Analysis of chloroplast genome characteristics and codon usage bias in 14 species of Annonaceae.

For the study of species evolution, chloroplast gene expression, and transformation, the chloroplast genome is an invaluable resource. Codon usage bias (CUB) analysis is a tool that is utilized to improve gene expression and investigate evolutionary connections in genetic transformation. In this study, we analysed chloroplast genome differences, codon usage patterns and the sources of variation on CUB in 14 Annonaceae species using bioinformatics tools. The study showed that there was a significant variation in both gene sizes and numbers between the 14 species, but conservation was still maintained. It's worth noting that there were noticeable differences in the IR/SC sector boundary and the types of SSRs among the 14 species. The mono-nucleotide repeat type was the most common, with A/T repeats being more prevalent than G/C repeats. Among the different types of repeats, forward and palindromic repeats were the most abundant, followed by reverse repeats, and complement repeats were relatively rare. Codon composition analysis revealed that all 14 species had a frequency of GC lower than 50%. Additionally, it was observed that the proteins in-coding sequences of chloroplast genes tend to end with A/T at the third codon position. Among these species, 21 codons exhibited bias (RSCU > 1), and there were 8 high-frequency (HF) codons and 5 optimal codons that were identical across the species. According to the ENC-plot and Neutrality plot analysis, natural selection had less impact on the CUB of A. muricate and A. reticulata. Based on the PR2-plot, it was evident that base G had a higher frequency than C, and T had a higher frequency A. The correspondence analysis (COA) revealed that codon usage patterns different in Annonaceae.

New Cocrystals of Ligustrazine: Enhancing Hygroscopicity and Stability.

Ligustrazine (TMP) is the main active ingredient extracted from Rhizoma Chuanxiong, which is used in the treatment of cardiovascular and cerebrovascular diseases, with the drawback of being unstable and readily sublimated. Cocrystal technology is an effective method to improve the stability of TMP. Three benzoic acid compounds including P-aminobenzoic acid (PABA), 3-Aminobenzoic acid (MABA), and 3,5-Dinitrobenzoic acid (DNBA) were chosen for co-crystallization with TMP. Three novel cocrystals were obtained, including TMP-PABA (1:2), TMP-MABA (1.5:1), and TMP-DNBA (0.5:1). Hygroscopicity was characterized by the dynamic vapor sorption (DVS) method. Three cocrystals significantly improved the hygroscopicity stability, and the mass change in TMP decreased from 25% to 1.64% (TMP-PABA), 0.12% (TMP-MABA), and 0.03% (TMP-DNBA) at 90% relative humidity. The melting points of the three cocrystals were all higher than TMP, among which the TMP-DNBA cocrystal had the highest melting point and showed the best stability in reducing hygroscopicity. Crystal structure analysis shows that the mesh-like structure formed by the O-H⋯N hydrogen bond in the TMP-DNBA cocrystal was the reason for improving the stability of TMP.

A Novel Cocrystal of Daidzein with Piperazine to Optimize the Solubility, Permeability and Bioavailability of Daidzein.

It is well known that daidzein has various significant medicinal values and health benefits, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, cholesterol lowering, neuroprotective, cardioprotective and so on. To our disappointment, poor solubility, low permeability and inferior bioavailability seriously limit its clinical application and market development. To optimize the solubility, permeability and bioavailability of daidzein, the cocrystal of daidzein and piperazine was prepared through a scientific and reasonable design, which was thoroughly characterized by single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Combining single-crystal X-ray diffraction analysis with theoretical calculation, detailed structural information on the cocrystal was clarified and validated. In addition, a series of evaluations on the pharmacogenetic properties of the cocrystal were investigated. The results indicated that the cocrystal of daidzein and piperazine possessed the favorable stability, increased solubility, improved permeability and optimized bioavailability of daidzein. Compared with the parent drug, the formation of cocrystal, respectively, resulted in 3.9-, 3.1-, 4.9- and 60.8-fold enhancement in the solubility in four different media, 4.8-fold elevation in the permeability and 3.2-fold in the bioavailability of daidzein. Targeting the pharmaceutical defects of daidzein, the surprising elevation in the solubility, permeability and bioavailability of daidzein was realized by a clever cocrystal strategy, which not only devoted assistance to the market development and clinical application of daidzein but also paved a new path to address the drug-forming defects of insoluble drugs.

Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure.

Heart failure (HF) is a clinical syndrome of cardiac insufficiency caused by abnormalities in cardiac structure and function that arise for various reasons, and it is the final stage of most cardiovascular diseases' progression. Total flavonoid extract from Dracocephalum moldavica L. (TFDM) has many pharmacological and biological roles, such as cardioprotective, neuroprotective, anti-atherogenic, antihypertensive, anti-diabetic, anti-inflammatory, antioxidant, etc. However, its effect on HF and its molecular mechanism are still unclear. In this study, we used systems pharmacology and an animal model of HF to investigate the cardioprotective effect of TFDM and its molecular mechanism. Eleven compounds in TFDM were obtained from the literature, and 114 overlapping genes related to TFDM and HF were collected from several databases. A PPI network and C-T network were established, and GO enrichment analysis and KEGG pathway analysis were performed. The top targets from the PPI network and C-T network were validated using molecular docking. The pharmacological activity was investigated in an HFpEF (heart failure with preserved ejection fraction) mouse model. This study shows that TFDM has a protective effect on HFpEF, and its protective mechanism may be related to the regulation of proinflammatory cytokines, apoptosis-related genes, fibrosis-related genes, etc. Collectively, this study offers new insights for researchers to understand the protective effect and mechanism of TFDM against HFpEF using a network pharmacology method and a murine model of HFpEF, which suggest that TFDM is a promising therapy for HFpEF in the clinic.

Cocrystals of Praziquantel with Phenolic Acids: Discovery, Characterization, and Evaluation.

Solvent-assisted grinding (SAG) and solution slow evaporation (SSE) methods are generally used for the preparation of cocrystals. However, even by using the same solvent, active pharmaceutical ingredient (API), and cocrystal coformer (CCF), the cocrystals prepared using the two methods above are sometimes inconsistent. In the present study, in the cocrystal synthesis of praziquantel (PRA) with polyhydroxy phenolic acid, including protocatechuic acid (PA), gallic acid (GA), and ferulic acid (FA), five different cocrystals were prepared using SAG and SSE. Three of the cocrystals prepared using the SAG method have the structural characteristics of carboxylic acid dimer, and two cocrystals prepared using the SSE method formed cocrystal solvates with the structural characteristics of carboxylic acid monomer. For phenolic acids containing only one phenolic hydroxyl group (ferulic acid), when preparing cocrystals with PRA by using SAG and SSE, the same product was obtained. In addition, the weak molecular interactions that were observed in the cocrystal are explained at the molecular level by using theoretical calculation methods. Finally, the in vitro solubility of cocrystals without crystal solvents and in vivo bioavailability of PRA-FA were evaluated to further understand the influence on the physicochemical properties of API for the introduction of CCF.

Recent Advances on the Biological Study of Pharmaceutical Cocrystals.

As a low-risk, low-cost, but high-reward route, cocrystallization of drugs with appropriate coformers is applied to improve the physiochemical and biopharmaceutical properties of drugs. Currently, most researchers concentrate their efforts on the preparation, characterization, and improvement of physicochemical properties of pharmaceutical cocrystals. On the contrary, the biological study of pharmaceutical cocrystals has not attracted wide attention of researchers. In this review, we have focused on recent advances reporting the biological studies of pharmaceutical cocrystals. The covered areas consist of the solubility and permeability, the pharmacokinetics study, metabolism and distribution, pharmacodynamics research, and the toxicological evaluation of pharmaceutical cocrystals. Besides, discussions have been made on the in vivo-in vitro correlations for pharmaceutical cocrystals, the enhancement of efficiency and reduction of toxicity for pharmaceutical cocrystals, and the interaction between APIs and coformers in pharmaceutical cocrystals and marketed pharmaceutical cocrystals as well as their biological studies. At the same time, some problems such as the amount of animal samples, the number and distribution of blood sampling points, investigation on the pharmacokinetics of physical mixtures containing APIs and coformers, and the consideration of species differences should be taken into account. Although pharmaceutical cocrystals face some challenges in clarifying the characteristics of metabolism and distribution, revealing potential pharmacological mechanism, and evaluating safety, cocrystal engineering is still considered a green and promising approach to developing valuable new drugs.

Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study.

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Vitellogenin from planthopper oral secretion acts as a novel effector to impair plant defenses.

Vitellogenin (Vg) is a well-known nutritious protein involved in reproduction in nearly all oviparous animals, including insects. Recently, Vg has been detected in saliva proteomes of several piercing-sucking herbivorous arthropods, including the small brown planthopper (Laodelphax striatellus, SBPH). Its function, however, remains unexplored. We investigated the molecular mechanism underlying SBPH orally secreted Vg-mediated manipulation of plant-insect interaction by RNA interference, phytohormone and H2 O2 profiling, protein-protein interaction studies and herbivore bioassays. A C-terminal polypeptide of Vg (VgC) in SBPH, when secreted into rice plants, acted as a novel effector to attenuate host rice defenses, which in turn improved insect feeding performance. Silencing Vg reduced insect feeding and survival on rice. Vg-silenced SBPH nymphs consistently elicited higher H2 O2 production, a well-established defense mechanism in rice, whereas expression of VgC in planta significantly hindered hydrogen peroxide (H2 O2 ) accumulation and promoted insect performance. VgC interacted directly with the rice transcription factor OsWRKY71, a protein which is involved in induction of H2 O2 accumulation and plant resistance to SBPH. These findings indicate a novel effector function of Vg: when secreted into host rice plants, this protein effectively weakened H2 O2 -mediated plant defense through its association with a plant immunity regulator.

Role of Artesunate on cardiovascular complications in rats with type 1 diabetes mellitus.

BACKGROUND: The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway. METHODS: A total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR. RESULTS: The results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05). CONCLUSIONS: ART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.

Incidence and Risk Factors of Moderate to Severe Postoperative Pain Following the Placement of Primary and Secondary Orbital Implants: A Prospective Observational Study.

PURPOSE: To prospectively explore the incidence and risk factors of moderate to severe pain after primary and secondary orbital implantation following evisceration or enucleation surgery. METHODS: One hundred eighteen patients under general anesthesia for orbital implantation were enrolled in this study. In 91 patients, primary orbital implantation followed evisceration, and in 27 patients, the implantation was secondary after previous evisceration or enucleation surgery. Medical interventions for all participants were followed by standardized surgical, anesthetic, and analgesic protocols. Postoperative pain (POP) intensity was quantified by an 11-point numerical rating scale within 72 hours after the surgery, numerical rating scale ≥4 was considered moderate to severe POP. Multivariate logistic regression was utilized to identify the risk factors related to the development of POP. RESULTS: Thirty-five patients (29.7%) displayed moderate to severe POP, particularly within 6 to 24 hours after surgery, which peaked at 24 hours. Of these patients, 26 patients who were unable to tolerate the pain received additional doses of analgesics during in-hospital stay. Logistic regression model revealed that preoperative anxiety (odds ratios = 4.890; p = 0.002), congenital microphthalmia (odds ratios = 14.602; p = 0.038), and surgical time longer than 60 minutes (odds ratios = 5.586; p = 0.001) were significantly associated with moderate to severe POP after orbital implantation. CONCLUSIONS: Orbital implantation after evisceration or enucleation surgery is likely to cause moderate to severe pain intensity in the early postoperative period. Preoperative anxiety, prolonged surgical time, and congenital microphthalmia were the risk factors.

Cocrystal of Apixaban-Quercetin: Improving Solubility and Bioavailability of Drug Combination of Two Poorly Soluble Drugs.

Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx-Que (1:1) and Apx-Que-2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx-Que-2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx-Que was increased compared with the physical mixture and Apx, and Apx-Que remained stable in high temperature and illumination conditions. Therefore, a drug-drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.

Using Clinical-Based Discharge Criteria to Discharge Patients After Ophthalmic Ambulatory Surgery Under General Anesthesia: An Observational Study.

PURPOSE: To verify the feasibility of the clinical-based discharge (CBD) criteria and identify the reasons of long postanesthesia care unit length of stay (PACU-LOS) for ophthalmic ambulatory surgical patients under general anesthesia. DESIGN: A prospectively observational study conducted at a tertiary eye center in China. METHODS: Medical records were collected from patients admitted for strabismus ambulatory surgery under general anesthesia from September 2018 to March 2019. The patients were discharged home once met the CBD criteria based on a combination of the modified Aldrete's scoring system and Chung's Post-Anesthetic Discharge Scoring System. Postoperative complications were recorded in the PACU and within 24 hours after discharge. Multivariate logistic regression was applied to identify the factors relating to late discharges. FINDINGS: All patients (N = 400) were safely and successfully same-day discharged home as none of the patients informed severe emergency events or unanticipated readmission. Nine displayed discharge delays mainly because of mild postoperative nausea and vomiting (PONV) although met the discharge criteria. About 85.5% of patients were discharged within a PACU-LOS of 150 minutes, 379 (94.8%) were within 180 minutes, and the cutoff time in PACU-LOS was 150 minutes. Multivariable analysis indicated that sevoflurane anesthesia and the presence of PONV were related to late discharges (PACU-LOS of greater than 150 minutes, all P < .05). CONCLUSIONS: The CBD criteria can efficiently and safely guide the ophthalmic ambulatory surgical patients to discharge home on the same-surgery day, whereas sevoflurane anesthesia and the presence of PONV are associated with a relatively long PACU-LOS.

Nrf2- and Bach1 May Play a Role in the Modulation of Ultraviolet A-Induced Oxidative Stress by Acetyl-11-Keto-ß-Boswellic Acid in Skin Keratinocytes.

BACKGROUND: Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis. OBJECTIVE: The aim of this study is to investigate the protective effect of acetyl-11-keto-ß-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes. METHODS: HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined. RESULTS: AKBA reduces UVA irradiation-induced cell viability loss, accompanied by a decreased production of UVA-induced ROS, decreased malondialdehyde, and increased superoxide dismutase expression. In addition, AKBA increased basal and UVA-induced levels of Nrf2 (NF-E2-related factor 2), the redox-sensitive factor, and its target genes NQO1 and heme oxygenase-1 (HO-1), whereas expression of the transcriptional repressor Bach1 (BTB and CNC homology 1) was reduced. Furthermore, the cytoprotective effects of AKBA against UVA-derived oxidative damage were accompanied by modulating expression of inflammatory mediators (i.e., cyclooxygenase-2 and nuclear factor-κB) and NOX1. CONCLUSIONS: AKBA protects skin cells from UVA-induced damage by modulating inflammatory mediators and/or ROS production. Therefore, AKBA has potential in the development of skin care products.

Characteristics of extracellular polymeric substances from sludge and biofilm in a simultaneous nitrification and denitrification system under high salinity stress.

The composition and distribution of extracellular polymeric substance (EPS) both from suspended sludge and attached biofilm were investigated in a simultaneous nitrification and denitrification (SND) system with the increase of the salinity from 1.0 to 3.0 %. Fourier-transform infrared (FTIR) spectroscopy and three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy were used to examine proteins (PN), polysaccharides (PS) and humic substances (HS) present in EPS. High total nitrogen removal (above 83.9 %) via SND was obtained in the salinity range of 1.0-2.5 %. Total EPS in the sludge increased from 150.2 to 200.6 mg/gVSS with the increase of salinity from 1.0 to 3.0 %, whereas the corresponding values in the biofilm achieved the maximum of 288.6 mg/g VSS at 2.0 % salinity. Dominant composition of EPS was detected as HS in both sludge and biofilm, having the percentages of 50.6-68.6 and 41.1-69.9 % in total EPS, respectively. Both PN and PS contents in soluble EPS (S-EPS), loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) of sludge and biofilm increased with the increased salinity. The FTIR spectrum and 3D-EEM fluorescence spectroscopy of S-EPS, LB-EPS and TB-EPS in the sludge and biofilm showed the changes of functional groups and conformations of the compositions in EPS with the increase of salinity. The results demonstrated that the characteristics of EPS varied from sludge to biofilm. The obtained results could provide a better understanding of the salinity effect on the EPS characteristics in a SND system.

[Research on certified reference material of emodin in rhubarb and its alcohol extract, water extract].

The certified reference materials (CRMs) of emodin in rhubarb and its alcohol extract, water extract were developed by using quantity transfer technology from single chemical composition to the complex systems. The CRM of emodin was used for quantity transfer, and high performance liquid chromatography (HPLC) method was used to determine the contents of emodin in different matrix composition. By establishing mathematical model and calculating the parts of uncertainty, the uncertainty values were finally gotten. CRMs of emodin in rhubarb, alcohol extract and water extract were accomplished. The content values of emodin were 0.40% ±0.03%, 1.15%±0.18%, 0.16%±0.08% (k=2,P=0.95), respectively. The established method for quantity transfer has successfully solved the technical problems that the value of active ingredient of traditional Chinese medicine can't be traced to SI units. The series of CRMs are assigned as grade primary reference materials, which are useful for quality control of the emodin content, also provide the accurate and reliable CRM, materials standard and standard methods.

Certification of a new certified reference material of honokiol.

Honokiol is the most important active pharmaceutical ingredient in Magnolia officinalis, which is a famous traditional Chinese medicine and commonly used in clinical practice. In order to control the quality of honokiol and related pharmaceuticals, a new certified reference material (CRM) of honokiol was developed. The studies of sample preparation, homogeneity, stability, value assignment, and uncertainty evaluation were accomplished in this paper. Three different methods, including differential scanning calorimetry (DSC), mass balance method (MB), and coulometric titration (CT), were employed to determine the purity of honokiol. Specifically, the DSC and CT methods for purity determination of honokiol were established for the first time. The purity of honokiol CRM, after validation and evaluation, was found to be 99.3%, with an expanded uncertainty of 0.5% (k = 2).

Rapid and simple spectrophotometric determination of persulfate in water by microwave assisted decolorization of Methylene Blue.

A rapid and simple method for determination of persulfate in aqueous solution was developed. The method is based on the rapid reaction of persulfate with Methylene Blue (MB) via domestic microwave activation, which can promote the activation of persulfate and decolorize MB quickly. The depletion of MB at 644 nm (the maximum absorption wavelength of MB) is in proportion to the increasing concentration of persulfate in aqueous solution. Linear calibration curve was obtained in the range 0-1.5 mmol/L, with a limit of detection of 0.0028 mmol/L. The reaction time is rapid (within 60 sec), which is much shorter than that used for conventional methods. Compared with existing analytical methods, it need not any additives, especially colorful Fe2+, and need not any pretreatment for samples, such as pH adjustment.

Impact of Bullying Victimization on Chinese College Students' Suicidal Tendency: The Moderating Effect of Teachers' Emotional Support and Family Support.

Objective: To explore the influence of bully victims on the suicidal tendencies of college students, and the moderating role of teacher emotional support and family support in the relationship between bully victims and college students' suicidal tendencies, in order to provide a reference for the effective intervention of college students' suicide behavior. Methods: Based on a survey of 15,560 college students. Multiple stepwise regression and Interaction analysis explore the impact of the bully victimization on college students' suicidal tendencies and the moderating role of family support and teacher emotional support in the relationship between the bully victim and college students' suicidal tendencies. Results: This study found that the Suicidal Tendencies score of college students was 19.79 points, indicating that some college students have a risk of suicidal tendencies; secondly, verbal bullying (ß = 0.084, P <0.001), physical bullying (ß = 0.222, P <0.001) and social relationship bullying (ß = 0.122, P <0.001) have a positive and significant impact on the suicidal tendencies of college students; in addition, family support and teacher emotional support have a significant regulatory effect on the bully victim and college students Suicidal Tendencies and family support. The regulating effect was significantly higher than that of teacher emotional support. Conclusion: Chinese college students have the risk of suicidal tendencies; peer bullying victimization is an important reason for affecting college students' suicidal tendencies, teacher emotional support is a protective factor for bully victims to affect college students' suicidal tendencies, and family support has a significant moderating effect on the bully victim and college students' suicidal tendencies. Therefore, it is necessary to actively adopt home-school linkage and home-school communication to reduce campus violence and increase the psychological resilience of college students.

Current advances on the therapeutic potential of scutellarin: an updated review.

Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed.

Metformin-Mediated Improvement in Solubility, Stability, and Permeability of Nonsteroidal Anti-Inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are class II biopharmaceutics classification system drugs. The poor aqueous solubility of NSAIDs can lead to limited bioavailability after oral administration. Metformin (MET), a small-molecule compound, can be used in crystal engineering to modulate the physicochemical properties of drugs and to improve the bioavailability of orally administered drugs, according to the literature research and preliminary studies. We synthesized two drug-drug molecular salts (ketoprofen-metformin and phenylbutazone-metformin) with NSAIDs and thoroughly characterized them using SCXRD, PXRD, DSC, and IR analysis to improve the poor solubility of NSAIDs. In vitro evaluation studies revealed that the thermal stability and solubility of NSAIDs-MET were substantially enhanced compared with those of NSAIDs alone. Unexpectedly, an additional increase in permeability was observed. Since the structure determines the properties, the structure was analyzed using theoretical calculations to reveal the intermolecular interactions and to explain the reason for the change in properties. The salt formation of NSAIDs with MET could substantially increase the bio-absorption rate of NSAIDs, according to the in vivo pharmacokinetic findings, which provides an experimental basis for developing new antipyretic and analgesic drugs with rapid onset of action.