OsLCD3 interacts with OsSAMS1 to regulate grain size via ethylene/polyamine homeostasis control.

A fundamental question in developmental biology is how to regulate grain size to improve crop yields. Despite this, little is still known about the genetics and molecular mechanisms regulating grain size in crops. Here, we provide evidence that a putative protein kinase-like (OsLCD3) interacts with the S-adenosyl-L-methionine synthetase 1 (OsSAMS1) and determines the size and weight of grains. OsLCD3 mutation (lcd3) significantly increased grain size and weight by promoting cell expansion in spikelet hull, whereas its overexpression caused negative effects, suggesting that grain size was negatively regulated by OsLCD3. Importantly, lcd3 and OsSAMS1 overexpression (SAM1OE) led to large and heavy grains, with increased ethylene and decreased polyamines production. Based on genetic analyses, it appears that OsLCD3 and OsSAMS1 control rice grain size in part by ethylene/polyamine homeostasis. The results of this study provide a genetic and molecular understanding of how the OsLCD3-OsSAMS1 regulatory module regulates grain size, suggesting that ethylene/polyamine homeostasis is an appropriate target for improving grain size and weight.

A Machine Learning Model for Identifying Sexual Health Influencers to Promote the Secondary Distribution of HIV Self-Testing Among Gay, Bisexual, and Other Men Who Have Sex With Men in China: Quasi-Experimental Study.

BACKGROUND: Sexual health influencers (SHIs) are individuals actively sharing sexual health information with their peers, and they play an important role in promoting HIV care services, including the secondary distribution of HIV self-testing (SD-HIVST). Previous studies used a 6-item empirical leadership scale to identify SHIs. However, this approach may be biased as it does not consider individuals' social networks. OBJECTIVE: This study used a quasi-experimental study design to evaluate how well a newly developed machine learning (ML) model identifies SHIs in promoting SD-HIVST compared to SHIs identified by a scale whose validity had been tested before. METHODS: We recruited participants from BlueD, the largest social networking app for gay men in China. Based on their responses to the baseline survey, the ML model and scale were used to identify SHIs, respectively. This study consisted of 2 rounds, differing in the upper limit of the number of HIVST kits and peer-referral links that SHIs could order and distribute (first round ≤5 and second round ≤10). Consented SHIs could order multiple HIV self-testing (HIVST) kits and generate personalized peer-referral links through a web-based platform managed by a partnered gay-friendly community-based organization. SHIs were encouraged to share additional kits and peer-referral links with their social contacts (defined as "alters"). SHIs would receive US $3 incentives when their corresponding alters uploaded valid photographic testing results to the same platform. Our primary outcomes included (1) the number of alters who conducted HIVST in each group and (2) the number of newly tested alters who conducted HIVST in each. We used negative binomial regression to examine group differences during the first round (February-June 2021), the second round (June-November 2021), and the combined first and second rounds, respectively. RESULTS: In January 2021, a total of 1828 men who have sex with men (MSM) completed the survey. Overall, 393 SHIs (scale=195 and ML model=198) agreed to participate in SD-HIVST. Among them, 229 SHIs (scale=116 and ML model=113) ordered HIVST on the web. Compared with the scale group, SHIs in the ML model group motivated more alters to conduct HIVST (mean difference [MD] 0.88, 95% CI 0.02-2.22; adjusted incidence risk ratio [aIRR] 1.77, 95% CI 1.07-2.95) when we combined the first and second rounds. Although the mean number of newly tested alters was slightly higher in the ML model group than in the scale group, the group difference was insignificant (MD 0.35, 95% CI -0.17 to -0.99; aIRR 1.49, 95% CI 0.74-3.02). CONCLUSIONS: Among Chinese MSM, SHIs identified by the ML model can motivate more individuals to conduct HIVST than those identified by the scale. Future research can focus on how to adapt the ML model to encourage newly tested individuals to conduct HIVST. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2000039632; https://www.chictr.org.cn/showprojEN.html?proj=63068. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-021-11817-2.

Application of Copper-Sulfur Compound Electrode Materials in Supercapacitors.

Supercapacitors (SCs) are a novel type of energy storage device that exhibit features such as a short charging time, a long service life, excellent temperature characteristics, energy saving, and environmental protection. The capacitance of SCs depends on the electrode materials. Currently, carbon-based materials, transition metal oxides/hydroxides, and conductive polymers are widely used as electrode materials. However, the low specific capacitance of carbon-based materials, high cost of transition metal oxides/hydroxides, and poor cycling performance of conductive polymers as electrodes limit their applications. Copper-sulfur compounds used as electrode materials exhibit excellent electrical conductivity, a wide voltage range, high specific capacitance, diverse structures, and abundant copper reserves, and have been widely studied in catalysis, sensors, supercapacitors, solar cells, and other fields. This review summarizes the application of copper-sulfur compounds in SCs, details the research directions and development strategies of copper-sulfur compounds in SCs, and analyses and summarizes the research hotspots and outlook, so as to provide a reference and guidance for the use of copper-sulfur compounds.

An efficient method for detecting membrane protein oligomerization and complex using 05SAR-PAGE.

Oligomerization is an important feature of proteins, which gives a defined quaternary structure to complete the biological functions. Although frequently observed in membrane proteins, characterizing the oligomerization state remains complicated and time-consuming. In this study, 0.05% (w/v) sarkosyl-polyacrylamide gel electrophoresis (05SAR-PAGE) was used to identify the oligomer states of the membrane proteins CpxA, EnvZ, and Ma-Mscl with high sensitivity. Furthermore, two-dimensional electrophoresis (05SAR/sodium dodecyl sulfate-PAGE) combined with western blotting and liquid chromatography-tandem mass spectrometry was successfully applied to study the complex of CpxA/OmpA in cell lysate. The results indicated that 05SAR-PAGE is an efficient, economical, and practical gel method that can be widely used for the identification of membrane protein oligomerization and the analysis of weak protein interactions.

The long-term outcome of CT-guided radiofrequency ablation of the peripheral branches of the trigeminal nerve in trigeminal neuralgia.

Radiofrequency thermocoagulation (RFTC) of the peripheral branches of the trigeminal nerve has been used for trigeminal neuralgia. However, the long-term outcomes of radiofrequency thermocoagulation have not been established. To evaluate the long-term efficacy of RFTC of peripheral branches in patients with refractory trigeminal neuralgia. A retrospective cohort study was conducted in a comprehensive medical center in China. Patients who underwent radiofrequency thermocoagulation of peripheral branches for refractory trigeminal neuralgia from May 2014 to March 2021 were included for analysis. A total of 84 patients with refractory trigeminal neuralgia underwent 105 procedures. BNI I-II which represents treatment success was achieved in 76/84 (90%) patients and 93/105 (89%) procedures. During follow-up, BNI I and II were maintained in 64/76 (84%), 40/73 (55%), 20/67 (30%), 17/65 (26%), 12/61 (20%), and 8/58 (14%) of patients at 1, 2, 3, 4, 5, and 6 years, after the first procedure, respectively. For all the 105 procedures, BNI I and II were maintained in 68/93 (73%), 41/89(46%), 22/82(27%), 15/79 (19%), 8/74 (11%), and 3/72 (4%) at 1, 2, 3, 4, 5, and 6 years, respectively. There is no significant difference between the first and repeat thermocoagulation in terms of immediate (90% vs. 81%, P=0.140) and long-term efficacies (24 months vs.18 months, P=0.266). Radiofrequency thermocoagulation resulted in better long-term outcomes in patients with typical purely paroxysmal pain (24 months vs. 11 months, P=0.033). Radiofrequency ablation of the peripheral branches of the trigeminal nerve might be a safe and effective method in the treatment of refractory trigeminal neuralgia.

Aberrant accumulation of ceramides in mitochondria triggers cell death by inducing autophagy in Arabidopsis.

Sphingolipids are membrane lipids and play critical roles in signal transduction. Ceramides are central components of sphingolipid metabolism that are involved in cell death. However, the mechanism of ceramides regulating cell death in plants remains unclear. Here, we found that ceramides accumulated in mitochondria of accelerated cell death 5 mutant (acd5), and expression of mitochondrion-localized ceramide kinase (ACD5) suppressed mitochondrial ceramide accumulation and the acd5 cell death phenotype. Using immuno-electron microscopy, we observed hyperaccumulation of ceramides in acer acd5 double mutants, which are characterized by mutations in both ACER (alkaline ceramidase) and ACD5 genes. The results confirmed that plants with specific ceramide accumulation exhibited localization of ceramides to mitochondria, resulting in an increase in mitochondrial reactive oxygen species production. Interestingly, when compared with the wild type, autophagy-deficient mutants showed stronger resistance to ceramide-induced cell death. Lipid profiling analysis demonstrated that plants with ceramide accumulation exhibited a significant increase in phosphatidylethanolamine levels. Furthermore, exogenous ceramide treatment or endogenous ceramide accumulation induces autophagy. When exposed to exogenous ceramides, an increase in the level of the autophagy-specific ubiquitin-like protein, ATG8e, associated with mitochondria, where it directly bound to ceramides. Taken together, we propose that the accumulation of ceramides in mitochondria can induce cell death by regulating autophagy.

Altered NCR3 Splice Variants May Result in Deficient NK Cell Function in Renal Cell Carcinoma Patients.

BACKGROUND/AIM: The natural killer (NK) cell function of patients with malignant tumours may be suppressed by deficiency, and the poor prognosis of renal cell carcinoma (RCC) patients may be due to escape from NK cell cytotoxicity, especially with respect to natural cytotoxicity receptors (NCRs) on the NK cell surface. However, the specific mechanism remains unclear. Therefore, in this study, we sought to explore the role of NCR, especially NCR3 splice variants, in the process of NK cell deficiency in RCC patients. MATERIALS AND METHODS: We used flow cytometry to analyse the phenotype of NK cells from the peripheral blood and kidney tumour tissue of RCC patients. The NKp30-mediated NK cell killing function was measured by antibody-dependent cell-mediated cytotoxicity (ADCC) in NK and RCC cell coincubation. We extracted RNA from the peripheral blood mononuclear cells (PBMCs) of RCC patients and renal carcinoma tissue and carried out real-time quantitative PCR to detect the mRNA levels of NKp30a, NKp30b and NKp30c. mRNA expression levels of cytokines (IL-6, IL-8, IL-10, IL-18 and TGF-ß) based on RNA extracted from renal carcinoma tissue and adjacent normal kidney tissues were also measured by real-time quantitative PCR. RESULTS: Regarding the phenotype of NK cells in RCC patients, the proportion of NK cells in tumour tissue was significantly reduced, with changes in the NK cell proportion being most obvious in NKp30+ NK cells. Furthermore, the results of the ADCC function assay showed limited NKp30+ NK cell-mediated cytotoxicity in RCC patients. Through real-time quantitative PCR, we found lower expression of NKp30a and NKp30b, the immunostimulatory splice variants of NCR3 encoding NKp30, in RCC patients. Moreover, expression of activating cytokines (IL-6 and IL-8) in renal cancer tissue was decreased, though inhibitory cytokine (TGF-ß) expression remained unchanged, which may result in an immunosuppressive cytokine microenvironment. CONCLUSION: Decreased expression of immunostimulatory NCR3 splice variants and the inhibitory cytokine microenvironment in RCC patients may contribute to deficient NK cell cytotoxicity and renal carcinoma cell immune escape from NK cell killing, which may provide a theoretical basis for finding new immunotherapeutic targets for RCC.

Embryological observations on seed abortion in Hibiscus syriacus L. and physiological studies on nutrients, enzyme activity and endogenous hormones.

Under natural conditions, most Hibiscus syriacus L. individuals form very few mature seeds or the mature seeds that do form are of poor quality. As a result, seed yield is poor and seeds have low natural germinability. These phenomena strongly hinder utilization of the excellent germplasm resources of H. syriacus. The study has shown that pollen activity and stigma receptivity were high on the day of anthesis, and the pistils and stamens were fertile. Pollen release and stigma receptivity were synchronous. But in styles following self and cross-pollination, pollen tube abnormalities (distortion and twisting of the pollen tubes) and callose deposition were observed. Cross-pollinated pollen tubes elongated faster and fewer pollen tube abnormalities were observed compared with self-pollinated pollen tubes. And during embryo development, abnormalities during the heart-shaped embryo stage led to embryo abortion. Imbalance in antioxidant enzyme activities and low contents of auxin and cytokinin during early stages of embryo development may affect embryo development. Therefore, a low frequency of outcrossing and mid-development embryo abortion may be important developmental causes of H. syriacus seed abortion. Nutrient deficiencies, imbalance in antioxidant enzyme activities, and a high content of abscisic acid at advanced stages of seed development may be physiological causes of seed abortion.

Inhibition of keloid by 32P isotope radiotherapy through suppressing TGF-ß/Smad signaling pathway.

BACKGROUND: Keloid seriously affects the appearance, and is accompanied by some symptoms including pain, burning, itching. Radioactive nuclides such as 32P have been proved to be effective in inhibiting the formation of keloid, but the mechanism remains unclear. METHODS: The keloid animal model was established through keloid tissues implantation. Hematoxylin-Eosin (HE) and Masson staining were performed to investigate histological changes and collagen deposition. The mRNA and protein expression were assessed using RT-PCR and western blotting, respectively. Cell apoptosis and cycle were evaluated through flow cytometry. RESULTS: Both 32P isotope injection and skin path significantly reduced the size of keloid, and inhibited TGF-ß/Smad signaling pathway. SRI-011381, the agonist of TGF-ß/Smad signaling pathway, markedly reversed the influence of 32P isotope on cell proliferation, cell apoptosis, cell cycle of LNCaP cells and TGF-ß/Smad signaling pathway. CONCLUSIONS: 32P isotope injection and skin path greatly reduced the size of keloid, and the TGF-ß/Smad signaling pathway was remarkably inhibited by 32P isotope treatment. The regulation of dermal fibroblast by 32P isotope was reversed by SRI-011381. 32P isotope might inhibit keloid through suppressing TGF-ß/Smad signaling pathway. Our study provides a novel therapeutic strategy for the treatment of keloid.

Clinical efficacy of iodine-125 (125I) seed implantation in patients with iodine-refractory differentiated thyroid cancer.

Patients with radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) are resistant to radioactive iodine-131(131I) treatment, and the clinical treatment for these patients is complex. The implantation of iodine-125 (125I) seeds in the lesion has been successfully applied to treat malignant tumors, but there are few reports on using 125I particles in the treatment of RAIR-DTC. This retrospective study collected data of 92 patients with RAIR-DTC. Patients treated with sorafenib were included in a control group (50 cases with 72 lesions) and patients treated with 125I implantation were included in an observation group (42 cases with 68 lesions). The results showed that compared with those in the control group, the lesion volume was lower and the VVR was higher in the observation group (P<0.05). The Tg and Tg-Ab levels 6 months after treatment were lower than those before treatment in both groups, and the post-treatment Tg and Tg-Ab levels of the observation group were lower than those of the control group (P<0.05). The efficacy, disease control rate, and objective remission rate were not significantly different between the observation group and the control group (P>0.05). Overall survival of patients in the observation group was longer than that in the control group, χ2 = 4.430, P = 0.035. The incidence of total adverse reactions in the observation group was lower than that in the control group (P<0.05). In conclusion, 125I seed implantation is effective in RAIR-DTC treatment as it can prolong the overall survival of patients while maintaining a safe profile.

Identification of Key Influencers for Secondary Distribution of HIV Self-Testing Kits Among Chinese Men Who Have Sex With Men: Development of an Ensemble Machine Learning Approach.

BACKGROUND: HIV self-testing (HIVST) has been rapidly scaled up and additional strategies further expand testing uptake. Secondary distribution involves people (defined as "indexes") applying for multiple kits and subsequently sharing them with people (defined as "alters") in their social networks. However, identifying key influencers is difficult. OBJECTIVE: This study aimed to develop an innovative ensemble machine learning approach to identify key influencers among Chinese men who have sex with men (MSM) for secondary distribution of HIVST kits. METHODS: We defined three types of key influencers: (1) key distributors who can distribute more kits, (2) key promoters who can contribute to finding first-time testing alters, and (3) key detectors who can help to find positive alters. Four machine learning models (logistic regression, support vector machine, decision tree, and random forest) were trained to identify key influencers. An ensemble learning algorithm was adopted to combine these 4 models. For comparison with our machine learning models, self-evaluated leadership scales were used as the human identification approach. Four metrics for performance evaluation, including accuracy, precision, recall, and F1-score, were used to evaluate the machine learning models and the human identification approach. Simulation experiments were carried out to validate our approach. RESULTS: We included 309 indexes (our sample size) who were eligible and applied for multiple test kits; they distributed these kits to 269 alters. We compared the performance of the machine learning classification and ensemble learning models with that of the human identification approach based on leadership self-evaluated scales in terms of the 2 nearest cutoffs. Our approach outperformed human identification (based on the cutoff of the self-reported scales), exceeding by an average accuracy of 11.0%, could distribute 18.2% (95% CI 9.9%-26.5%) more kits, and find 13.6% (95% CI 1.9%-25.3%) more first-time testing alters and 12.0% (95% CI -14.7% to 38.7%) more positive-testing alters. Our approach could also increase the simulated intervention's efficiency by 17.7% (95% CI -3.5% to 38.8%) compared to that of human identification. CONCLUSIONS: We built machine learning models to identify key influencers among Chinese MSM who were more likely to engage in secondary distribution of HIVST kits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR1900025433; https://www.chictr.org.cn/showproj.html?proj=42001.

Effectiveness of percutaneous balloon compression (PBC) in improving physical function and quality of life in trigeminal neuralgia: a retrospective study.

OBJECTIVE: To evaluate the effectiveness of percutaneous balloon compression (PBC) in treating trigeminal neuralgia (TN) and determine improvements in quality of life (QoL) and daily functional status. METHODS: Data from primary TN (pTN) patients treated with PBC from December 2018 to April 2021 were retrospectively analyzed. Short-Form 36 (SF-36) Health Survey and Functional Independence Measure (FIM) assessments were used to evaluate patients' QoL and physical function every 6 months after surgery, and facial pain was evaluated every 3 to 6 months post-surgery. RESULTS: A total of 80 pTN patients were enrolled for analysis. The Barrow Neurological Institute (BNI) scores of I-II were achieved in 67 (83.8%) patients immediately after the surgery. The estimated rates of BNI I-II pain relief at one, two, and three years were 94.2%, 87.6%, and 83.2%, respectively. All aspects of the SF-36 questionnaire were significantly improved after the PBC, especially in terms of role physical (RP), bodily pain (BP), and social functioning (SF). Patients' functional outcomes measured by FIM at the 6-month follow-up examination were 108.6 ± 9.9, which was significantly improved compared with the pretreatment scores (90.8 ± 12.7). There was no difference between the severity of facial numbness in FIM and any item of the SF-36 except RP (P = 0.004) at 6 months after surgery. There was also no difference in SF-36 and FIM between patients with or without facial hyperalgesia. CONCLUSIONS: PBC can produce long-term and stable pain relief and significantly improve the patient's QoL and physical function. However, further well-designed, high-level, evidence-based studies are needed to precisely assess the efficacy of PBC for pTN patients.

Advances in the research of carbon electrodes for perovskite solar cells.

Perovskite solar cells (PSCs) were first proposed in 2009. They have the advantages of low cost, a simple manufacturing process and excellent photoelectric performance. PSC electrodes are mainly made from precious metals such as gold and silver. Still, the cost of precious metals is high and they react with the other components of the PSCs, resulting in the poor stability of the photovoltaic device. Using carbon as an electrode material can both reduce the cost and significantly improve the stability of the photovoltaic device. However, the poor interface contact between the carbon electrode and perovskite and carbon electrode resistance results in poor photovoltaic device photoelectric performance. Finding a way to successfully utilize carbon as an alternative electrode material is a key step toward moving PSCs from the laboratory to industrialization. This paper reviews the application of carbon black, graphite, graphene, carbon nanotubes (CNTs) and composite carbon electrode in PSCs, focusing on progress in the research of doping, structure, interface modification and the production process.

Predictive value of 18F-FDG PET/CT multi-metabolic parameters and tumor metabolic heterogeneity in the prognosis of gastric cancer.

OBJECTIVE: We aimed to investigate the predictive value of pre-treatment 18F-FDG PET/CT multi-metabolic parameters and tumor metabolic heterogeneity for gastric cancer prognosis. METHODS: Seventy-one patients with gastric cancer were included. All patients underwent 18F-FDG PET/CT whole-body scans prior to treatment and had pathologically confirmed gastric adenocarcinomas. Each metabolic parameter, including SUVmax, SUVmean, MTV, and TLG, was collected from the primary lesions of gastric cancer in all patients, and the slope of the linear regression between the MTV corresponding to different SUVmax thresholds (40% × SUVmax, 80% × SUVmax) of the primary lesions was calculated. The absolute value of the slope was regarded as the metabolic heterogeneity of the primary lesions, expressed as the heterogeneity index HI-1, and the coefficient of variance of the SUVmean of the primary lesions was regarded as HI-2. Patient prognosis was assessed by PFS and OS, and a nomogram of the prognostic prediction model was constructed, after which the clinical utility of the model was assessed using DCA. RESULTS: A total of 71 patients with gastric cancer, including 57 (80.3%) males and 14 (19.7%) females, had a mean age of 61 ± 10 years; disease progression occurred in 27 (38.0%) patients and death occurred in 24 (33.8%) patients. Multivariate Cox regression analysis showed that HI-1 alone was a common independent risk factor for PFS (HR: 1.183; 95% CI: 1.010-1.387, P < 0.05) and OS (HR: 1.214; 95% CI: 1.016-1.450, P < 0.05) in patients with gastric cancer. A nomogram created based on the results of Cox regression analysis increased the net clinical benefit for patients. Considering disease progression as a positive event, patients were divided into low-, intermediate-, and high-risk groups, and Kaplan-Meier survival analysis showed that there were significant differences in PFS among the three groups. When death was considered a positive event and patients were included in the low- and high-risk groups, there were significant differences in OS between the two groups. CONCLUSION: The heterogeneity index HI-1 of primary gastric cancer lesions is an independent risk factor for patient prognosis. A nomogram of prognostic prediction models constructed for each independent factor can increase the net clinical benefit and stratify the risk level of patients, providing a reference for guiding individualized patient treatment.

Factors influencing postoperative anxiety and depression following Iodine-131 treatment in patients with differentiated thyroid cancer: A cross-sectional study.

BACKGROUND: Differentiated thyroid cancer (DTC) often seriously impacts patients' lives. Radionuclide Iodine-131 (131I) is widely used in treating patients with DTC. However, most patients know little about radionuclide therapy, and the treatment needs to be performed in a special isolation ward, which can cause anxiety and depression. AIM: To explore anxiety and depression status and their influencing factors after 131I treatment in patients with DTC. METHODS: A questionnaire survey was conducted among postoperative patients with DTC who received 131I treatment at our hospital from June 2020 to December 2022. General patient data were collected using a self-administered demographic characteristics questionnaire. The self-rating depression scale and self-rating anxiety scale were used to determine whether patients were worried about their symptoms and the degree of anxiety and depression. The patients were cate-gorized into anxiety, non-anxiety, depression, and non-depression groups. Single-variable and multiple-variable analyses were used to determine the risk factors for anxiety and depression in patients with thyroid cancer after surgery. RESULTS: A total of 144 patients were included in this study. The baseline mean score of self-rating anxiety and depression scales were 50.06 ± 16.10 and 50.96 ± 16.55, respectively. Notably, 48.62% (70/144) had anxiety and 47.22% (68/144) of the patients had depression. Sex, age, education level, marital status, household income, underlying diseases, and medication compliance significantly differed among groups (P < 0.05). Furthermore, multivariate logistic regression analysis showed that education level, per capita monthly household income, and medication compliance level affected anxiety (P = 0.015, 0.001, and 0.001 respectively. Patient's sex, marital status, and underlying diseases affected depression (P = 0.007, 0.001, and 0.009, respectively). CONCLUSION: Nursing interventions aiming at reducing the risk of anxiety and depression should target unmarried female patients with low education level, low family income, underlying diseases, and poor adherence to medications.

Uranium uptake is mediated markedly by clathrin-mediated endocytosis and induce dose-dependent toxicity in HK-2 cells.

The objective of this study was to explore the endocytosis mechanisms of uranium uptake in HK-2 cells and its toxic effects. Our results demonstrated that uranium exposure impairs redox homeostasis and increases the permeability of the cell membrane and mitochondrial membrane, which may induce cell apoptosis by cytochrome-c leakage. Alkaline phosphatase activity increased after uranium exposure, which may be involved in the process of intracellular mineralisation of uranium, leading to severe cell necrosis. Furthermore, our findings demonstrated that the clathrin-mediated endocytosis process contributed substantially to uranium uptake in HK-2 cells and the total uranium uptake was highly correlated with cell viability, reaching a high correlation coefficient (r = -0.853) according to Pearson correlation analysis. In conclusion, the uptake of uranium into mammalian cells was mainly facilitated by the clathrin-mediated endocytosis pathway and induced dose-dependent cellular toxicity, including redox homeostasis imbalance, membrane injury, cell apoptosis and necrosis.

The Antiangiogenic Effect and Ocular Pharmacology of Novel Modified Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Oxygen-Induced Retinopathy.

Purpose: To evaluate the hypothesis that 3 novel compounds, OXT-328, Q-922, and CL-717 show efficacy in the treatment of oxygen-induced retinopathy (OIR) and whether or not their route of administration is intravitreal, topical, or systemic. Methods: The OIR mouse model, characterized by an avascular area (AVA) and a neovascular area (NVA) of the retina, was used to study retinopathy of prematurity and other retinal diseases characterized by abnormal vessel growth. We measured the effect of our compounds on both the AVA and NVA in whole mounts of mouse retinal tissue. We also evaluated their ability to prevent new vessel formation in chicken chorioallantoic membranes (CAMs). Finally, we measured the in vitro uptake and biodistribution of topically applied CL-717 in human eye explants. Results: In mice with OIR, compared to controls, a single intravitreal administration of Q-922 or OXT-328 significantly reduced both AVA and NVA. CL-717 administered as eye drops over 5 days also reduced AVA and NVA, whereas OXT-328 eye drops had no effect. Q-922 given intraperitoneal (150 mg/kg/day × 5 days) reduced AVA and NVA. Remarkably, explanted human eyes bathed in CL-717 show rapid uptake and biodistribution in ocular tissues. In the chicken CAM model, all 3 compounds reduced the formation of new blood vessels by about one-third. No side effect in mice was observed, except for mild ocular surface irritation with Q-922. Conclusions: Systemic administration of Q-922 or topical administration of CL-717 holds particular promise for a simplified treatment of proliferative retinopathies without the necessity of intravitreal injections.

Post-hospitalization rehabilitation alleviates long-term immune repertoire alteration in COVID-19 convalescent patients.

The global pandemic of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an once-in-a-lifetime public health crisis. Among hundreds of millions of people who have contracted with or are being infected with COVID-19, the question of whether COVID-19 infection may cause long-term health concern, even being completely recovered from the disease clinically, especially immune system damage, needs to be addressed. Here, we performed seven-chain adaptome immune repertoire analyses on convalescent COVID-19 patients who have been discharged from hospitals for at least 6 months. Surprisingly, we discovered lymphopenia, reduced number of unique CDR3s, and reduced diversity of the TCR/BCR immune repertoire in convalescent COVID-19 patients. In addition, the BCR repertoire appears to be activated, which is consistent with the protective antibody titres, but serological experiments reveal significantly lower IL-4 and IL-7 levels in convalescent patients compared to those in healthy controls. Finally, in comparison with convalescent patients who did not receive post-hospitalization rehabilitation, the convalescent patients who received post-hospitalization rehabilitation had attenuated immune repertoire abnormality, almost back to the level of healthy control, despite no detectable clinic demographic difference. Overall, we report the potential long-term immunological impairment for COVID-19 infection, and correction of this impairment via post-hospitalization rehabilitation may offer a new prospect for COVID-19 recovery strategy.

Machine Learning Based on Computed Tomography Pulmonary Angiography in Evaluating Pulmonary Artery Pressure in Patients with Pulmonary Hypertension.

BACKGROUND: Right heart catheterization is the gold standard for evaluating hemodynamic parameters of pulmonary circulation, especially pulmonary artery pressure (PAP) for diagnosis of pulmonary hypertension (PH). However, the invasive and costly nature of RHC limits its widespread application in daily practice. PURPOSE: To develop a fully automatic framework for PAP assessment via machine learning based on computed tomography pulmonary angiography (CTPA). MATERIALS AND METHODS: A machine learning model was developed to automatically extract morphological features of pulmonary artery and the heart on CTPA cases collected between June 2017 and July 2021 based on a single center experience. Patients with PH received CTPA and RHC examinations within 1 week. The eight substructures of pulmonary artery and heart were automatically segmented through our proposed segmentation framework. Eighty percent of patients were used for the training data set and twenty percent for the independent testing data set. PAP parameters, including mPAP, sPAP, dPAP, and TPR, were defined as ground-truth. A regression model was built to predict PAP parameters and a classification model to separate patients through mPAP and sPAP with cut-off values of 40 mm Hg and 55 mm Hg in PH patients, respectively. The performances of the regression model and the classification model were evaluated by analyzing the intraclass correlation coefficient (ICC) and the area under the receiver operating characteristic curve (AUC). RESULTS: Study participants included 55 patients with PH (men 13; age 47.75 ± 14.87 years). The average dice score for segmentation increased from 87.3% ± 2.9 to 88.2% ± 2.9 through proposed segmentation framework. After features extraction, some of the AI automatic extractions (AAd, RVd, LAd, and RPAd) achieved good consistency with the manual measurements. The differences between them were not statistically significant (t = 1.222, p = 0.227; t = -0.347, p = 0.730; t = 0.484, p = 0.630; t = -0.320, p = 0.750, respectively). The Spearman test was used to find key features which are highly correlated with PAP parameters. Correlations between pulmonary artery pressure and CTPA features show a high correlation between mPAP and LAd, LVd, LAa (r = 0.333, p = 0.012; r = -0.400, p = 0.002; r = -0.208, p = 0.123; r = -0.470, p = 0.000; respectively). The ICC between the output of the regression model and the ground-truth from RHC of mPAP, sPAP, and dPAP were 0.934, 0.903, and 0.981, respectively. The AUC of the receiver operating characteristic curve of the classification model of mPAP and sPAP were 0.911 and 0.833. CONCLUSIONS: The proposed machine learning framework on CTPA enables accurate segmentation of pulmonary artery and heart and automatic assessment of the PAP parameters and has the ability to accurately distinguish different PH patients with mPAP and sPAP. Results of this study may provide additional risk stratification indicators in the future with non-invasive CTPA data.

Decompression versus decompression plus fusion for treating degenerative lumbar spinal stenosis: A systematic review and meta-analysis.

BACKGROUND: Degenerative lumbar spinal stenosis (DLSS) is a complex clinical syndrome that leads to spinal compression. Decompression with fusion has been the most commonly used surgical procedure for treating DLSS symptoms for many years. However, the exact role of fusion and its effectiveness in DLSS therapy has recently been debated. OBJECTIVE: The main purpose of this study was to compare the efficacy and safety of decompression alone and decompression plus fusion in the treatment of DLSS with or without spondylolisthesis. STUDY DESIGN: A systematic review and meta-analysis of the therapeutic effects of decompression for DLSS with or without the combination of fusion. METHODS: A literature search in five relevant databases, including Web of Science, PubMed, Embase, Medline, and Cochrane Library was performed from the inception of the database to March 2022. Only randomized controlled trials (RCTs) assessing the comparison between decompression and decompression plus fusion for DLSS were included. RESULTS: A total of seven studies, 894 patients were analyzed in this meta-analysis. Among these, 443 patients were included in the decompression plus fusion group while 451 patients were included in the decompression alone group. Pooled analysis showed that the combination of decompression with fusion had no superior benefits to decompression alone in terms of Oswestry Disability Index (ODI) score in the first 2 years and long-term follow-up after surgery, also no significant difference in the improvement of back and leg pain was found between two groups. Adding fusion to decompression was associated with a longer operation time, higher complication rate, more blood loss, and extended hospital stay. Furthermore, there was no difference in reoperation rates and patients' satisfaction between the two groups at the last follow-up. CONCLUSION: Decompression plus fusion may not be associated with a better clinical outcome in ODI scores and back or leg pain improvement but with a longer duration of operation time, extended hospital stay, and more blood loss.