Occludin but was negatively correlated with the colon CB1 receptor, IL-1ß, and TNF-α. According to this study, we found that inhibiting CB1 receptor can improve CIH-induced colon injury by regulating gut microbiota, reducing mucosal damage and promoting tight junction recovery. KEY POINTS: •CIH leads to overexpression of CB1 receptor in colon tissue. •CIH causes intestinal flora disorder, intestinal mucosal damage, and disruption of tight junctions. •Inhibition of CB1 receptor can alleviate the colon injury caused by CIH through regulating the gut microbiota, reducing mucosal injury, and promoting tight junction recovery.

Preoperative transthoracic echocardiography does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients.

PURPOSE: The present study aimed to investigate the influence of preoperative TTE on postoperative short-term mortality, surgery delay, as well as other economic and clinical outcomes in Chinese geriatric hip fracture patients. METHODS: This retrospective, matched-cohort study enrolled geriatric hip fracture patients (≥ 60 years) who underwent surgical interventions at our center between 2015 and 2020. The primary exposure was inpatient preoperative TTE. Demographic and clinical data that were reported as risk factors for postoperative mortality were retrieved from the medical data center as the covariates. The primary clinical outcomes were all-cause mortality at 30 days, 90 days, 180 days, and 1 year. Time from hospital presentation to surgery, length of stay (LOS), inpatient cost, frequency of cardiology consultation and coronary angiography (CAG) were also assessed. The propensity score matching (PSM) was performed in a ratio of 1:1. RESULTS: 447 patients were identified and 216 of them received a preoperative TTE (48.3%). After successfully matching 390 patients (87.2%), patients receiving TTE showed significantly higher 30-day mortality (6.6% vs 2.0%, P = 0.044). But no significant difference was found in 90-day, 180-day, and 365-day mortality as well as the 1-year accumulated survival rate. Receipt of TTE was also associated with significant increases in LOS (13.6 days vs 11.4 days, P = 0.017), waiting time for surgery (5.9 days vs 4.3 days, P < 0.001), and lower proportion of receiving surgery within 48 h (7.2% vs. 26.2%, P < 0.001). According to the multivariable logistic analysis, only ejection fraction (30 days, 90 days), aorta diameter (30 days, 90 days, 180 days, 365 days), left ventricular posterior wall diameter (90 days, 180 days, 365 days), aortic valve velocity (90 days) and mitral valve A-peak (90 days, 180 days) were association with postoperative mortality among the 17 parameters in the TTE reports. Besides, TTE has no influence on the frequency of preoperative cardiology consultation. CONCLUSION: Preoperative TTE does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients. The predictive ability of TTE parameters is limited for postoperative mortality.

Liensinine diperchlorate and artemisitene synergistically attenuate breast cancer progression through suppressing PI3K-AKT signaling and their efficiency in breast cancer patient-derived organoids.

Breast cancer (BC) is the most prevalent cancer among women around the world. Finding new and efficient drugs has become a crucial aspect of BC treatment. Liensinine diperchlorate (LIN) and artemisitene (ATT) are natural compounds with potential anti-cancer activities extracted from lotus (Nelumbo nucifera Gaertn) seeds and Artemisia annua, respectively. However, the synergistic anti-breast cancer effectiveness and mechanism of LIN and ATT remain unknown. This study intended to reveal the biological functions and underlying mechanism of combined LIN and ATT treatment in BC. Herein, we first reported that LIN and ATT synergistically mitigated the proliferation, migration as well as invasion of BC cells. Besides, LIN boosted the stimulatory effect of ATT on reactive oxygen species (ROS)-mediated apoptosis in BC cells. Interestingly, LIN and ATT synergistically attenuated the growth of BC patient-derived organoids. Moreover, LIN augmented the inhibitory efficacy of ATT on BC growth in vivo without obvious side effects. Furthermore, the inactivation of PI3K-AKT pathway and its regulated proteins contributed to the therapeutic role of LIN and ATT treatment in BC. Intriguingly, a prediction model constructed as per RNA sequencing data indicated that the combination of LIN and ATT treatment might ameliorate the prognosis of BC patients. In conclusion, our present investigation demonstrated that LIN and ATT synergistically inhibited BC cell proliferation, migration as well as invasion and enhanced ROS-mediated apoptosis via suppressing the PI3K-AKT signaling, and suggested that combining LIN and ATT treatment might be a promising choice for BC therapy.

Olfactory preference of the litchi fruit borer for oviposition on two litchi varieties.

BACKGROUND: The litchi fruit borer Conopomorpha sinensis Bradley is a major destructive pest of litchi and longan plants in China, India and South East Asia. Given its strong olfactory-based oviposition behaviour, interfering with the chemical communication between this insect pest and its host plant may serve as a potential control strategy. However, the chemical compounds associated with its egg-laying behaviour remain poorly understood. RESULTS: In this study, we investigated the olfactory preference of female C. sinensis for oviposition on intact mature fruits of the Feizixiao (FZX) and Guiwei (GW) varieties. Results showed that female C. sinensis preferred to lay eggs on FZX compared with GW fruits, and this preference was olfactory-induced. In addition, we identified differences in the chemical composition of the volatile blend and proportions between FZX and GW fruits, with terpenes being the main volatile components contributing to this divergence. Compounds that induced electrophysiological activity in female borers were subsequently screened from FZX. d-Limonene exhibited the strongest oviposition attraction among four candidates. Furthermore, this compound served as a volatile olfactory cue for recognition and orientation in female C. sinensis. CONCLUSION: The results of this study provide a deeper understanding of the olfactory preferences of female C. sinensis for oviposition on specific litchi varieties. © 2024 Society of Chemical Industry.

Novel artesunate and isatin hybrid CT3-1 suppresses collagen-induced arthritis through abrogating dendritic cell chemotaxis-induced by CCR5.

BACKGROUND: Chemotaxis and trafficking of dendritic cells (DCs) induced by cytokine receptors are crucial steps in rheumatoid arthritis (RA) pathogenesis. C-C chemokine receptor type 5 (CCR5) plays a key role in DC movement and has been implicated in multitudinous inflammatory and immunology diseases. Thus, targeting CCR5 to suppress DC chemotaxis is considered as a potential strategy for the management of RA. METHODS: Herein, we first synthesized a new hybrid named CT3-1 which based on artesunate and isatin. Besides, we studied the regulating effectiveness of CT3-1 on bone marrow-derived DCs (BMDCs) and on collagen-induced arthritis (CIA) through RNA-seq analysis, cell function experiments in vitro and mice model in vivo. RESULTS: The results shown that CT3-1 mainly reduced CCR5 expression of immature BMDCs and importantly inhibited immature BMDC migration induced by CCR5 in vitro, with no or minor influence on other functions of DCs, such as phagocytosis and maturation. In the mouse model, CT3-1 relieved arthritis severity and inhibited CIA development. Furthermore, CT3-1 intervention decreased the expression of CCR5 in DCs and reduced the proportion of DCs in the peripheral blood of CIA mice. CONCLUSIONS: Our findings suggest that CCR5-induced chemotaxis and trafficking of immature DCs are important in RA. Targeting CCR5 and inhibiting immature DC chemotaxis may provide a novel choice for the treatment of RA and other similar autoimmune diseases. Moreover, we synthesized a new hybrid compound CT3-1 that could inhibit immature DC trafficking and effectively relieve RA by directly reducing the CCR5 expression of immature DCs.

The relative contribution of PM2.5 components to the obstructive ventilatory dysfunction-insights from a large ventilatory function examination of 305,022 workers in southern China.

BACKGROUND: The new round of WHO/ILO Joint Estimates of the Work-related Burden of Disease assessment requires futher research to provide more evidence, especially on the health impact of ambient air pollution around the workplace. However, the evidence linking obstructive ventilatory dysfunction (OVD) to fine particulate matter (PM2.5) and its chemical components in workers is very limited. Evidence is even more scarce on the interactive effects between occupational factors and particle exposures. We aimed to fill these gaps based on a large ventilatory function examination of workers in southern China. METHODS: We conducted a cross-sectional study among 363,788 workers in southern China in 2020. The annual average concentration of PM2.5 and its components were evaluated around the workplace through validated spatiotemporal models. We used mixed-effect models to evaluate the risk of OVD related to PM2.5 and its components. Results were further stratified by basic characteristics and occupational factors. FINDINGS: Among the 305,022 workers, 119,936 were observed with OVD. We found for each interquartile range (IQR) increase in PM2.5 concentration, the risk of OVD increased by 27.8 (95 % confidence interval (CI): 26.5-29.2 %). The estimates were 10.9 % (95 %CI: 9.7-12.1 %), 15.8 % (95 %CI: 14.5-17.2 %), 2.6 % (95 %CI: 1.4-3.8 %), 17.1 % (95 %CI: 15.9-18.4 %), and 11 % (95 %CI: 9.9-12.2 %), respectively, for each IQR increment in sulfate, nitrate, ammonium salt, organic matter and black carbon. We observed greater effect estimates among females, younger workers, workers with a length of service of 24-45 months, and professional skill workers. Furthermore, it is particularly noteworthy that the noise-exposed workers, high-temperature-exposed workers, and less-dust-exposed workers were at a 5.7-68.2 % greater risk than others. INTERPRETATION: PM2.5 and its components were significantly associated with an increased risk of OVD, with stronger links among certain vulnerable subgroups.

Terahertz Biosensor Engineering Based on Quasi-BIC Metasurface with Ultrasensitive Detection.

Terahertz (THz) sensors have attracted great attention in the biological field due to their nondestructive and contact-free biochemical samples. Recently, the concept of a quasi-bound state in the continuum (QBIC) has gained significant attention in designing biosensors with ultrahigh sensitivity. QBIC-based metasurfaces (MSs) achieve excellent performance in various applications, including sensing, optical switching, and laser, providing a reliable platform for biomaterial sensors with terahertz radiation. In this study, a structure-engineered THz MS consisting of a "double C" array has been designed, in which an asymmetry parameter α is introduced into the structure by changing the length of one subunit; the Q-factor of the QBIC device can be optimized by engineering the asymmetry parameter α. Theoretical calculation with coupling equations can well reproduce the THz transmission spectra of the designed THz QBIC MS obtained from the numerical simulation. Experimentally, we adopt an MS with α = 0.44 for testing arginine molecules. The experimental results show that different concentrations of arginine molecules lead to significant transmission changes near QBIC resonant frequencies, and the amplitude change is shown to be 16 times higher than that of the classical dipole resonance. The direct limit of detection for arginine molecules on the QBIC MS reaches 0.36 ng/mL. This work provides a new way to realize rapid, accurate, and nondestructive sensing of trace molecules and has potential application in biomaterial detection.

Sesamolin serves as an MYH14 inhibitor to sensitize endometrial cancer to chemotherapy and endocrine therapy via suppressing MYH9/GSK3ß/ß-catenin signaling.

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecological cancers. Herein, we aimed to define the role of specific myosin family members in EC because this protein family is involved in the progression of various cancers. METHODS: Bioinformatics analyses were performed to reveal EC patients' prognosis-associated genes in patients with EC. Furthermore, colony formation, immunofluorescence, cell counting kit 8, wound healing, and transwell assays as well as coimmunoprecipitation, cycloheximide chase, luciferase reporter, and cellular thermal shift assays were performed to functionally and mechanistically analyze human EC samples, cell lines, and a mouse model, respectively. RESULTS: Machine learning techniques identified MYH14, a member of the myosin family, as the prognosis-associated gene in patients with EC. Furthermore, bioinformatics analyses based on public databases showed that MYH14 was associated with EC chemoresistance. Moreover, immunohistochemistry validated MYH14 upregulation in EC cases compared with that in normal controls and confirmed that MYH14 was an independent and unfavorable prognostic indicator of EC. MYH14 impaired cell sensitivity to carboplatin, paclitaxel, and progesterone, and increased cell proliferation and metastasis in EC. The mechanistic study showed that MYH14 interacted with MYH9 and impaired GSK3ß-mediated ß-catenin ubiquitination and degradation, thus facilitating the Wnt/ß-catenin signaling pathway and epithelial-mesenchymal transition. Sesamolin, a natural compound extracted from Sesamum indicum (L.), directly targeted MYH14 and attenuated EC progression. Additionally, the compound disrupted the interplay between MYH14 and MYH9 and repressed MYH9-regulated Wnt/ß-catenin signaling. The in vivo study further verified sesamolin as a therapeutic drug without side effects. CONCLUSIONS: Herein, we identified that EC prognosis-associated MYH14 was independently responsible for poor overall survival time of patients, and it augmented EC progression by activating Wnt/ß-catenin signaling. Targeting MYH14 by sesamolin, a cytotoxicity-based approach, can be applied synergistically with chemotherapy and endocrine therapy to eventually mitigate EC development. This study emphasizes MYH14 as a potential target and sesamolin as a valuable natural drug for EC therapy.

Charge Transfer in Graphene-MoS2 Vertical Heterostructures Tuned by Stacking Order and Substrate-Introduced Electric Field.

Vertical van der Waals heterostructures composed of graphene (Gr) and transition metal dichalcogenides (TMDs) have created a fascinating platform for exploring optical and electronic properties in the two-dimensional limit. Numerous studies have focused on Gr/TMDs heterostructures to elucidate the underlying mechanisms of charge-energy transfer, quasiparticle formation, and relaxation following optical excitation. Nevertheless, a comprehensive understanding of interfacial charge separation and subsequent dynamics in graphene-based heterostructures remains elusive. Here, we have investigated the carrier dynamics of Gr-MoS2 heterostructures (including Gr/MoS2 and MoS2/Gr stacking sequences) grown on a fused silica substrate under varying photoexcitation energies by comprehensive ultrafast means, including time-resolved terahertz (THz) spectroscopy, THz emission spectroscopy, and transient absorption spectroscopy. Our findings highlight the impact of the substrate electric field on the efficiency of modulating the interfacial charge transfer (CT). Specifically, the optical excitation in Gr/MoS2 generates thermal electron injection from the graphene layer into the MoS2 layer with photon energy well below A-exciton of MoS2, whereas the interfacial CT in the MoS2/Gr is blocked by the electric field of the substrate. In turn, photoexcitation of the A exciton above leads to hole transfer from MoS2 to graphene, which occurs for both Gr-MoS2 heterostructures with opposite stacking orders, resulting in the opposite orientations of the interfacial photocurrent, as directly demonstrated by the out-of-phase THz emission. Moreover, we demonstrate that the recombination time of interfacial exciton is approximately ∼18 ps, whereas the defect-assisted interfacial recombination occurs on a time scale of ∼ns. This study provides valuable insights into the interplay between interfacial CT, substrate effects, and defect engineering in Gr-TMDs heterostructures, thereby facilitating the development of next-generation optoelectronic devices.