FMNL2 regulates actin for endoplasmic reticulum and mitochondria distribution in oocyte meiosis.

During mammalian oocyte meiosis, spindle migration and asymmetric cytokinesis are unique steps for the successful polar body extrusion. The asymmetry defects of oocytes will lead to the failure of fertilization and embryo implantation. In present study, we reported that an actin nucleating factor Formin-like 2 (FMNL2) played critical roles in the regulation of spindle migration and organelle distribution in mouse and porcine oocytes. Our results showed that FMNL2 mainly localized at the oocyte cortex and periphery of spindle. Depletion of FMNL2 led to the failure of polar body extrusion and large polar bodies in oocytes. Live-cell imaging revealed that the spindle failed to migrate to the oocyte cortex, which caused polar body formation defects, and this might be due to the decreased polymerization of cytoplasmic actin by FMNL2 depletion in the oocytes of both mice and pigs. Furthermore, mass spectrometry analysis indicated that FMNL2 was associated with mitochondria and endoplasmic reticulum (ER)-related proteins, and FMNL2 depletion disrupted the function and distribution of mitochondria and ER, showing with decreased mitochondrial membrane potential and the occurrence of ER stress. Microinjecting Fmnl2-EGFP mRNA into FMNL2-depleted oocytes significantly rescued these defects. Thus, our results indicate that FMNL2 is essential for the actin assembly, which further involves into meiotic spindle migration and ER/mitochondria functions in mammalian oocytes.

The influence of water safety knowledge on adolescents' drowning risk behaviors: a framework of risk-protect integrated and KAP theory.

Introduction: Although previous research has examined the risk factors for drowning behavior among adolescents, it is unclear whether this association is influenced by water safety knowledge. This study aimed to examine whether water safety knowledge is associated with adolescents' drowning risk behaviors and whether drowning risk perceptions and attitudes could have a chain mediating role in the association between water safety knowledge and adolescents' drowning risk behaviors. Methods: This study included 7,485 adolescents from five Chinese provinces and cities. We used the Drowning Risk Behaviors Scales (DRBS) to evaluate the risk of drowning behaviors. The Water Safety Knowledge Scale (WSKS) was used to evaluate the competence level of water safety knowledge. The Drowning Risk Perceptions Scale (DRPS) was used to evaluate the risk level of perceptions, and the Drowning Risk Attitudes Scale (DRAS) was used to evaluate the risk level of attitudes. Results: The results of the mediating effect test showed that water safety knowledge (WSK) affected drowning risk behaviors (DRB) through three indirect paths. Drowning risk perceptions (DRP) and attitudes (DRA) have significantly mediated the association between WSK and DRB. In conclusion, DRP and DRA can act as mediators between WSK and DRB, not only individually, but also as chain mediators, where the direct effect is-0.301, the total indirect effect is-0.214, and the total mediated indirect effect is 41.5%. Discussion: Water safety knowledge negatively predicts adolescents' drowning risk behaviors; water safety knowledge has an inhibitory effect on drowning risk perceptions. Water safety knowledge can directly influence adolescents' drowning risk perceptions and indirectly affect drowning risk behaviors through the mediation of drowning risk perceptions and attitudes comprising three paths: (1) the drowning risk perceptions mediation path, (2) the drowning risk attitudes mediation path, and (3) the drowning risk perceptions and attitudes mediation paths.

A Single Latent Plant Growth-Promoting Endophyte BH46 Enhances Houttuynia cordata Thunb. Yield and Quality.

Plant growth-promoting endophytes (PGPE) can effectively regulate plant growth and metabolism. The regulation is modulated by metabolic signals, and the resulting metabolites can have considerable effects on the plant yield and quality. Here, tissue culture Houttuynia cordata Thunb., was inoculated with Rhizobium sp. (BH46) to determine the effect of BH46 on H. cordata growth and metabolism, and elucidate associated regulatory mechanisms. The results revealed that BH46 metabolized indole-3-acetic acid and induced 1-aminocyclopropane-1-carboxylate deaminase to decrease ethylene metabolism. Host peroxidase synthesis MPK3/MPK6 genes were significantly downregulated, whereas eight genes associated with auxins, cytokinins, abscisic acid, jasmonic acid, and antioxidant enzymes were significantly upregulated. Eight genes associated with flavonoid biosynthesis were significantly upregulated, with the CPY75B1 gene regulating the production of rutin and quercitrin and the HCT gene directly regulating the production of chlorogenic acid. Therefore, BH46 influences metabolic signals in H. cordata to modulate its growth and metabolism, in turn, enhancing yield and quality of H. cordata.

Electrically Oriented Antibodies on Transistor for Monitoring Several Copies of Methylated DNA.

An antibody transistor is a promising biosensing platform for the diagnosis and monitoring of various diseases. Nevertheless, the low concentration and short half-life of biomarkers require biodetection at the trace-molecule level, which remains a challenge for existing antibody transistors. Herein, we demonstrate a graphene field-effect transistor (gFET) with electrically oriented antibody probes (EOA-gFET) for monitoring several copies of methylated DNA. The electric field confines the orientation of antibody probes on graphene and diminishes the distance between graphene and methylated DNAs captured by antibodies, generating more induced charges on graphene and amplifying the electric signal. EOA-gFET realizes a limit of detection (LoD) of ∼0.12 copy µL-1, reaching the lowest LoD reported before. EOA-gFET shows a distinguishable signal for liver cancer clinical serum samples within ∼6 min, which proves its potential as a powerful tool for disease screening and diagnosis.

Artificial Tactile Receptor System for Sensitive Pressure-Neural Spike Conversion.

An artificial tactile receptor is crucial for e-skin in next-generation robots, mimicking the mechanical sensing, signal encoding, and preprocessing functionalities of human skin. In the neural network, pressure signals are encoded in spike patterns and efficiently transmitted, exhibiting low power consumption and robust tolerance for bit error rates. Here, we introduce a highly sensitive artificial tactile receptor system integrating a pressure sensor, axon-hillock circuit, and neurotransmitter release device to achieve pressure signal coding with patterned spikes and controlled neurotransmitter release. Owing to the heightened sensitivity of the axon-hillock circuit to pressure-mediated current signals, the artificial tactile receptor achieves a detection limit of 10 Pa that surpasses the human tactile receptors, with a wide response range from 10 to 5 × 105 Pa. Benefiting from the appreciable pressure-responsive performance, the potential application of an artificial tactile receptor in robotic tactile perception has been demonstrated, encompassing tasks such as finger touch and human pulse detection.

Nematicidal Activity of 20-Deoxyingenol-3-angelate from Euphorbia peplus Latex Through Protein Kinase C Isotype TPA-1.

The latex of Euphorbia peplus and its major component 20-deoxyingenol-3-angelate (DI3A) displayed significant nematicidal activity against Caenorhabditis elegans and Panagrellus redivivus. DI3A treatment inhibited the growth and development of nematodes and caused significantly negative effects on locomotion behavior, reproduction, and accumulation of reactive oxygen species. Transcriptome analysis indicated that differential expression genes in DI3A-treated C. elegans were mainly associated with the metabolism, growth, and development process, which were further confirmed by RT-qPCR experiments. The expression level of TPA-1 gene encoding a protein kinase C isotype was obviously upregulated by DI3A treatment, and knockdown of TPA-1 by RNAi technology in the nematode could relieve the growth-inhibitory effect of DI3A. Metabolic analysis indicated that DI3A was hardly metabolized by C. elegans, but a glycosylated indole derivative was specifically accumulated likely due to the activation of detoxification. Overall, our findings suggested that DI3A from E. peplus latex exerted a potent nematicidal effect through the gene TPA-1, which provides a potential target for the control of nematodes and also suggests the potential application value of E. peplus latex and DI3A as botanical nematicides.

[Cases Analysis of Hemoglobin H Disease Caused by HBA2:c.2T>C and HBA2:c.2delT Mutations].

OBJECTIVE: To investigate two cases of rare pathogenic genes, initiation codon mutations in HBA2 gene, combined with Southeast Asian deletion and their family members to understand the relationship of HBA2:c.2T>C and HBA2:c.2delT mutations with clinical phenotype. METHODS: The peripheral blood of family members was obtained for blood cell analysis and capillary electrophoresis hemoglobin analysis. Gap-PCR and reverse dot blotting (RDB) were used to detect common types of mutations in ɑ-thalassaemia gene. Sanger sequencing was used to analyze HBA1 and HBA2 gene sequence. RESULTS: Two proband genotypes were identified as --SEA/αα with HBA2:c.2T>C and --SEA/αα with HBA2:c.2delT. HBA2:c.2T>C/WT and HBA2:c.2delT/WT was detected in family members. They all presented with microcytic hypochromic anemia. CONCLUSION: When HBA2:c.2T>C and HBA2:c.2delT are heterozygous that can lead to static α-thalassemia phenotype, and when combined with mild α-thalassemia, they can lead to the clinical manifestations of hemoglobin H disease. This study provides a basis for genetic counseling.

The Effectiveness of Interventions for Reducing Loneliness Among Chinese Older Adults: A Systematic Review and Meta-Analysis.

This review assesses interventions to reduce loneliness in Chinese older adults, analyzing 36 studies involving 3965 participants. Focusing on individuals aged 50 and over, the meta-analysis reveals a significant overall effect size (Hedges' g = 0.937, 95% CI [0.71,1.16], p<0.001), highlighting the effectiveness of psychological and mixed-method approaches. Despite promising results, methodological concerns suggest cautious interpretation. Future research should aim to refine intervention quality and examine the impact of technology-supported methods on loneliness.

Phosphorylation-regulated phase separation of syndecan-4 and syntenin promotes the biogenesis of exosomes.

The biogenesis of exosomes that mediate cell-to-cell communication by transporting numerous biomolecules to neighbouring cells is an essential cellular process. The interaction between the transmembrane protein syndecan-4 (SDC4) and cytosolic protein syntenin plays a key role in the biogenesis of exosomes. However, how the relatively weak binding of syntenin to SDC4 efficiently enables syntenin sorting for packaging into exosomes remains unclear. Here, we demonstrate for the first time that SDC4 can undergo liquid-liquid phase separation (LLPS) to form condensates both in vitro and in the cell membrane and that, the SDC4 cytoplasmic domain (SDC4-CD) is a key contributor to this process. The phase separation of SDC4 greatly enhances the recruitment of syntenin to the plasma membrane (PM) despite the weak SDC4-syntenin interaction, facilitating syntenin sorting for inclusion in exosomes. Interestingly, phosphorylation at the only serine (179) in the SDC4-CD (Ser179) disrupts SDC4 LLPS, and inhibited phosphorylation or dephosphorylation restores the SDC4 LLPS to promote its recruitment of syntenin to the PM and syntenin inclusion into exosomes. This research reveals a novel phosphorylation-regulated phase separation property of SDC4 in the PM through which SDC4 efficiently recruits cytosolic syntenin and facilitates the biogenesis of exosomes, providing potential intervention targets for exosome-mediated biomedical events.

Ligation of cervical lymphatic vessels decelerates blood clearance and worsens outcomes after experimental subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is characterized by the extravasation of blood into the subarachnoid space, in which erythrocyte lysis is the primary contributor to cell death and brain injuries. New evidence has indicated that meningeal lymphatic vessels (mLVs) are essential in guiding fluid and macromolecular waste from cerebrospinal fluid (CSF) into deep cervical lymph nodes (dCLNs). However, the role of mLVs in clearing erythrocytes after SAH has not been completely elucidated. Hence, we conducted a cross-species study. Autologous blood was injected into the subarachnoid space of rabbits and rats to induce SAH. Erythrocytes in the CSF were measured with/without deep cervical lymph vessels (dCLVs) ligation. Additionally, prior to inducing SAH, we administered rats with vascular endothelial growth factor C (VEGF-C), which is essential for meningeal lymphangiogenesis and maintaining integrity and survival of lymphatic vessels. The results showed that the blood clearance rate was significantly lower after dCLVs ligation in both the rat and rabbit models. DCLVs ligation aggravated neuroinflammation, neuronal damage, brain edema, and behavioral impairment after SAH. Conversely, the treatment of VEGF-C enhanced meningeal lymphatic drainage of erythrocytes and improved outcomes in SAH. In summary, our research highlights the indispensable role of the meningeal lymphatic pathway in the clearance of blood and mediating consequences after SAH.

Rapid and Mechanically Robust Immobilization of Proteins on Silica Studied at the Single-Molecule Level by Force Spectroscopy and Verified at the Macroscopic Level.

Typical methods for stable immobilization of proteins often involve time-consuming surface modification of silicon-based materials to enable specific binding, while the nonspecific adsorption method is faster but usually unstable. Herein, we fused a silica-binding protein, Si-tag, to target proteins so that the target proteins could attach directly to silica substrates in a single step, markedly streamlining the immobilization process. The adhesion force between the Si-tag and glass substrates was determined to be approximately 400-600 pN at the single-molecule level by atomic force microscopy, which is greater than the unfolding force of most proteins. The adhesion force of the Si-tag exhibits a slight increase when pulled from the C-terminus compared to that from the N-terminus. Furthermore, the Si-tag's adhesion force on a glass surface is marginally higher than that on a silicon nitride probe. The binding properties of the Si-tag are not obviously affected by environmental factors, including pH, salt concentration, and temperature. In addition, the macroscopic adhesion force between the Si-tag-coated hydrogel and glass substrates was ∼40 times higher than that of unmodified hydrogels. Therefore, the Si-tag, with its strong silica substrate binding ability, provides a useful tool as an excellent fusion tag for the rapid and mechanically robust immobilization of proteins on silica and for the surface coating of silica-binding materials.

DsbA-L ameliorates renal aging and renal fibrosis by maintaining mitochondrial homeostasis.

Renal fibrosis is the final pathological change in renal disease, and aging is closely related to renal fibrosis. Mitochondrial dysfunction has been reported to play an important role in aging, but the exact mechanism remains unclear. Disulfide-bond A oxidoreductase-like protein (DsbA-L) is mainly located in mitochondria and plays an important role in regulating mitochondrial function and endoplasmic reticulum (ER) stress. However, the role of DsbA-L in renal aging has not been reported. In this study, we showed a reduction in DsbA-L expression, the disruption of mitochondrial function and an increase in fibrosis in the kidneys of 12- and 24-month-old mice compared to young mice. Furthermore, the deterioration of mitochondrial dysfunction and fibrosis were observed in DsbA-L-/- mice with D-gal-induced accelerated aging. Transcriptome analysis revealed a decrease in Flt4 expression and inhibition of the PI3K-AKT signaling pathway in DsbA-L-/- mice compared to control mice. Accelerated renal aging could be alleviated by an AKT agonist (SC79) or a mitochondrial protector (MitoQ) in mice with D-gal-induced aging. In vitro, overexpression of DsbA-L in HK-2 cells restored the expression of Flt4, AKT pathway factors, SP1 and PGC-1α and alleviated mitochondrial damage and cell senescence. These beneficial effects were partially blocked by inhibiting Flt4. Finally, activating the AKT pathway or improving mitochondrial function with chemical reagents could alleviate cell senescence. Our results indicate that the DsbA-L/AKT/PGC-1α signaling pathway could be a therapeutic target for age-related renal fibrosis and is associated with mitochondrial dysfunction.

The disordered protein SERF promotes α-Synuclein aggregation through liquid-liquid phase separation.

The aggregation of α-Synuclein (α-Syn) into amyloid fibrils is the hallmark of Parkinson's disease. Under stress or other pathological conditions, the accumulation of α-Syn oligomers is the main contributor to the cytotoxicity. A potential approach for treating Parkinson's disease involves preventing the accumulation of these α-Syn oligomers. In this study, we present a novel mechanism involving a conserved group of disorderly proteins known as small EDRK-rich factor (SERF), which promotes the aggregation of α-Syn through a cophase separation process. Using diverse methods like confocal microscopy, fluorescence recovery after photobleaching assays, solution-state NMR spectroscopy, and Western blot, we determined that the N-terminal domain of SERF1a plays a role in the interactions that occur during cophase separation. Within these droplets, α-Syn undergoes a gradual transformation from solid condensates to amyloid fibrils, while SERF1a is excluded from the condensates and dissolves into the solution. Notably, in vivo experiments show that SERF1a cophase separation with α-Syn significantly reduces the deposition of α-Syn oligomers and decreases its cellular toxicity under stress. These findings suggest that SERF1a accelerates the conversion of α-Syn from highly toxic oligomers to less toxic fibrils through cophase separation, thereby mitigating the biological damage of α-Syn aggregation.

New triterpenoids from the aerial parts of the Uygur medicine Salvia deserta.

Phytochemical investigation on the aerial parts of Salvia deserta led to the isolation of eight new pentacyclic triterpenoids including three oleanane- (1 - 3) and five ursane-type (4 - 8) triterpenoids, whose structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculation. Weak immunosuppressive potency was observed for compounds 1, 2, and 4 - 8 via inhibiting the secretion of cytokines TNF-α and IL-6 in LPS-induced macrophages RAW264.7 at 20 µM. In addition, compounds 1, 2, and 4 - 6 exhibited moderate protective activity on t-BHP-induced oxidative injury in HepG2 cells.

Advances in biosynthesis of peptide drugs: Technology and industrialization.

Peptide drugs are developed from endogenous or synthetic peptides with specific biological activities. They have advantages of strong target specificity, high efficacy and low toxicity, thus showing great promise in the treatment of many diseases such as cancer, infections, and diabetes. Although an increasing number of peptide drugs have entered market in recent years, the preparation of peptide drug substances is yet a bottleneck problem for their industrial production. Comparing to the chemical synthesis method, peptide biosynthesis has advantages of simple synthesis, low cost, and low contamination. Therefore, the biosynthesis technology of peptide drugs has been widely used for manufacturing. Herein, we reviewed the development of peptide drugs and recent advances in peptide biosynthesis technology, in order to shed a light to the prospect of industrial production of peptide drugs based on biosynthesis technology.

Leucosceptrane Sesterterpenoids as a New Type of Natural Immunosuppressive Agents in Treating Sepsis.

Intragastric administration of the total sesterterpenoid extract (TSE) of medicinal plant Leucosceptrum canum at 2.5 g/kg dose protected mice from LPS-induced sepsis. Phytochemical investigation led to the isolation and identification of 47 leucosceptrane sesterterpenoids (1-47) including 30 new compounds (1-30) with complicated oxygenation patterns. Biological screening indicated their immunosuppressive activity via inhibiting IFN-γ secretion and/or proliferation of T cells with different potencies. Mechanism study of compounds 9, 25, and 32 revealed that they inhibited the activations of AKT-mTOR, JNK, p38 MAPK or ERK pathway in T cells and macrophages. In addition, compounds 9 and 25 induced G0/G1 cell arrest of T cells. The major component, leucosceptroid N (32), significantly lowered the levels of IL-6 and TNF-α in peripheral blood serum, and ameliorated the multiorgan damages of LPS-induced sepsis mice at 25 mg/kg dose. These findings suggest that leucosceptrane sesterterpenoids are a new type of potential immunosuppressive agents for sepsis treatment.

Effects of hazards and sensation-seeking on intermediate swimming college students' hazard perceptions.

BACKGROUND: According to the Global Report on Drowning: Preventing a Leading Killer and Preventing Drowning: An Implementation Guide, two documents released by the World Health Organization in 2014 and 2017, respectively, 372,000 people drown each year globally (approximately 42 per hour), half of whom are below 25 years old. Chinese adolescents aged 18-24 years are the main victim group. Intermediate swimming college students are more susceptible to risk-taking behavior and drowning while swimming. In particular, college students with high-sensation-seeking levels have greater confidence in their swimming ability. Consequently, they tend to overestimate their skills and pursue exciting experiences while underestimating or ignoring the risk factors in the situation. The scores of college students in sensation-seeking show a significant positive correlation with highly risky swimming behavior. However, the correlation with the reaction time to hazards is unclear. In this study, using previous theories, the sensation-seeking scale, and the measurement of the reaction time to hazards, we clearly explain why "college students with higher levels of sensation-seeking have a higher risk of drowning." We examined the reaction time to hazards and eye movement data of intermediate swimming college students with different sensation-seeking levels, while controlling the obviousness of hazards in the videos for the experiment. METHODS: We utilized 16 videos of students swimming as experimental stimuli and employed a mixed experimental design of 2 (sensation-seeking: high, low) × 2 (hazard type: obvious hazard, hidden hazard). Sensation-seeking, the between-subjects variable, was categorized into two levels (high and low). The hazard type, the within-subjects variable, was also divided into two categories (obvious and hidden). We analyzed the disparities in reaction time to hazards and eye-movement data between intermediate swimming college students with high (N = 28) or low (N = 28) levels of sensation-seeking. RESULTS: Intermediate swimming college students with high levels of sensation-seeking exhibited significantly longer reaction times to both obvious (F = 6.251, p = .000 < .001) and hidden (F = 49.438, p = .000 < .001) hazards compared to their low-sensation-seeking counterparts. The first fixation duration of intermediate swimming college students on obvious hazards was shorter than that on hidden hazards (F = 13.596, p = .000 < .001), and the average fixation duration of intermediate swimming college students with high levels of sensation-seeking on hidden hazards proved to be significantly shorter (F = 5.498, p = .000 < .001). CONCLUSIONS AND IMPLICATIONS: High-sensation-seeking intermediate swimming college students exhibited longer reaction times to hidden hazards compared to their low-sensation-seeking peers. These findings indicate that a high-sensation-seeking tendency can result in delayed reaction times and a disregard for response measures among intermediate swimming college students.

Multi-Scene Mask Detection Based on Multi-Scale Residual and Complementary Attention Mechanism.

Vast amounts of monitoring data can be obtained through various optical sensors, and mask detection based on deep learning integrates neural science into a variety of applications in everyday life. However, mask detection poses technical challenges such as small targets, complex scenes, and occlusions, which necessitate high accuracy and robustness in multi-scene target detection networks. Considering that multi-scale features can increase the receptive field and attention mechanism can improve the detection effect of small targets, we propose the YOLO-MSM network based on the multi-scale residual (MSR) block, multi-scale residual cascaded channel-spatial attention (MSR-CCSA) block, enhanced residual CCSA (ER-CCSA) block, and enhanced residual PCSA (ER-PCSA) block. Considering the performance and parameters, we use YOLOv5 as the baseline network. Firstly, for the MSR block, we construct hierarchical residual connections in the residual blocks to extract multi-scale features and obtain finer features. Secondly, to realize the joint attention function of channel and space, both the CCSA block and PCSA block are adopted. In addition, we construct a new dataset named Multi-Scene-Mask, which contains various scenes, crowd densities, and mask types. Experiments on the dataset show that YOLO-MSM achieves an average precision of 97.51%, showing better performance than other detection networks. Compared with the baseline network, the mAP value of YOLO-MSM is increased by 3.46%. Moreover, we propose a module generalization improvement strategy (GIS) by training YOLO-MSM on the dataset augmented with white Gaussian addition noise to improve the generalization ability of the network. The test results verify that GIS can greatly improve the generalization of the network and YOLO-MSM has stronger generalization ability than the baseline.

Discovery of Unusual Sesterterpenoids from Colquhounia coccinea var. mollis and Their Metabolic Implications.

Three unusual sesterterpenoids featuring unprecedented rearranged colquhounane (C25) and tetranorcolquhounane (C21) frameworks, colquhounoids E (1) and F (3) and norcolquhounoid F (2), were isolated from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis. Their structures were elucidated by spectroscopic analysis and quantum chemical calculations. A biomimetic inspired regioselective cyclopropane cleavage was achieved under acidic conditions. The immunosuppressive activities of these new sesterterpenoids were also evaluated.

Effect of hydrocolloid dressing on pressure ulcer in patients with non-invasive positive pressure ventilation: A meta-analysis.

This study systematically evaluated the effect of hydrocolloid dressings on facial pressure ulcers in patients receiving non-invasive positive pressure ventilation (NIPPV). The Embase, PubMed, Cochrane Library, CNKI, VIP, Chinese Biomedical Literature Database and Wanfang databases were searched for randomised controlled trials on the use of hydrocolloid dressings in patients receiving NIPPV published from the inception of each database to August 2023. The literature was independently screened, data were extracted by two authors based on the inclusion and exclusion criteria, and the quality of the included literature was assessed. The meta-analysis was performed using Stata 17.0. Thirteen studies including 1248 patients were included, with 639 patients in the intervention group and 609 patients in the control group. Meta-analysis showed that the hydrocolloid dressing significantly reduced the incidence of facial pressure ulcers in patients with NIPPV (odds ratio = 0.16, 95% confidence intervals: 0.11-0.24, p < 0.001). Hydrocolloid dressings are effective in reducing the incidence of facial pressure ulcers in patients receiving NIPPV. However, because of the small number of included studies, this conclusion needs to be confirmed with larger samples and high-quality clinical studies.