Developing a Multifunctional Cathode for Photoassisted Lithium-Sulfur Battery.

Integration of solar cell and secondary battery cannot only promote solar energy application but also improve the electrochemical performance of battery. Lithium-sulfur battery (LSB) is an ideal candidate for photoassisted batteries owing to its high theoretical capacity. Unfortunately, the researches related the combination of solar energy and LSB are relatively lacking. Herein, a freestanding photoelectrode is developed for photoassisted lithium-sulfur battery (PALSB) by constructing a heterogeneous structured Au@N-TiO2 on carbon cloths (Au@N-TiO2/CC), which combines multiple advantages. The Au@N-TiO2/CC photoelectrode can produce the photoelectrons to facilitate sulfur reduction during discharge process, while generating holes to accelerate sulfur evolution during charge process, improving the kinetics of electrochemical reactions. Meanwhile, Au@N-TiO2/CC can work as an electrocatalyst to promote the conversion of intermediate polysulfides during charge/discharge process, mitigating induced side reactions. Benefiting from the synergistic effect of electrocatalysis and photocatalysis, PALSB assembled with an Au@N-TiO2/CC photoelectrode obtains ultrahigh specific capacity, excellent rate performance, and outstanding cycling performance. What is more, the Au@N-TiO2/CC assembled PALSB can be directly charged under light illumination. This work not only expands the application of solar energy but also provides a new insight to develop advanced LSBs.

Visualization of the Charging of Water Droplets Sprayed into Air.

Water droplets are spraying into air using air as a nebulizing gas, and the droplets pass between two parallel metal plates with opposite charges. A high-speed camera records droplet trajectories in the uniform electric field, providing visual evidence for the Lenard effect, that is, smaller droplets are negatively charged whereas larger droplets are positively charged. By analyzing the velocities of the droplets between the metal plates, the charges on the droplets can be estimated. Some key observations include: (1) localized electric fields with intensities on the order of 109 V/m are generated, and charges are expected to jump (micro-lightening) between a positively charged larger droplet and the negatively charged smaller droplet as they separate; (2) the strength of the electric field is sufficiently powerful to ionize gases surrounding the droplets; and (3) observations in an open-air mass spectrometer reveal the presence of ions such as N2+, O2+, NO+, and NO2+. These findings provide new insight into the origins of some atmospheric ions and have implications for understanding ionization processes in the atmosphere and chemical transformations in water droplets, advancing knowledge in the field of aerosol science and water microdroplet chemistry.

Therapeutic effect of nicotinamide mononucleotide on Alzheimer's disease through activating autophagy and anti-oxidative stress.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of ß-amyloid (Aß) plaques and neurofibrillary tangles composed of tau protein in the brain. These neuropathological hallmarks contribute to cognitive impairment by inducing neuronal loss in the cerebral cortex and hippocampus. Unfortunately, current therapeutic approaches only target symptomatic relief and do not impede disease progression. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), has emerged as a promising candidate for the treatment of age-related neurodegenerative disorders. NMN supplementation could restore NAD+ levels, thereby alleviating neuronal damage and slowing the progression of AD and other aging-associated diseases. AD is closely associated with autophagic impairment and oxidative stress. Our in vivo experiments demonstrated that NMN could ameliorate pathological and behavioral impairments in AD mice. Specifically, NMN enhanced autophagy and promoted p-tau clearance. Meanwhile, NMN could activate the Nrf2/Keap1/NQO1 pathway, thereby reducing the oxidative stress. Immunofluorescence results demonstrated that NMN could alleviate neuronal damage in AD mice. Furthermore, in vitro results showed that the p-tau clearance and antioxidant stress effects of NMN were suppressed by autophagy inhibitor, chloroquine (CQ) or bafilomycin A1 (BafA1), in Aß-induced PC12 cells. Lastly, when Nrf2 was knocked down, the antioxidant stress, autophagy enhancement, and p-tau clearance effects of NMN were all inhibited. In conclusion, our research indicates that NMN exerts therapeutic effect against AD by activating autophagy and the Nrf2/Keap1/NQO1 pathway through a mutual regulating mechanism of autophagy and antioxidative stress. These findings highlight the promising potential of NMN for the treatment of AD.

Problem-solving model guided by stimulus-organism-response theory: State of mind and coping styles of depressed mothers after cesarean delivery.

BACKGROUND: The use of a problem-solving model guided by stimulus-organism-response (SOR) theory for women with postpartum depression after cesarean delivery may inform nursing interventions for women with postpartum depression. AIM: To explore the state of mind and coping style of women with depression after cesarean delivery guided by SOR theory. METHODS: Eighty postpartum depressed women with cesarean delivery admitted to the hospital between January 2022 and October 2023 were selected and divided into two groups of 40 cases each, according to the random number table method. In the control group, the observation group adopted the problem-solving nursing model under SOR theory. The two groups were consecutively intervened for 12 weeks, and the state of mind, coping styles, and degree of post-partum depression were analyzed at the end of the intervention. RESULTS: The Edinburgh Postnatal Depression Scale and Hamilton Depression Scale-24-item scores of the observation group were lower than in the control group after care, and the level of improvement in the state of mind was higher than that of the control group (P < 0.05). The level of coping with illness in the observation group after care (26.48 ± 3.35) was higher than that in the control group (21.73 ± 3.20), and the level of avoidance (12.04 ± 2.68) and submission (8.14 ± 1.15) was lower than that in the control group (15.75 ± 2.69 and 9.95 ± 1.20), with significant differences (P < 0.05). CONCLUSION: Adopting the problem-solving nursing model using SOR theory for postpartum depressed mothers after cesarean delivery reduced maternal depression, improved their state of mind, and coping level with illness.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

circUQCRC2 promotes asthma progression in children by activating the VEGFA/NF-κB pathway by targeting miR-381-3p.

This study targeted to explore circUQCRC2's role and mechanism in childhood asthma. A mouse model of ovalbumin-induced asthma was established to evaluate the effects of circUQCRC2 on childhood asthma in terms of oxidative stress, inflammation, and collagen deposition. The effects of circUQCRC2 on platelet-derived growth factor-BB (PDGF-BB)-induced smooth muscle cells (SMCs) were evaluated, the downstream mRNA of miRNA and its associated pathways were predicted and validated, and their effects on asthmatic mice were evaluated. circUQCRC2 levels were upregulated in bronchoalveolar lavage fluid of asthmatic mice and PDGF-BB-treated SMCs. Depleting circUQCRC2 alleviated tissue damage in asthmatic mice, improved inflammatory levels and oxidative stress in asthmatic mice and PDGF-BB-treated SMC, inhibited malignant proliferation and migration of SMCs, and improved airway remodeling. Mechanistically, circUQCRC2 regulated VEGFA expression through miR-381-3p and activated the NF-κB cascade. circUQCRC2 knockdown inactivated the NF-κB cascade by modulating the miR-381-3p/VEGFA axis. Promoting circUQCRC2 stimulates asthma development by activating the miR-381-3p/VEGFA/NF-κB cascade. Therefore, knocking down circUQCRC2 or overexpressing miR-381-3p offers a new approach to treating childhood asthma.

Integrated cell wall and transcriptomic analysis revealed the mechanism underlying zinc-induced alleviation of cadmium toxicity in Cosmos bipinnatus.

Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos.

Boron Neutron Capture Therapy-Derived Extracellular Vesicles via DNA Accumulation Boost Antitumor Dendritic Cell Vaccine Efficacy.

Radiated tumor cell-derived extracellular vesicles (RT-EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT-EVs, thus the low abundance of DNA fragments limits immune responses of RT-EVs. Here, this study found that different radiations affected fates of DNA fragments in RT-EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT-EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high-linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs-educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti-tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long-term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine.

Resilience mechanisms of Trichopria drosophilae (Hymenoptera: Diapriinae) under global extreme cooling: insights into parasitic response and physiological adaptation.

Global climate warming and frequent extreme low-temperature events have made it essential to investigate the impact of low temperatures on parasitic wasps to protect and strengthen farmland biodiversity, which in turn enhances the biological control potential of natural enemies such as parasitic wasps. We systematically examined how low-temperature stress affects the parasitic functional response of Trichopria drosophilae to Drosophila suzukii (Diptera: Drosophilidae) pupae. Our findings indicate that the parasitic behavior of T. drosophilae towards D. suzukii pupae aligns with the Holling II functional response model following exposure to different temperatures. Within the temperature range of 8 °C to -8 °C, lower temperatures correlated decreased instantaneous attack rate of T. drosophilae and an increase in processing time. The search constant Q initially increased and then decreased with declining temperatures. Short-term low-temperature stress negatively impacted the parasitic and searching abilities of T. drosophilae but did not alter its parasitic functional response model. Notably, short-term low-temperature stress had minimal effects on the water content, protein content, and total sugar content of male and female T. drosophilae adults. However, as temperatures decreased, the activities of key enzymes, including GAPDH, SOD, T-AOC, and malondialdehyde (MDA), exhibited an initial increase followed by a decrease. Conversely, the activities of LDH and HOAD decreased, while the activities of CAT and POD increased. Further study on the effect of short-term low temperature on T. drosophilae can provide a research basis for the large-scale production and low-temperature refrigeration technology of T. drosophilae, and provide a scientific basis for its efficient use in the field.

Oxygen Vacancy Enabled Electronic Structure Engineering of Pt-WO3 Nanosheets toward Highly Efficient BTEX Sensing.

A Pt nanoparticle-immobilized WO3 material is a promising candidate for catalytic reactions, and the surface and electronic structure can strongly affect the performance. However, the effect of the intrinsic oxygen vacancy of WO3 on the d-band structure of Pt and the synergistic effect of Pt and the WO3 matrix on reaction performance are still ambiguous, which greatly hinders the design of advanced materials. Herein, Pt-decorated WO3 nanosheets with different electronic metal-support interactions are successfully prepared by finely tuning the oxygen vacancy structure of WO3 nanosheets. Notably, Pt-modified WO3 nanosheets annealed at 400 °C exhibit excellent benzene series (BTEX) sensing performance (S = 377.33, 365.21, 348.45, and 319.23 for 50 ppm ethylbenzene, benzene, toluene, and xylene, respectively, at 140 °C), fast response and recovery dynamics (10/7 s), excellent reliability (σ = 0.14), and sensing stability (φ = 0.08%). Detailed structural characterization and DFT results reveal that interfacial Ptδ+-Ov-W5+ sites are recognized as the active sites, and the oxygen vacancies of the WO3 matrix can significantly affect the d-band structure of Pt nanoparticles. Notably, Pt/WO3-400 with improved surface oxygen mobility and medium electronic metal-support interaction facilitates the activation and desorption of BTEX, which contributes to the highly efficient BTEX sensing performance. Our work provides a new insight for the design of high-performance surface reaction materials for advanced applications.

The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

LncRNAH19 acts as a ceRNA of let-7 g to facilitate endothelial-to-mesenchymal transition in hypoxic pulmonary hypertension via regulating TGF-ß signalling pathway.

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. METHODS: In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. RESULTS: Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFßR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFßR1 induced similar effects to H19 deficiency. CONCLUSIONS: In summary, our findings demonstrate that the H19/let-7 g/TGFßR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.

Turnover intention and its related factors of clinical research coordinator in Hunan, China: a cross-sectional study.

To explore the related factors of turnover intention in clinical research coordinators (CRCs) and assess the mediating effects of professional identity on the association between job burnout and turnover intention. In China, CRC has become increasingly common among clinical trial teams in recent years. However, limited published research focused on the status of turnover intention in CRCs. We invited all the 220 CRCs currently working at Hunan Cancer Hospital located in Changsha city in the central south of China from March to June 2018. Participants were asked to complete structured questionnaires regarding basic demographic information, job burnout, professional identity and turnover intention. A total of 202 participants were included in this study, with a response rate of 91.82%. The main reason for turnover intention among CRCs was human resources, followed by communications, management and material resources (per item score in each dimension: 2.14 vs. 2.43 vs. 2.65 vs. 2.83). All the correlations among job burnout, professional identity and turnover intention were statistically significant, with coefficients ranging from -0.197 to 0.615. Multiple liner regression analysis showed that older age, longer workhours per week, and lower level of professional identity were associated with the prevalence of turnover intention among CRCs. Besides, the association between job burnout and turnover intention was fully mediated by professional identity. This study revealed the status and causes of turnover intention among Chinese CRCs. Effective measures on decreasing working time and improving professional identity should be taken in order to reduce CRCs' turnover intention.

Maternal distress, parenting stress, maladaptive parenting and children's problematic media use in China: evidence from 2022 spring in Shanghai.

The COVID-19 lockdown has forced young children to spend more time on media and significantly impacted their mothers' mental health. This study explored how mothers' individual distress influences children's problematic media use during the Shanghai citywide lockdown caused by COVID-19. Data were collected from 1889 Chinese mothers (Mage = 34.69 years, SD = 3.94 years) with preschoolers aged 3-6 years (Mage = 4.38 years, SD = 1.06 years; 49.0% boys) via an online survey. The statistical analyses relied on SPSS Statistics version 26.0 and macro-program PROCESS 3.3. to investigate the associations and mediation analysis among all the study variables. The results indicated a positive association between maternal distress and children's problematic media use, mediated by parenting stress and maladaptive parenting. Specifically, the serial mediation analysis revealed that high levels of maternal distress exacerbate parenting stress, which in turn leads to maladaptive parenting practices. These maladaptive practices subsequently increase problematic media use in preschool children. The findings highlighted that parents need to enhance their ability to manage risk and promote mental health during periods of significant stress and routine disruption to reduce children's problematic media use.

The functional and structural alterations in brain regions related to the fear network model in panic disorder: A resting-state fMRI and T1-weighted imaging study.

Abnormal functional connectivity (FC) within the fear network model (FNM) has been identified in panic disorder (PD) patients, but the specific local structural and functional properties, as well as effective connectivity (EC), remain poorly understood in PD. The purpose of this study was to investigate the structural and functional patterns of the FNM in PD. Magnetic resonance imaging data were collected from 33 PD patients and 35 healthy controls (HCs). Gray matter volume (GMV), degree centrality (DC), regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) were used to identify the structural and functional characteristics of brain regions within the FNM in PD. Subsequently, FC and EC of abnormal regions, based on local structural and functional features, and their correlation with clinical features were further examined. PD patients exhibited preserved GMV, ReHo, and ALFF in the brain regions of the FNM compared with HCs. However, increased DC in the bilateral amygdala was observed in PD patients. The amygdala and its subnuclei exhibited altered EC with rolandic operculum, insula, medial superior frontal gyrus, supramarginal gyrus, opercular part of inferior frontal gyrus, and superior temporal gyrus. Additionally, Hamilton Anxiety Scale score was positively correlated with EC from left lateral nuclei (dorsal portion) of amygdala to right rolandic operculum and left superior temporal gyrus. Our findings revealed a reorganized functional network in PD involving brain regions regulating exteroceptive-interoceptive signals, mood, and somatic symptoms. These results enhance our understanding of the neurobiological underpinnings of PD, suggesting potential biomarkers for diagnosis and targets for therapeutic intervention.

A Highly Stable, Multifunctional Janus Dressing for Treating Infected Wounds.

The limited and unstable absorption of excess exudate is a major challenge during the healing of infected wounds. In this study, a highly stable, multifunctional Janus dressing with unidirectional exudate transfer capacity is fabricated based on a single poly(lactide caprolactone) (PLCL). The success of this method relies on an acid hydrolysis reaction that transforms PLCL fibers from hydrophobic to hydrophilic in situ. The resulting interfacial affinity between the hydrophilic/phobic PLCL fibers endows the Janus structure with excellent unidirectional liquid transfer and high structural stability against repeated stretching, bending, and twisting. Various other functions, including wound status detection, antibacterial, antioxidant, and anti-inflammatory properties, are also integrated into the dressing by incorporating phenol red and epigallocatechin gallate. An in vivo methicillin-resistant Staphylococcus aureus-infected wound model confirms that the Janus dressing, with the capability to remove exudate from the infected site, not only facilitates epithelialization and collagen deposition, but also ensures low inflammation and high angiogenesis, thus reaching an ideal closure rate up to 98.4% on day 14. The simple structure, multiple functions, and easy fabrication of the dressing may offer a promising strategy for treating chronic wounds, rooted in the challenges of bacterial infection, excessive exudate, and persistent inflammation.

LASSO-derived nomogram for early identification of pediatric monogenic lupus.

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97). CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

Yishen Tongbi decoction attenuates inflammation and bone destruction in rheumatoid arthritis by regulating JAK/STAT3/SOCS3 pathway.

Background: Yishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear. Purpose and study design: The purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS). Results: The findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-ß (TGF-ß). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated. Conclusion: Taken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway.

A novel lncRNA LOC101928222 promotes colorectal cancer angiogenesis by stabilizing HMGCS2 mRNA and increasing cholesterol synthesis.

BACKGROUND: Metastasis is the leading cause of mortality in patients with colorectal cancer (CRC) and angiogenesis is a crucial factor in tumor invasion and metastasis. Long noncoding RNAs (lncRNAs) play regulatory functions in various biological processes in tumor cells, however, the roles of lncRNAs in CRC-associated angiogenesis remain to be elucidated in CRC, as do the underlying mechanisms. METHODS: We used bioinformatics to screen differentially expressed lncRNAs from TCGA database. LOC101928222 expression was assessed by qRT-PCR. The impact of LOC101928222 in CRC tumor development was assessed both in vitro and in vivo. The regulatory mechanisms of LOC101928222 in CRC were investigated by cellular fractionation, RNA-sequencing, mass spectrometric, RNA pull-down, RNA immunoprecipitation, RNA stability, and gene-specific m6A assays. RESULTS: LOC101928222 expression was upregulated in CRC and was correlated with a worse outcome. Moreover, LOC101928222 was shown to promote migration, invasion, and angiogenesis in CRC. Mechanistically, LOC101928222 synergized with IGF2BP1 to stabilize HMGCS2 mRNA through an m6A-dependent pathway, leading to increased cholesterol synthesis and, ultimately, the promotion of CRC development. CONCLUSIONS: In summary, these findings demonstrate a novel, LOC101928222-based mechanism involved in the regulation of cholesterol synthesis and the metastatic potential of CRC. The LOC101928222-HMGCS2-cholesterol synthesis pathway may be an effective target for diagnosing and managing CRC metastasis.

Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.