Profilin1 Regulates Trophoblast Invasion and Macrophage Differentiation.

Unexplained recurrent spontaneous abortion (URSA) has been associated with the dysfunction of trophoblasts and decidual macrophages. Current evidence suggests that profilin1 (PFN1) plays an important role in many biological processes. However, little is known about whether PFN1 is related to URSA. Herein, the location of PFN1 was detected by immunohistochemistry, and the level of PFN1 was detected by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. The proliferation of trophoblasts was detected by CCK8 and 5-ethynyl-2'-deoxyuridine assays, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays were used to detect apoptosis of trophoblasts. The migration and invasion ability of trophoblasts was assessed by using the wound-healing test and transwell test. Polarization of macrophages was detected in macrophages cultured in trophoblast conditioned medium. PFN1 expression was observed in cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts and was decreased in the villous tissue of patients with URSA. The migration and invasion ability and cell viability of trophoblastic cell lines that underwent PFN1 knockdown significantly decreased, and apoptosis increased. Opposite findings were observed after the overexpression of PFN1 in trophoblastic cells. In addition, PFN1 could regulate trophoblast function through phosphatidylinositol 3-kinase/AKT signal transduction rather than mitogen-activated protein kinase signaling pathways. Finally, knockdown of PFN1 in trophoblasts promoted tumor necrosis factor-α secretion to induce macrophage polarization to M1 phenotype, mediated by the NF-κB signaling pathway. These findings indicate that PFN1 has a broad therapeutic potential for patients with URSA.

Optimization of traction parameters for lumbar scoliosis.

BACKGROUND: Scoliosis is a high incidence disease that endangers the physical and mental health of adolescents. Traction therapy, as a conservative treatment plan, is helpful to improve the recovery speed of patients by studying the influence of different traction factors on the therapeutic effect. METHODS: Based on the thin layer CT data of the lumbar spine of a 16-year-old patient with scoliosis, Mimics21.0 was used to extract the 3D digital model, and Geomagic Wrap2021 was used to perform the smooth surface. After that, SolidWorks was used to manually construct the structures, such as the intervertebral disc, and Ansys17.0 was used to add constraints, ligaments, and other features. Three-factor ANOVA was carried out after an orthogonal experiment that considered traction mode, traction angle, and traction force was finished. RESULTS: ① A three-dimensional biomechanical model of lumbar scoliosis was created. ② The model's correctness was confirmed by comparing it to the corpse and other finite element models, as well as by verifying it under a range of working settings. ③ Traction force (P = 0.000), traction angle (P = 0.000), the interaction between traction force and traction angle (P = 0.000), and the interaction between traction mode and traction angle (P = 0.045) were all significant. ④ The interaction between traction force and traction angle has the most significant effect on Cobb, and traction with a certain angle is better than traditional axial traction. ⑤ Traction mode is not significant, but the interaction between traction mode and traction angle is significant. CONCLUSIONS: A certain angle of traction can aid in improving outcomes and the traction force can be suitably decreased in the clinical formulation of the traction plan. The uniformity of correcting effect is more favorable when higher fixation techniques like positive suspension or traction bed traction are used, as opposed to overhanging traction.

Pterostilbene ameliorates oxidative damage and ferroptosis in human ovarian granulosa cells by regulating the Nrf2/HO-1 pathway.

The survival of ovarian granulosa cells is of great significance to the physiological maintenance of the ovary. Oxidative damage to the ovarian granulosa cells can lead to various diseases related to ovarian dysfunction. Pterostilbene exerts many pharmacological effects, such as anti-inflammatory and cardiovascular protective effects. Moreover, pterostilbene was shown to have antioxidant properties. This study aimed to investigate the effect and underlying mechanism of pterostilbene on oxidative damage in ovarian granulosa cells. Ovarian granulosa cell (OGC) lines COV434 and KGN were exposed to H2O2 to establish an oxidative damage model. After treatment with different concentrations of H2O2 or pterostilbene, the cell viability, mitochondrial membrane potential, oxidative stress, and iron levels were detected, and the expression of ferroptosis-related and Nrf2/HO-1 signaling pathway-related proteins were evaluated. Pterostilbene treatment could effectively improve cell viability, reduce oxidative stress, and inhibit ferroptosis stimulated by H2O2. More importantly, pterostilbene could up-regulate Nrf2 transcription by stimulating histone acetylation, and inhibition of Nrf2 signaling could reverse the therapeutic effect of pterostilbene. In conclusion, this research shows that pterostilbene protects human OGCs from oxidative stress and ferroptosis through the Nrf2/HO-1 pathway.

Identification of 4-hydroxyphenylpyruvate dioxygenase inhibitors by virtual screening, molecular docking, molecular dynamic simulation.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) herbicides control broadleaf and gramineous weeds with better crop safety for corn, sorghum and wheat. Multiple screening models in silico have been established to obtain novel lead compounds as HPPD inhibition herbicides. RESULTS: Topomer comparative molecular field analysis (CoMFA) combined with topomer search technology and Bayesian, genetic approximation functions (GFA) and multiple linear regression (MLR) models generated by calculating different descriptors were constructed for the quinazolindione derivatives of HPPD inhibitors. The coefficient of determination (r2 ) of topomer CoMFA, MLR and GFA were 0.975, 0.970 and 0.968, respectively; all the models established displayed excellent accuracy and high predictive capacity. Five compounds with potential HPPD inhibition were obtained via screening fragment library combined with the validation of the above models and molecular docking studies. After molecular dynamics (MD) validation and absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction, the compound 2-(2-amino-4-(4H-1,2,4-triazol-4-yl) benzoyl)-3-hydroxycyclohex-2-en-1-one not only exhibited stable interactions with the protein but also high solubility and low toxicity, and has potential as a novel HPPD inhibition herbicide. CONCLUSION: In this study, five compounds were obtained through multiple quantitative structure-activity relationship screening. Molecular docking and MD experiments showed that the constructed approach had good screening ability for HPPD inhibitors. This work provided molecular structural information for developing novel, highly efficient and low-toxicity HPPD inhibitors. © 2023 Society of Chemical Industry.

Hypoxia-induced polarization of M2 macrophages and C-C motif chemokine ligand 5 secretion promotes the migration and invasion of trophoblasts†.

In the early stage of pregnancy, hypoxia in the placenta is of great significance to the migration and invasion of trophoblasts. In addition, changes to the polarity and activity of macrophages can affect embryo implantation, trophoblast migration and invasion, and vascular remodeling by affecting cytokine secretion. However, the mechanism of the effects of hypoxic conditions in the placenta on trophoblasts remains unknown. We used gene knockdown on macrophages, and drug treatment on trophoblasts, and cultured them under hypoxic and normoxic conditions. The cells were then subjected to wound-healing assays, Transwell cell invasion experiments, quantitative real-time reverse transcription Polymerase Chain Reaction (PCR), western blotting, and immunofluorescence. The polarization of macrophages in each group, the migration and invasion ability of trophoblasts, and changes to the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were detected. Hypoxic conditions induce M2 polarization of macrophages. The conditioned medium from macrophages under hypoxic conditions increased the migration and invasion of trophoblasts and enhanced the levels of phosphorylated (p)-PI3K and p-AKT in trophoblasts. After C-C motif chemokine ligand 5 knockdown in macrophages, the ability of conditioned medium from macrophages cultured under hypoxic conditions to promote the migration and invasion of trophoblasts was weakened significantly. The use of PI3K/AKT signaling pathway agonists could reverse the attenuation effect caused by C-C motif chemokine ligand 5 knockdown.

Virtual screening based on pharmacophore model for developing novel HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for herbicide design. A multilayered virtual screening workflow was constructed by combining two pharmacophore models based on ligand and crystal complexes, molecular docking, molecular dynamics (MD), and biological activity determination to identify novel small-molecule inhibitors of HPPD. About 110, 000 compounds of Bailingwei and traditional Chinese medicine databases were screened. Of these, 333 were analyzed through docking experiments. Five compounds were selected by analyzing the binding pattern of inhibitors with amino acid residues in the active pocket. All five compounds could produce stable coordination with cobalt ion, and form favorable π-π interactions. MD simulation demonstrated that Phe381 and Phe424 made large contributions to the strength of binding. The enzyme activity experiment verified that compound-139 displayed excellent potency against AtHPPD (IC50 = 0.742 µM), however, compound-5222 had inhibitory effect on human HPPD (IC50 = 6 nM). Compound-139 exhibited herbicidal activity to some extent on different gramineous weeds. This work provided a strong insight into the design and development of novel HPPD inhibitor using in silico techniques.

Diazabicyclo derivatives as safeners protect cotton from injury caused by flumioxazin.

Flumioxazin, a protoporphyrinogen oxidase (PPO; EC 1.3.3.4) inhibitor, has been used in soybean, cotton, grapes, and many other crops to control broad leaf weeds. Unfortunately, it can cause damage to cotton. To ameliorate phytotoxicity of flumioxazin to cotton, this work assessed the protective effects of diazabicyclo derivatives as potential safeners in cotton. A bioactivity assay proved that the phytotoxicity of flumioxazin on cotton was alleviated by some of the compounds. In particular, the activity of glutathione S-transferases (GSTs) was significantly enhanced by Compound 32, which showed good safening activity against flumioxazin injury. The physicochemical properties and absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions proved that the pharmacokinetic properties of Compound 32 are similar to those of the commercial safener BAS 145138. The present work demonstrated that diazabicyclo derivatives are potentially efficacious as herbicide safeners, meriting further investigation.

Computer-Aided and AILDE Approaches to Design Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a pivotal enzyme in tocopherol and plastoquinone synthesis and a potential target for novel herbicides. Thirty-five pyridine derivatives were selected to establish a Topomer comparative molecular field analysis (Topomer CoMFA) model to obtain correlation information between HPPD inhibitory activity and the molecular structure. A credible and predictive Topomer CoMFA model was established by "split in two R-groups" cutting methods and fragment combinations (q2 = 0.703, r2 = 0.957, ONC = 6). The established model was used to screen out more active compounds and was optimized through the auto in silico ligand directing evolution (AILDE) platform to obtain potential HPPD inhibitors. Twenty-two new compounds with theoretically good HPPD inhibition were obtained by combining the high-activity contribution substituents in the existing molecules with the R-group search via Topomer search. Molecular docking results revealed that most of the 22 fresh compounds could form stable π-π interactions. The absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction and drug-like properties made 9 compounds potential HPPD inhibitors. Molecular dynamics simulation indicated that Compounds Y12 and Y14 showed good root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values and stability. According to the AILDE online verification, 5 new compounds with potential HPPD inhibition were discovered as HPPD inhibitor candidates. This study provides beneficial insights for subsequent HPPD inhibitor design.

Profile and outcome of receptor conversion in breast cancer metastases: a nation-wide multicenter epidemiological study.

Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation-wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.0%) patients retesting receptor status for metastasis. Discordance in one or more receptors between the primary and the metastatic biopsy was found in 37.7% of women. Patients who remained hormone receptor (HR) positive in their metastases had similar progression-free survival of first-line and second-line treatment compared to patients with HR conversion (P > .05). In multivariate analysis, patients who showed ER conversion from negative to positive had longer disease-free survival (DFS) than patients who remained negative in their metastases (hazard ratio, 2.05; 95% confidence interval [CI], 1.45-2.90; P < .001). Patients with PR remained positive and had longer DFS than patients with PR conversion from negative to positive (hazard ratio, 0.56; 95% CI, 0.38-0.83; P = .004). Patients with PR conversion have shorter overall survival than patients with PR remained positive or negative (P = .016 and P = .041, respectively). Our findings showed that the receptors' conversions were common in metastatic breast cancer, and the conversion impacted the survival.

B7-H4, a promising target for immunotherapy.

The coinhibitory molecule B7-H4, an important member of the B7 family, is abnormally expressed in tumors, inflammation and autoimmune diseases. B7-H4 negatively regulates T cell immune response and promotes immune escape by inhibiting the proliferation, cytokine secretion, and cell cycle of T cells. Moreover, B7-H4 plays an extremely important role in tumorigenesis and tumor development including cell proliferation, invasion, metastasis, anti-apoptosis, etc. In addition, B7-H4 has the other biological functions, such as protection against type 1 diabetes (T1D) and islet cell transplantation. Therefore, B7-H4 has been identified as a novel marker or a therapeutic target for the treatment of tumors, inflammation, autoimmune diseases, and organ transplantation. Here, we summarized the expression profiles, physiological and pathological functions, and regulatory mechanisms of B7-H4, the signaling pathways involved, as well as B7-H4-based immunotherapy.

Using arterial blood as a substitute for venous blood in routine biochemistry parameter examinations in rabbits.

BACKGROUND: It has been widely accepted that there is a significant difference in peripheral blood oxygen between arteries and veins. Therefore, arterial blood has been collected for blood gas analysis, and venous blood, because it is convenient to collect, has been used for most laboratory examinations. However, venous blood is always difficult to collect in rabbits; in contrast, arterial blood is easier to obtain, and research on whether arterial blood can be used instead of venous blood for routine biochemical parameter examination is rare. Therefore, the present study was designed to explore whether arterial blood can be used as a substitute for venous blood for routine biochemistry parameter examination in rabbits. RESULTS: Three venous blood samples with gross hemolysis were excluded. Venous and arterial blood samples were obtained from forty-two rabbits. Arterial blood samples correlate well with venous blood in alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), total protein (TP), globulin (GLB), serum total cholesterol (TC), serum triglyceride (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), urea (Ur) and creatinine (Cr) levels by Deming regression analysis with slopes ranging from 0.893 to 1.176 and intercepts ranging from - 4.886 to 5.835. Bland-Altman analysis showed that the two sample parameters had 93%-98% of the points within the 95% consistency limits. There were significant differences between venous blood and arterial blood in ALP, TP, TC, TG, HDL, LDL and Cr, while AST, ALT, GGT, GLB and Ur showed no significant differences. CONCLUSIONS: Arterial blood can be a substitute for venous blood in routine biochemistry parameter examinations in rabbits, especially in situations where venous blood is difficult to collect.

Usefulness of the Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Diagnosing Focal Liver Lesions by Inexperienced Radiologists.

OBJECTIVES: To evaluate the usefulness of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) in diagnosing focal liver lesions (FLLs) by inexperienced radiologists. METHODS: Images and clinical data from 258 patients at risk for hepatocellular carcinoma who underwent CEUS were collected retrospectively. Two trained inexperienced radiologists and 2 experienced radiologists reviewed all CEUS clips. Each inexperienced radiologist assigned a CEUS LI-RADS category for each observation and labeled it benign or malignant independently. Each experienced radiologist labeled each lesion malignant or benign independently using a conventional diagnostic method. Interobserver agreement of CEUS LI-RADS was analyzed by the κ test. The overall diagnostic accuracy of the LI-RADS category and conventional diagnosis was described by the sensitivity, specificity, positive predictive value, and negative predictive value. All test results were considered significant at P < .05. RESULTS: A κ value of 0.774 indicated that the CEUS LI-RADS algorithm resulted in substantial consistency between the inexperienced radiologists. For the diagnosis of hepatocellular carcinoma, the sensitivity, specificity, positive predictive value, and negative predictive value were improved significantly in inexperienced radiologists using the CEUS LI-RADS compared to conventional methods. The overall diagnostic accuracy of the experienced radiologists was almost equal to that of CEUS LI-RADS categories assigned by the inexperienced radiologists. CONCLUSIONS: The CEUS LI-RADS algorithm can not only obtain substantial consistency among inexperienced radiologists but also have excellent diagnostic efficacy in the differentiation of benign from malignant FLLs compared to conventional methods. As a comprehensive algorithm, the CEUS LI-RADS can act as a guide for trainees in learning how to diagnose FLLs.

Betel Nut Arecoline Induces Different Phases of Growth Arrest between Normal and Cancerous Prostate Cells through the Reactive Oxygen Species Pathway.

Prostate cancer (PCa) is a reproductive system cancer in elderly men. We investigated the effects of betel nut arecoline on the growth of normal and cancerous prostate cells. Normal RWPE-1 prostate epithelial cells, androgen-independent PC-3 PCa cells, and androgen-dependent LNCaP PCa cells were used. Arecoline inhibited their growth in dose- and time-dependent manners. Arecoline caused RWPE-1 and PC-3 cell cycle arrest in the G2/M phase and LNCaP cell arrest in the G0/G1 phase. In RWPE-1 cells, arecoline increased the expression of cyclin-dependent kinase (CDK)-1, p21, and cyclins B1 and D3, decreased the expression of CDK2, and had no effects on CDK4 and cyclin D1 expression. In PC-3 cells, arecoline decreased CDK1, CDK2, CDK4, p21, p27, and cyclin D1 and D3 protein expression and increased cyclin B1 protein expression. In LNCaP cells, arecoline decreased CDK2, CDK4, and cyclin D1 expression; increased p21, p27, and cyclin D3 expression; had no effects on CDK1 and cyclin B1 expression. The antioxidant N-acetylcysteine blocked the arecoline-induced increase in reactive oxygen species production, decreased cell viability, altered the cell cycle, and changed the cell cycle regulatory protein levels. Thus, arecoline oxidant exerts differential effects on the cell cycle through modulations of regulatory proteins.

Tailoring Biomimetic Phosphorylcholine-Containing Block Copolymers as Membrane-Targeting Cellular Rescue Agents.

Some synthetic polymers can block cell death when applied following an injury that would otherwise kill the cell. This cellular rescue occurs through interactions of the polymers with cell membranes. However, general principles for designing synthetic polymers to ensure strong, but nondisruptive, cell membrane targeting are not fully elucidated. Here, we tailored biomimetic phosphorylcholine-containing block copolymers to interact with cell membranes and determined their efficacy in blocking neuronal death following oxygen-glucose deprivation. By adjusting the hydrophilicity and membrane affinity of poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC)-based triblock copolymers, the surface active regime in which the copolymers function effectively as membrane-targeting cellular rescue agents was determined. We identified nonintrusive interactions between the polymer and the cell membrane that alter the collective dynamics of the membrane by inducing rigidification without disrupting lipid packing or membrane thickness. In general, our results open new avenues for biological applications of polyMPC-based polymers and provide an approach to designing membrane-targeting agents to block cell death after injury.

[Identification of Curcuma herbs using XGBoost algorithm in electronic nose odor fingerprint].

This article aims to identify four commonly applied herbs from Curcuma genus of Zingiberaceae family,namely Curcumae Radix( Yujin),Curcumae Rhizoma( Ezhu),Curcumae Longae Rhizoma( Jianghuang) and Wenyujin Rhizoma Concisum( Pianjianghuang). The odor fingerprints of those four herbal medicines were collected by electronic nose,respectively. Meanwhile,XGBoost algorithm was introduced to data analysis and discriminant model establishment,with four indexes for performance evaluation,including accuracy,precision,recall,and F-measure. The discriminant model was established by XGBoost with positive rate of returning to 166 samples in the training set and 69 samples in the test set were 99. 39% and 95. 65%,respectively. The top four of the contribution to the discriminant model were LY2/g CT,P40/1,LY2/Gh and LY2/LG,the least contributing sensor was T70/2. Compared with support vector machine,random forest and artificial neural network,XGBoost algorithms shows better identification capacity with higher recognition efficiency. The accuracy,precision,recall and F-measure of the XGBoost discriminant model forecast set were 95. 65%,95. 25%,93. 07%,93. 75%,respectively. The superiority of XGBoost in the identification of Curcuma herbs was verified. Obviously,this new method could not only be suitable for digitization and objectification of traditional Chinese medicine( TCM) odor indicators,but also achieve the identification of different TCM based on their odor fingerprint in electronic nose system. The introduction of XGBoost algorithm and more excellent algorithms provide more ideas for the application of electronic nose in data mining for TCM studies.

[A new method on investigate chemical constituents which have anti-thrombin effect by HPLC].

An in vitro anti-thrombin bioassay was developed to investigate the chemical constituents which have anti-thrombin effect from the water soluble components of Salvia miltiorrhiza. Using Chromozym TH as a probe combined with ethyl acetate Semi-micro extraction was applied to measure p-nitroaniline by HPLC. According to the results, the inactivationrate of thrombin by sodium danshensu, salvianolic acid A and salvianolic acid B under a given set of conditions were 3.06%, 77.77% and 2.35%, respectively. In the water-soluble components, salvianolic acid A has a direct inhibition of thrombin, while sodium danshensu and salvianolic acid B have no significant effect on thrombin. The method is sensitive and low consumption. It can eliminate the interference absorbed for the sample itself which can be used for screening single or multiple direct antithrombin active ingredient of herbal extract.

FADD is essential for glucose uptake and survival of thymocytes.

Fas-associated protein with death domain (FADD) has been implicated in T lymphocytes, but the nature of FADD-dependent mechanism in early T cell development has not been completely elucidated. In this study, using T-cell specific deletion mice, we observed that FADD deficiency in thymocytes led to increased apoptosis and reduced cell numbers, which may be attributed to the reduction of Glut1 expression and correspondingly decreased glucose uptake. Furthermore, an abnormal transduction of Akt signaling was discovered in FADD(-/-) thymocytes, which may be responsible for the declined Glut1 expression. Collectively, our results demonstrate the new function of FADD in glucose metabolism and survival of early T cells.

[Progress on PI3K/Akt signaling pathway regulating self-renewal and pluripotency of embryonic stem cells].

The phosphatidylinositol 3-kinase (PI3K) and its downstream target protein kinase B (Akt/PKB) can be activated by a variety of extracellular and intracellular signals. They are important signaling molecules and key survival factors involved in cell proliferation, differentiation, apoptosis and other cellular processes. Recently, many reports demonstrate that type I PI3K/Akt signaling pathway plays an important role in maintenance of self-renewal and pluripotency of embryonic stem (ES) cells. Further studies with regard to the self-renewal and pluripotency of ES cells and underlying molecular mechanisms are crucial to its application in cell replacement therapy, regenerative medicine and tissue engineering. The present review focuses on the recent progress on the mediation of PI3K/Akt signaling pathway on the maintenance of self-renewal and pluripotency of ES cells.

Therapeutic potential of cannabidiol (CBD) in anxiety disorders: A systematic review and meta-analysis.

Cannabidiol (CBD), as one of the phytocannabinoids, has a wide range of therapeutic properties for various neuropsychiatric disorders due to central nervous system effects. These therapeutic properties demonstrated by preclinical and clinical studies encompass more than just anticonvulsant, anti-arthritic, analgesic, anti-inflammatory, antioxidant, antitumor, antiemetic, antipsychotic and neuroprotective effects. It has been hypothesized that CBD holds potential in the treatment of various neuropsychiatric and anxiety disorders. Thus, PRISMA was used as a guide for our systematic review. Eight of the 1550 articles screened in June 2023 were eligible for meta-analysis. Based on the 316 participants included in these eight articles, this meta-analysis revealed a substantial significant impact of CBD on anxiety with a considerable effect size (Hedges' g = -0.92, 95% CI -1.80 to -0.04). In addition, this meta-analysis focuses on the efficacy of CBD in treating anxiety disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD). However, caution should be exercised in interpreting our findings due to the limited size of the clinical sample, and additional trials ought to be carried out if deemed necessary.

Inducement mechanism and control of self-acidification in elemental sulfur fluidizing bioreactor.

The sulfur fluidizing bioreactor (S0FB) has significant superiorities in treating nitrate-rich wastewater. However, substantial self-acidification has been observed in engineering applications, resulting in frequent start-up failures. In this study, self-acidification was reproduced in a lab-scale S0FB. It was demonstrated that self-acidification was mainly induced by sulfur disproportionation process, accounting for 93.4 % of proton generation. Supplying sufficient alkalinity to both the influent (3000 mg/L) and the bulk (2000 mg/L) of S0FB was essential for achieving a successful start-up. Furthermore, the S0FB reached 10.3 kg-N/m3/d of nitrogen removal rate and 0.13 kg-PO43-/m3/d of phosphate removal rate, respectively, surpassing those of the documented sulfur packing bioreactors by 7-129 times and 26-65 times. This study offers a feasible and practical method to avoid self-acidification during restart of S0FB and highlights the considerable potential of S0FB in the treatment of nitrate-rich wastewater.