Deep transcranial magnetic stimulation for treatment-resistant depression: A systematic review and meta-analysis of randomized controlled studies.

The efficacy and safety of deep transcranial magnetic stimulation (dTMS) in treating treatment-resistant depression (TRD) are unknown. Up to June 21, 2023, we conducted a systematic search for RCTs, and then extracted and synthesized data using random effects models. Five RCTs involving 507 patients with TRD (243 in the active dTMS group and 264 in the control group) were included in the present study. The active dTMS group showed significantly higher study-defined response rate (45.3% versus 24.2%, n = 507, risk ratio [RR] = 1.87, 95% confidence interval [CI]: 1.21-2.91, I2 = 53%; P = 0.005) and study-defined remission rate (38.3% versus 14.4%, n = 507, RR = 2.37, 95%CI: 1.30-4.32, I2 = 58%; P = 0.005) and superiority in improving depressive symptoms (n = 507, standardized mean difference = -0.65, 95%CI: -1.11--0.18, I2 = 82%; P = 0.006) than the control group. In terms of cognitive functions, no significant differences were observed between the two groups. The two groups also showed similar rates of other adverse events and all-cause discontinuations (P > 0.05). dTMS is an effective and safe treatment strategy for the management of patients with TRD.

Functional mechanism of baicalein in alleviating severe acute pancreatitis-acute lung injury by blocking the TLR4/MyD88/TRIF signaling pathway.

Severe acute pancreatitis-acute lung injury (SAP-ALI) is a disease with high mortality. This study aims to explore the mechanism of baicalein on SAP-ALI in rats by blocking toll-like receptor-4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-ß (TRIF) signal pathway. The SAP-ALI rat model was established by intraperitoneal injection of 3% pentobarbital sodium (30 mg/kg), with pancreas and intestines turned over, injected with 3.5% sodium taurocholate backward into the bile-pancreatic duct at 0.1 mL/100 g for 12h, and treated with baicalein, lipopolysaccharide (LPS), miR-182 agomir, or miR-182 antagomir. The TLR4/MyD88/TRIF pathway was activated using LPS in SAP-ALI rats after baicalein treatment. Baicalein attenuated inflammatory cell infiltration, alveolar wall edema, decreased W/D ratio and levels of TLR4, MyD88, and TRIF in the lung tissues, reduced levels of inflammatory factors in pancreatic and lung tissues and BALF, diminished ROS, and elevated GSH, SOD and CAT in pancreatic and lung tissues of SAP-ALI rats. Activation of the TLR4/MyD88/TRIF pathway partly abrogated baicalein-mediated improvements in inflammation and oxidative stress in SAP-ALI rats. miR-182 targeted TLR4. miR-182 suppressed inflammation and oxidative stress in SAP-ALI rats by targeting TLR4. Inhibition of miR-182 partly nullified baicalein-mediated attenuation on inflammation and oxidative stress in SAP-ALI rats. In conclusion, baicalein can inhibit the TLR4/MyD88/TRIF pathway and alleviate inflammatory response and oxidative stress in SAP-ALI rats by upregulating miR-182 and suppressing TLR4, thus ameliorating SAP-ALI.

Sustained release gel based on CT image inspection for treatment of diabetes fundus macular lesions.

Currently, slow-release gel therapy is considered to be an effective treatment for fundus macular disease, but the lack of effective evaluation methods limits its clinical application. Therefore, the purpose of this study was to investigate the application and clinical effect of slow-release gel based on CT image examination in the treatment of diabetic fundus macular disease. CT images of fundus macular lesions were collected in a group of diabetic patients. Then the professional image processing software is used to process and analyze the image and extract the key parameters. A slow-release gel was designed and prepared, and applied to the treatment of diabetic fundus macular disease. CT images before and after treatment were compared and analyzed, and the effect of slow-release gel was evaluated. In a certain period of time after treatment, the lesion size and lesion degree of diabetic fundus macular disease were significantly improved by using slow-release gel therapy with CT image examination. No significant adverse reactions or complications were observed during the treatment. This indicates that the slow-release gel based on CT image examination is a safe, effective and feasible treatment method for diabetic fundus macular disease. This method can help improve the vision and quality of life of patients, and provide a new idea and plan for clinical treatment.

Simultaneous Inversion of Particle Size Distribution, Thermal Accommodation Coefficient, and Temperature of In-Flame Soot Aggregates Using Laser-Induced Incandescence.

Measuring the size distribution and temperature of high-temperature dispersed particles, particularly in-flame soot, holds paramount importance across various industries. Laser-induced incandescence (LII) stands out as a potent non-contact diagnostic technology for in-flame soot, although its effectiveness is hindered by uncertainties associated with pre-determined thermal properties. To tackle this challenge, our study proposes a multi-parameter inversion strategy-simultaneous inversion of particle size distribution, thermal accommodation coefficient, and initial temperature of in-flame soot aggregates using time-resolved LII signals. Analyzing the responses of different heat transfer sub-models to temperature rise demonstrates the necessity of incorporating sublimation and thermionic emission for accurately reproducing LII signals of high-temperature dispersed particles. Consequently, we selected a particular LII model for the multi-parameter inversion strategy. Our research reveals that LII-based particle sizing is sensitive to biases in the initial temperature of particles (equivalent to the flame temperature), underscoring the need for the proposed multi-parameter inversion strategy. Numerical results obtained at two typical flame temperatures, 1100 K and 1700 K, illustrate that selecting an appropriate laser fluence enables the simultaneous inversion of particle size distribution, thermal accommodation coefficient, and initial particle temperatures of soot aggregates with high accuracy and confidence using the LII technique.

Maize root exudates promote Bacillus sp. Za detoxification of diphenyl ether herbicides by enhancing colonization and biofilm formation.

Diphenyl ether herbicides are extensively utilized in agricultural systems, but their residues threaten the health of sensitive rotation crops. Functional microbial strains can degrade diphenyl ether herbicides in the rhizosphere of crops, facilitating the restoration of a healthy agricultural environment. However, the interplay between microorganisms and plants in diphenyl ether herbicides degradation remains unclear. Thus, the herbicide-degrading strain Bacillus sp. Za and the sensitive crop, maize, were employed to uncover the interaction mechanism. The degradation of diphenyl ether herbicides by strain Bacillus sp. Za was promoted by root exudates. The strain induced root exudates re-secretion in diphenyl ether herbicide-polluted maize. We further showed that root exudates enhanced the rhizosphere colonization and the biofilm biomass of strain Za, augmenting its capacity to degrade diphenyl ether herbicide. Root exudates regulated gene fliZ, pivotal in biofilm formation. Wild-type strain Za significantly reduced herbicide toxicity to maize compared to the ZaΔfliZ mutant. Moreover, root exudates promoted strain Za growth and chemotaxis, which was related to biofilm formation. This mutualistic relationship between the microorganisms and the plants demonstrates the significance of plant-microbe interactions in shaping diphenyl ether herbicide degradation in rhizosphere soils.

Control of the Hydroquinone/Benzoquinone Redox State in High-Mobility Semiconducting Conjugated Coordination Polymers.

Conjugated coordination polymers (c-CPs) are unique organic-inorganic hybrid semiconductors with intrinsically high electrical conductivity and excellent charge carrier mobility. However, it remains a challenge in tailoring electronic structures, due to the lack of clear guidelines. Here, we develop a strategy wherein controlling the redox state of hydroquinone/benzoquinone (HQ/BQ) ligands allows for the modulation of the electronic structure of c-CPs while maintaining the structural topology. The redox-state control is achieved by reacting the ligand TTHQ (TTHQ=1,2,4,5-tetrathiolhydroquinone) with silver acetate and silver nitrate, yielding Ag4TTHQ and Ag4TTBQ (TTBQ=1,2,4,5-tetrathiolbenzoquinone), respectively. In spite of sharing the same topology consisting of a two-dimensional Ag-S network and HQ/BQ layer, they exhibit different band gaps (1.5 eV for Ag4TTHQ and 0.5 eV for Ag4TTBQ) and conductivities (0.4 S/cm for Ag4TTHQ and 10 S/cm for Ag4TTBQ). DFT calculations reveal that these differences arise from the ligand oxidation state inhibiting energy band formation near the Fermi level in Ag4TTHQ. Consequently, Ag4TTHQ displays a high Seebeck coefficient of 330 µV/K and a power factor of 10 µW/m ⋅ K2, surpassing Ag4TTBQ and the other reported silver-based c-CPs. Furthermore, terahertz spectroscopy demonstrates high charge mobilities exceeding 130 cm2/V ⋅ s in both Ag4TTHQ and Ag4TTBQ.

Enhancing Skin Injury Repair: Combined Application of PF-127 Hydrogel and hADSC-Exos Containing miR-148a-3p.

The use of exosomes to relieve skin injuries has received considerable attention. The PluronicF-127 hydrogel (PF-127 hydrogel) is a novel biomaterial that can be used to carry biomolecules. This study sought to investigate the impact of exosomes originating from human mesenchymal stem cells (MSCs) developed from adipose tissue (hADSC-Exos) combined with a PF-127 hydrogel on tissue repair and explore the underlying mechanism using in vitro and in vivo experiments. miR-148a-3p is the most expressed microRNA (miRNA) in hADSC-Exos. We found that exosomes combined with the PF-127 hydrogel had a better efficacy than exosomes alone; moreover, miR-148a-3p knockdown lowered its efficacy. In vitro, we observed a significant increase in the tumor-like ability of HUVECs after exosome treatment, which was attenuated after miR-148a-3p knockdown. Furthermore, the effects of miR-148a-3p on hADSC-Exos were achieved through the prevention of PTEN and the triggering of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. In conclusion, our results demonstrated that hADSC-Exos can promote angiogenesis and skin wound healing by delivering miR-148a-3p and have a better effect when combined with the PF-127 hydrogel, which may be an alternative strategy to promote wound healing.

Adipose mesenchymal stem cell-derived exosomes promote skin wound healing in diabetic mice by regulating epidermal autophagy.

Background: Adipose mesenchymal stem cell-derived exosomes (ADSC-Exos) have great potential in the field of tissue repair and regenerative medicine, particularly in cases of refractory diabetic wounds. Interestingly, autophagy plays a role in wound healing, and recent research has demonstrated that exosomes are closely associated with intracellular autophagy in biogenesis and molecular signaling mechanisms. Therefore, this study aimed to investigate whether ADSC-Exos promote the repair of diabetic wounds by regulating autophagy to provide a new method and theoretical basis for the treatment of diabetic wounds. Methods: Western blot analysis and autophagy double-labelled adenovirus were used to monitor changes in autophagy flow in human immortalized keratinocyte cell line (HaCaT) cells. ADSC-Exos were generated from ADSC supernatants via ultracentrifugation. The effectiveness of ADSC-Exos on HaCaT cells was assessed using a live-cell imaging system, cell counting kit-8 and cell scratch assays. The cells were treated with the autophagy inhibitor bafilomycin A1 to evaluate the effects of autophagy on cell function. The recovery of diabetic wounds after ADSC-Exo treatment was determined by calculating the healing rates and performing histological analysis. High-throughput transcriptome sequencing was used to analyze changes in mRNA expression after the treatment of HaCaT cells with ADSC-Exos. Results: ADSC-Exos activated autophagy in HaCaT cells, which was inhibited by high glucose levels, and potentiated their cellular functions. Moreover, ADSC-Exos in combination with the autophagy inhibitor bafilomycin A1 showed that autophagy defects further impaired the biological function of epidermal cells under high-glucose conditions and partially weakened the healing effect of ADSC-Exos. Using a diabetes wound model, we found that ADSC-Exos promoted skin wound healing in diabetic mice, as evidenced by increased epidermal autophagy and rapid re-epithelialization. Finally, sequencing results showed that increased expression of autophagy-related genes nicotinamide phosphoribosyltransferase (NAMPT), CD46, vesicle-associated membrane protein 7 (VAMP7), VAMP3 and eukaryotic translation initiation factor 2 subunit alpha (EIF2S1) may contribute to the underlying mechanism of ADSC-Exo action. Conclusions: This study elucidated the molecular mechanism through which ADCS-Exos regulate autophagy in skin epithelial cells, thereby providing a new theoretical basis for the treatment and repair of skin epithelial damage by ADSC-Exos.

Screening of sustainable supply chain performance evaluation indicators based on the ill-conditioned index cycle method.

The establishment of an evaluation indicator system that can accurately assess the sustainability of a supply chain while further enhancing its performance is vital and relevant. Based on the connotation of sustainable supply chains and triple bottom line theory, indicators are initially proposed from economic, environmental, and social dimensions. To increase the explanatory power of the indicator system and decrease information redundancy, the coefficient of variation is applied to identify the indicators with weak interpretation intensity, the ill-conditioned index cycle method is utilized to filter out indicators with redundant information, and data on 100 Chinese listed companies from 2019 to 2021 are used as samples. A performance evaluation indicator system of sustainable supply chains with 16 indicators is ultimately established. The information interpretation strength index and cumulative information contribution rate verify the rationality of the final indicator system. The outcome demonstrates that this screening method can strengthen the representativeness of the indicator system and rapidly reduce redundancy, leading to the better discrimination of the evaluation results. The findings of this study provide an indicator system and a methodological reference for both companies and policymakers and can aid in the transformation of supply chains toward sustainability.

Targeting STING elicits GSDMD-dependent pyroptosis and boosts anti-tumor immunity in renal cell carcinoma.

While Stimulator-of-interferon genes (STING) is an innate immune adapter cruicial for sensing cytosolic DNA and modulating immune microenvironment, its tumor-promoting role in tumor survival and immune evasion remains largely unknown. Here we reported that renal cancer cells are exceptionally dependent on STING for survival and evading immunosurveillance via suppressing ER stress-mediated pyroptosis. We found that STING is significantly amplified and upregulated in clear cell renal cell carcinoma (ccRCC), and its elevated expression is associated with worse clinical outcomes. Mechanically, STING depletion in RCC cells specifically triggers activation of the PERK/eIF2α/ATF4/CHOP pathway and activates cleavage of Caspase-8, thereby inducing GSDMD-mediated pyroptosis, which is independent of the innate immune pathway of STING. Moreover, animal study revealed that STING depletion promoted infiltration of CD4+ and CD8+ T cells, consequently boosting robust antitumor immunity via pyroptosis-induced inflammation. From the perspective of targeted therapy, we found that Compound SP23, a PROTAC STING degrader, demonstrated comparable efficacy to STING depletion both in vitro and in vivo for treatment of ccRCC. These findings collectively unveiled an unforeseen function of STING in regulating GSDMD-dependent pyroptosis, thus regulating immune response in RCC. Consequently, pharmacological degradation of STING by SP23 may become an attractive strategy for treatment of advanced RCC.

Highly Accurate Determination of the Total Amount of Pb2+ and Pb(OH)+ in a Natural Water Environment Revealed by Dynamic Simulation and DFT Calculation: Benefit from the Electron Inverse Effect of Pt Nanoclusters over Defective g-C3N4.

Although utilizing nanomaterial-modified electrodes for lead ion detection has achieved great success, most of them are carried out under acidic conditions and ignore the variation of Pb(II) speciation at different pH conditions, leading to the potential inaccuracy of Pb(II) detection in a neutral natural water environment. Thus, designing a novel catalyst with high accuracy for the detection of various forms of the total amount of Pb(II) (Pb2+ and Pb(OH)+) in neutral waters is significant. Herein, Pt nanoclusters (Pt NCs) were elaborately constructed and stabilized on the Co single-atom-doped g-C3N4 with abundant N vacancies (Pt NCs/VN-C3N4), which achieved the ultrasensitive detection (102.16 µM µA-1) of Pb(II) in neutral conditions. The dynamic simulation and theoretical calculations reveal that the parallel deposition of Pb2+ and Pb(OH)+ occurs on the electrode surface modified by Pt NCs/VN-C3N4, and the current peaks of Pb(II) are cocontributed by Pb2+ and Pb(OH)+ species. An "electron inverse" phenomenon in Pt NCs/VN-C3N4 from the VN-C3N4 substrate to Pt NCs endows Pt NCs in an electron-rich state, serving as active centers to promote rapid and efficient reduction for both Pb2+ and Pb(OH)+, facilitating the accurate detection of the total amount of Pb(II) in all forms in the actual water environment.

Acellular dermal matrix-assisted tissue expansion for giant congenital melanocytic nevi of the extremities and trunk in pediatric patients.

BACKGROUND: Tissue expansion for treating giant congenital melanocytic nevi (GCMN) is a commonly employed surgical method. However, the procedure's efficacy is often hindered by anatomical and histological characteristics as well as blood supply, particularly in the extremities and trunk. Enhancing expansion efficiency while reducing complications is thus a topic to be investigated, especially for pediatric patients undergoing rapid physical and psychological development with higher risks of non-compliance to medical instructions. OBJECT: To explore the effectiveness of expansion in extremities and trunk by immobilizing the acellular dermal matrix (ADM) in the gravitational force zone of inflating expanders. METHODS: All patients involved in this research underwent ADM-assisted tissue expansion in either the extremities or trunk. ADM was fully flattened, securely fixed to the lower pole of the expander, and subsequently attached to the inner surface of the expanding flap. RESULTS: From 2021 to 2023, a total of nine pediatric patients with GCMN underwent the ADM-assisted tissue expansion. All patients achieved the desired expanding volume without experiencing petechiae, ecchymosis, or skin ulceration in the ADM-covered area. The process was well tolerated by all patients, with no reports of itching, pain, allergic reaction, or fever. During the flap transfer, the ADM was observed to be firmly adhered to the expanding flap with discernible capillary network. CONCLUSION: ADM-assisted tissue expansion demonstrates promise in augmenting expansion efficiency and reducing the time needed for surgical intervention in the extremities and trunk, thereby presenting significant clinical value for pediatric patients afflicted with GCMN.

Volatile communication in plants relies on a KAI2-mediated signaling pathway.

Plants are constantly exposed to volatile organic compounds (VOCs) that are released during plant-plant communication, within-plant self-signaling, and plant-microbe interactions. Therefore, understanding VOC perception and downstream signaling is vital for unraveling the mechanisms behind information exchange in plants, which remain largely unexplored. Using the hormone-like function of volatile terpenoids in reproductive organ development as a system with a visual marker for communication, we demonstrate that a petunia karrikin-insensitive receptor, PhKAI2ia, stereospecifically perceives the (-)-germacrene D signal, triggering a KAI2-mediated signaling cascade and affecting plant fitness. This study uncovers the role(s) of the intermediate clade of KAI2 receptors, illuminates the involvement of a KAI2ia-dependent signaling pathway in volatile communication, and provides new insights into plant olfaction and the long-standing question about the nature of potential endogenous KAI2 ligand(s).

An ARF gene mutation creates flint kernel architecture in dent maize.

Dent and flint kernel architectures are important characteristics that affect the physical properties of maize kernels and their grain end uses. The genes controlling these traits are unknown, so it is difficult to combine the advantageous kernel traits of both. We found mutation of ARFTF17 in a dent genetic background reduces IAA content in the seed pericarp, creating a flint-like kernel phenotype. ARFTF17 is highly expressed in the pericarp and encodes a protein that interacts with and inhibits MYB40, a transcription factor with the dual functions of repressing PIN1 expression and transactivating genes for flavonoid biosynthesis. Enhanced flavonoid biosynthesis could reduce the metabolic flux responsible for auxin biosynthesis. The decreased IAA content of the dent pericarp appears to reduce cell division and expansion, creating a shorter, denser kernel. Introgression of the ARFTF17 mutation into dent inbreds and hybrids improved their kernel texture, integrity, and desiccation, without affecting yield.

Muscle strength and non-alcoholic fatty liver disease/metabolic-associated fatty liver disease.

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology, entitled "Association of low muscle strength with metabolic dysfunction-associated fatty liver disease: A nationwide study". We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD), as well as the mechanisms underlying the correlation and related clinical applications. NAFLD, which is now redefined as MAFLD, is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition, which may contribute to decreased muscle strength. Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/ MAFLD, including insulin resistance, inflammation, sedentary behavior, as well as insufficient vitamin D. Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD. However, studies investigating the relationship between muscle strength and MAFLD are limited. Owing to the shortage of specific medications for NAFLD/MAFLD treatment, early detection is essential. Furthermore, the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy, as well as tailored physical activity.

Long-term fasting induced basal thermogenesis flexibility in female Japanese quails.

Male Japanese quails (Coturnix japonica) have been found to exhibit a three-phase metabolic change when subjected to prolonged fasting, during which basal thermogenesis is significantly reduced. A study had shown that there is a significant difference in the body temperature between male and female Japanese quails. However, whether female Japanese quails also show the same characteristic three-phase metabolic change during prolonged fasting and the underlying thermogenesis mechanisms associated with such changes are still unclear. In this study, female Japanese quails were subjected to prolonged starvation, and the body mass, basal metabolic rate (BMR), body temperature, mass of tissues and organs, body fat content, the state-4 respiration (S4R) and cytochrome c oxidase (CCO) activity in the muscle and liver of these birds were measured to determine the status of metabolic changes triggered by the starvation. In addition, the levels of glucose, triglyceride (TG) and uric acid, and thyroid hormones (T3 and T4) in the serum and the mRNA levels of myostatin (MSTN) and avian uncoupling protein (av-UCP) in the muscle were also measured. The results revealed the existence of a three-phase stage similar to that found in male Japanese quails undergoing prolonged starvation. Fasting resulted in significantly lower body mass, BMR, body temperature, tissues masses and most organs masses, as well as S4R and CCO activity in the muscle and liver. The mRNA level of av-UCP decreased during fasting, while that of MSTN increased but only during Phase I and II and decreased significantly during Phase III. Fasting also significantly lowered the T3 level and the ratio of T3/T4 in the serum. These results indicated that female Japanese quails showed an adaptive response in basal thermogenesis at multiple hierarchical levels, from organismal to biochemical, enzyme and cellular level, gene and endocrine levels and this integrated adjustment could be a part of the adaptation used by female quails to survive long-term fasting.

Jiawei Yanghe Decoction attenuate allergic airway inflammation by suppressing group 2 innate lymphoid cells responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Yanghe Decoction (JWYHD) is modified Yanghe Decoction (YHD). YHD historically utilized as a potent medicinal solution for addressing chronic inflammatory conditions, holds promising therapeutic potential in the treatment of asthma. However, the mechanisms underlying JWYHD's effects on allergic asthma remain unclear. AIM OF THE STUDY: To investigate the therapeutic effect as well as the underlying mechanisms of JWYHD on asthmatic mice. MATERIALS AND METHODS: The ovalbumin (OVA)-induced mouse model was utilized, followed by the administration of JWYHD to allergic asthmatic mice. Subsequently, inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung tissues were conducted. The levels of various cytokines including interleukin (IL)-4, IL-5, IL-13, IL-33, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in BALF, as well as the total immunoglobulin E (IgE) content in serum, were assessed. Lung function and tissue pathology examinations were performed to assess the protective impacts of JWYHD. The chemical components of JWYHD and its lung prototype compounds (referred to the chemical components present in JWYHD that were observed in the lung) were explored by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). RNA-seq analysis revealed the regulation mechanisms of JWYHD treating asthma. Furthermore, the effect of JWYHD on type 2 innate lymphoid cells (ILC2s) in asthmatic mice was detected by flow cytometry and Smart-RNA-seq analysis. Then molecular docking analysis was used to show the interaction between identified compounds and key targets. RESULTS: JWYHD significantly attenuated the airway inflammation of asthmatic mice, reduced the levels of inflammatory cells in BALF, as well the levels of the cytokines IL-4, IL-5, IL-13, IL-33, and TNF-α in BALF and IgE in serum. Airway hyperresponsiveness (AHR) and lung inflammation infiltration were also alleviated by JWYHD. Moreover, RNA-seq analysis revealed that JWYHD attenuated airway inflammation in asthmatic mice via regulating immunity. Flow cytometry confirmed that JWYHD could inhibit ILC2 responses. ILC2 Smart-RNA-seq analysis showed that JWYHD impaired the inflammation reaction-related signaling pathways in ILC2s, and neuropilin-1 (Nrp1), endothelial transcription factor 3 (GATA3) and interleukin 1 receptor like protein 1 (ST2) might be the key targets. The molecular docking analysis investigating the connection between the primary targets and JWYHD's prototype compounds in the lung demonstrated that liquiritin apioside, icariin, glycyrrhizic acid, and uralsaponin B, identified through UPLC-Q-TOF/MS, exhibited significant affinity in binding to the mentioned key targets. CONCLUSION: Our results suggested that the mechanism of JWYHD in treating asthma might be related to limiting ILC2 responses. Our findings provided some pharmacological evidence for the clinical application of JWYHD in the treatment of asthma.

Upregulation of serine metabolism enzyme PSAT1 predicts poor prognosis and promotes proliferation, metastasis and drug resistance of clear cell renal cell carcinoma.

Serine metabolic reprogramming is known to be associated with oncogenesis and tumor development. The key metabolic enzyme PSAT1 has been identified as a potential prognostic marker for various cancers, but its role in ccRCC remains unkown. In this study, we investigated expression of PSAT1 in ccRCC using the TCGA database and clinical specimens. Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT1 increased the susceptibility of sunitinib-resistant cells. Inhibition of PSAT1 increased the sensitivity of drug-resistant tumors to sunitinib in vivo. Collectively, our investigation identifies PSAT1 as an independent prognostic biomarker for advanced ccRCC patients and as a prospective therapeutic target.

Overexpression of MiSPL3a and MiSPL3b confers early flowering and stress tolerance in Arabidopsis thaliana.

SQUAMOSA promoter-binding protein-like (SPL) family genes play an important role in regulating plant flowering and resistance to stress. However, understanding the function of the SPL family in mango is still limited. In a previous study, two MiSPL3 genes, MiSPL3a and MiSPL3b (MiSPL3a/b), were identified in 'SiJiMi' mango and exhibited the highest expression in flowers at the initial flowering stage [24]. Therefore, in this study, we further investigated the expression pattern and gene function of MiSPL3a/b. The results showed that the expression of MiSPL3a was greatest at the end of floral bud differentiation, and MiSPL3b was expressed mainly during the flowering induction and vegetative growth stages. Subcellular localization showed that MiSPL3a/b localized to the nucleus. In addition, ectopic expression of MiSPL3a/b promoted earlier flowering in Arabidopsis thaliana by 3 d-6 d than in wild-type (WT) plants, which increased the expression of SUPPRESSOR OF CONSTANS1 (AtSOC1), FRUITFULL (AtFUL), and APETALA1 (AtAP1). MiSPL3a/b transgenic lines exhibited increased tolerance to drought, GA3, and abscisic acid (ABA) treatments but were sensitive to Pro-Ca treatment. Furthermore, protein interaction analysis revealed that MiSPL3a/b could interact with several stress-related proteins, flowering-related proteins, and the bridge protein 14-3-3. Taken together, MiSPL3a and MiSPL3b acted as positive regulators of flowering time and stress tolerance in transgenic Arabidopsis.

Overexpression of a Ramie (Boehmaeria nivea L. Gaud) Group I WRKY Gene, BnWRKY49, Increases Drought Resistance in Arabidopsis thaliana.

Plants face multiple stresses in their natural habitats. WRKY transcription factors (TFs) play an important regulatory role in plant stress signaling, regulating the expression of multiple stress-related genes to improve plant stress resistance. In this study, we analyzed the expression profiles of 25 BnWRKY genes in three stages of ramie growth (the seedling stage, the rapid-growth stage, and the fiber maturity stage) and response to abiotic stress through qRT-PCR. The results indicated that 25 BnWRKY genes play a role in different growth stages of ramie and were induced by salt and drought stress in the root and leaf. We selected BnWRKY49 as a candidate gene for overexpression in Arabidopsis. BnWRKY49 was localized in the nucleus. Overexpression of BnWRKY49 affected root elongation under drought and salt stress at the Arabidopsis seedling stage and exhibited increased tolerance to drought stress. Further research found that BnWRKY49-overexpressing lines showed decreased stomatal size and increased cuticular wax deposition under drought compared with wild type (WT). Antioxidant enzyme activities of SOD, POD, and CAT were higher in the BnWRKY49-overexpressing lines than the WT. These findings suggested that the BnWRKY49 gene played an important role in drought stress tolerance in Arabidopsis and laid the foundation for further research on the functional analysis of the BnWRKYs in ramie.