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Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen., Competing Interests: Declaration of Competing Interest Yang Yang, Shao-Ping Peng, Yu-Mei Yang, Pan Shu, Pei-Jin Li, Shan Li, Hong-Lin Hu and Ren-Hong Tang are employees of Jiangsu Simcere Pharmaceutical Co., Ltd. Yan Xu is employee of Simcere of America. Other authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. However, at present, research on the role played by CCL5 in the occurrence and development of CRC is still limited, and whether CCL5 promotes the occurrence and development of CRC and its role remain controversial. This paper discusses the cells recruited by CCL5 in patients with CRC and the specific mechanism of this recruitment, as well as recent clinical studies of CCL5 in patients with CRC.Key MessagesCCL5 plays dual roles in colorectal cancer progression.CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action.CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Although the treatment strategies have been improved in recent years, the long-term prognosis of HCC is far from satisfactory mainly due to high postoperative recurrence and metastasis rate. Vascular tumor thrombus, including microvascular invasion (MVI) and portal vein tumor thrombus (PVTT), affects the outcome of hepatectomy and liver transplantation. If vascular invasion could be found preoperatively, especially the risk of MVI, more reasonable surgical selection will be chosen to reduce the risk of postoperative recurrence and metastasis. However, there is a lack of reliable prediction methods, and the formation mechanism of MVI/PVTT is still unclear. At present, there is no study to explore the possibility of tumor thrombus formation from a single circulating tumor cell (CTC) of HCC, nor any related study to describe the possible leading role and molecular mechanism of HCC CTCs as an important component of MVI/PVTT. In this study, we review the current understanding of MVI and possible mechanisms, discuss the function of CTCs in the formation of MVI and interaction with immune cells in the circulation. In conclusion, we discuss implications for potential therapeutic targets and the prospect of clinical treatment of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Ji, Wang, Chen, Ma, Tang, Lin and Zhang.)

Hydrogels are emerging materials for solar steam generation to alleviate water scarcity. Herein, a semiconductor of copper sulfide (CuS) was integrated into cellulose hydrogel to fabricate a solar steam evaporator. Sustainable and low-cost cotton linter (cellulose) was regenerated by NaOH/urea solvent. Epichlorohydrin was added as a cross-linking agent to enhance the mechanical robustness of the composite hydrogel, and CuS crystals were tightly attached to cellulose fibers and uniformly distributed in the hydrogel matrix. Under simulated solar light, a heating zone was established at the top surface of the composite hydrogel, and CuS can efficiently absorb and convert light into heat. The hydrophilic cellulose network affords an adequate water supply and a low water vaporization enthalpy. By tuning the CuS loadings, the optimized evaporation rate and solar-to-vapor efficiency could reach 2.2 kg/m 2 /h and 87 %, respectively, under 1 sun irradiation. The evaporation rate remained above 2.1 kg/m 2 /h after 48 h of irradiation. Moreover, the hydrogels (with a CuS loading of 30 wt%) showed a efficiently photocatalytic degradation of 95 % for methylene blue and 92 % for Rhodamine B. Such functional hydrogel evaporator holds great potential for practical water treatment and solar-driven applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Prcis: There was a significant inverse linear relationship between age at menopause and open angle glaucoma (OAG). Late menarche (≥13 y) and a history of 5 or more deliveries were significantly associated with an increased risk of OAG., Purpose: To determine the association between reproductive factors including age at menarche, age at menopause, reproductive period, parity, and the risk of OAG in women., Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched until February 9, 2022. Studies were included if they assessed the association between reproductive factors and OAG. The adjusted odds ratios (ORs) with relevant 95% CIs were extracted and pooled using fixed-effects models. Besides, we conducted dose-response analyses via the generalized least squares for trend method., Results: Seven articles including 18,618 women were identified in this review. The pooled results indicated that late age at menarche (≥13 y) was significantly associated with an increased risk of OAG (OR=1.76, 95% CI: 1.28, 2.43). Early menopause (<45 y) also significantly elevated the risk of OAG (OR=1.89, 95% CI: 1.23, 2.90) in categorical meta-analyses, consistent with the inverse linear relationship between menopausal age and the risk of OAG in dose-response analyses ( P =0.002). In addition, women who had delivered at least 5 children were at significantly higher risk of OAG compared with those nulliparous (OR=2.35, 95% CI: 1.02, 5.39), and a J-shape relationship between parity and OAG was observed in dose-response analyses ( P <0.001)., Conclusions: Late menarche (≥13 y), early menopause (<45 y), and a history of 5 or more parturitions are possible risk factors for OAG. Longitudinal studies are warranted to further examine the relationships between reproductive factors and the risk of OAG., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Seven previously undescribed cytochalasans, namely, boerechalasins A-G, together with one analogue, were characterized from the solid culture of the fungus Boeremia exigua. Their structures and absolute configurations were elucidated on the basis of extensive spectroscopic analysis as well as electronic circular dichroism calculations. Remarkably, boerechalasin F possessed an unusual sulfoxide moiety that might be derived from methionine, while boerechalasin G had an unusual 5-methylcyclohexane-1,2,3-triol substituent at N-2 position. Boerechalasins A and E exhibited inhibitory activities against nitric oxide production in LPS-induced RAW264.7 macrophages with IC 50 values of 21.9 and 5.7 μM, respectively. Boerechalasin F displayed cytotoxicity against human MCF‒7 cells with an IC 50 value of 22.8 μM., Competing Interests: Declaration of competing interest The corresponding authors, on behalf of all authors of the manuscript, disclose that there is no potential competing or non-financial interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by cessation of menstruation occurring before the age of 40 years. The genetic causes of idiopathic POI remain unclear. Here we recruited a POI patient from a consanguineous family to screen for potential pathogenic variants associated with POI. Genetic variants of the pedigree were screened using whole-exome sequencing analysis and validated through direct Sanger sequencing. A homozygous variant in TUFM (c.524G>C: p.Gly175Ala) was identified in this family. TUFM (Tu translation elongation factor, mitochondrial) is a nuclear-encoded mitochondrial protein translation elongation factor that plays a critical role in maintaining normal mitochondrial function. The variant position was highly conserved among species and predicted to be disease causing. Our in vitro functional studies demonstrated that this variant causes decreased TUFM protein expression, leading to mitochondrial dysfunction and impaired autophagy activation. Moreover, we found that mice with targeted Tufm variant recapitulated the phenotypes of human POI. Thus, this is the first report of a homozygous pathogenic TUFM variant in POI. Our findings highlighted the essential role of mitochondrial genes in folliculogenesis and ovarian function maintenance., (© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Purpose: Ultrashort wave diathermy (USWD) is commonly used in diseases associated with osteoarticular and soft tissue injuries. However, while accelerating wound healing and preventing joint stiffness, there have been few reports on whether it leads to excessive hypertrophic scarring. The aim was to investigate the effects of different doses of USWD on hypertrophic scars., Materials and Methods: A rabbit model of hypertrophic scars was used to determine which dose of USWD reduced scar hyperplasia. The scar thickness was calculated using Sirius red staining. All protein expression levels were determined by western blotting, including fibrosis, collagen deposition, and neoangiogenesis related proteins. Subsequently, flow cytometry and ELISAs were used to determine the proportions of macrophage and inflammatory levels., Results: The wounds with USWD in histopathology showed the dermis was more markedly thickened in the 120 mA group, whereas the wounds with the 60 mA were less raised, comparing with the 0 mA; all detected protein levels were increased significantly, the 120 mA group comparing with the others, including heat shock, fibrosis, and neoangiogenesis, whereas the collagen deposition relative protein levels were decreased, the 60 mA group comparing with Sham group; Finally, in the proportion of macrophages and inflammatory levels the 120 mA group were the highest, and the group Sham was lower than group 60 mA., Conclusions: In hypertrophic scars, the 60 mA USWD could relieve scar formation and inflammatory reactions; however, higher doses could result in opposite consequences.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised concerns worldwide due to its enhanced transmissibility and immune escapability. The first dominant Omicron BA.1 subvariant harbors more than 30 mutations in the spike protein from the prototype virus, of which 15 mutations are located at the receptor binding domain (RBD). These mutations in the RBD region attracted significant attention, which potentially enhance the binding of the receptor human angiotensin-converting enzyme 2 (hACE2) and decrease the potency of neutralizing antibodies/nanobodies. This study applied the molecular dynamics simulations combined with the molecular mechanics-generalized Born surface area (MMGBSA) method, to investigate the molecular mechanism behind the impact of the mutations acquired by Omicron on the binding affinity between RBD and hACE2. Our results indicate that five key mutations, i.e., N440K, T478K, E484A, Q493R, and G496S, contributed significantly to the enhancement of the binding affinity by increasing the electrostatic interactions of the RBD-hACE2 complex. Moreover, fourteen neutralizing antibodies/nanobodies complexed with RBD were used to explore the effects of the mutations in Omicron RBD on their binding affinities. The calculation results indicate that the key mutations E484A and Y505H reduce the binding affinities to RBD for most of the studied neutralizing antibodies/nanobodies, mainly attributed to the elimination of the original favorable gas-phase electrostatic and hydrophobic interactions between them, respectively. Our results provide valuable information for developing effective vaccines and antibody/nanobody drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Human norovirus (HuNoV) is highly infectious and can result in severe illnesses in the elderly and children. So far, there is no effective antiviral drug to treat HuNoV infection, and thus, the development of HuNoV vaccines is urgent. However, NoV evolves rapidly, and currently, at least 10 genogroups with numerous genotypes have been found. The genetic diversity of NoV and the lack of cross-protection between different genotypes pose challenges to the development of broadly protective vaccines. In this study, guided by structural alignment between GI.1 and GII.4 HuNoV VP1 proteins, several chimeric-type virus-like particles (VLPs) were designed through surface-exposed loop grafting. Mouse immunization studies show that two of the designed chimeric VLPs induced cross-immunity against both GI.1 and GII.4 HuNoVs. To our knowledge, this is the first designed chimeric VLPs that can induce cross-immune activities across different genogroups of HuNoV, which provides valuable strategies for the development of cross-reactive HuNoV vaccines., Competing Interests: The authors declare no conflict of interest.

Background: Sessile serrated lesions (SSLs) are often missed on colonoscopy, and studies have shown this to be an essential cause of interstitial colorectal cancer. The SSLs with dysplasia (SSL-D + ), in particular, have a faster rate of carcinogenesis than conventional tubular adenomas. Therefore, there is a clinical need for some endoscopic features with independent diagnostic value for SSL-D + s to assist endoscopists in making immediate diagnoses, thus improving the quality of endoscopic examination and treatment., Aim: To compare the characteristics of SSLs, including those with and without dysplasia (SSL-D + and SSL-D - ), based on white light and image-enhanced endoscopy, to achieve an immediate differential diagnosis for endoscopists., Methods: From January 2017 to February 2023, cases of colorectal SSLs confirmed by colonoscopy and histopathology at the Gastrointestinal Endoscopy Center of Beijing Tsinghua Changgung Hospital were collected. The general, endoscopic, and histopathological data were reviewed and analyzed to determine the diagnostic utility. Univariate analysis was used to find potential diagnostic factors, and then multivariate regression analysis was performed to derive endoscopic features with independent diagnostic values for the SSL-D + ., Results: A total of 228 patients with 253 lesions were collected as a result. There were 225 cases of colorectal SSL-D - s and 28 cases of SSL-D + s. Compared to the colorectal SSL-D - , the SSL-D + was more common in the right colon ( P = 0.027) with complex patterns of depression, nodule, and elevation based on cloud-like surfaces ( P = 0.003), reddish ( P < 0.001), microvascular varicose ( P < 0.001), and mixed type (Pit II, II-O, IIIL, IV) of crypt opening based on Pit II-O ( P < 0.001). Multifactorial logistic regression analysis indicated that lesions had a reddish color [odds ratio (OR) = 18.705, 95% confidence interval (CI): 3.684-94.974], microvascular varicose (OR = 6.768, 95%CI: 1.717-26.677), and mixed pattern of crypt opening (OR = 20.704, 95%CI: 2.955-145.086) as the independent predictors for SSL-D + s., Conclusion: The endoscopic feature that has independent diagnostic value for SSL-D + is a reddish color, microvascular varicose, and mixed pattern of crypt openings., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups ( P =0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.

Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer( P <0.001),and its expression promoted malignant progression of the tumor(all P <0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients( P =0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer( P <0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P <0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P <0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group( P <0.001, P <0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group( P <0.001, P =0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.

Background: Aflatoxin B1 (AFB1), one of the most prevalent contaminants in human and animal food, impairs the immune system, but information on the mechanisms of AFB1-mediated macrophage toxicity is still lacking., Methods and Results: In this study, for the first time, we employed whole transcriptome sequencing technology to explore the molecular mechanism by which AFB1 affects the growth of porcine alveolar macrophages (PAM). We found that AFB1 exposure reduced the proliferative capacity of PAM and prevented cell cycle progression. Based on whole transcriptome analysis, RT-qPCR, ICC and RNAi, we verified the role and regulatory mechanism of the competing endogenous RNA (ceRNA) network in the process of AFB1 exposure affecting the growth of PAM., Conclusions: We found that AFB1 induced MSTRG.43,583, MSTRG.67,490, MSTRG.84,995, and MSTRG.89,935 to competitively bind miR-219a, miR-30b-3p, and miR-30c-1-3p, eliminating the inhibition of its target genes CACNA1S, RYR3, and PRKCG. This activated the calcium signaling pathway to regulate the growth of PAM. These results provide valuable information on the mechanism of AFB1 exposure induced impairment of macrophage function in humans and animals., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Recent studies have suggested that neuropilin-1 (NRP1) may serve as a potential receptor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the biophysical characteristics of interactions between NRP1 and SARS-CoV-2 remain unclear. In this study, we examined the interactions between NRP1 and various SARS-CoV-2 spike (S) fragments, including the receptor-binding domain (RBD) and the S protein trimer in a soluble form or expressed on pseudovirions, using atomic force microscopy and structural modeling. Our measurements shows that NRP1 interacts with the RBD and trimer at a higher binding frequency (BF) compared to ACE2. This NRP1-RBD interaction has also been predicted and simulated via AlphaFold2 and molecular dynamics simulations, and the results indicate that their binding patterns are very similar to RBD-ACE2 interactions. Additionally, under similar loading rates, the most probable unbinding forces between NRP1 and S trimer (both soluble form and on pseudovirions) are larger than the forces between NRP1 and RBD and between trimer and ACE2. Further analysis indicates that NRP1 has a stronger binding affinity to the SARS-CoV-2 S trimer with a dissociation rate of 0.87 s -1 , four times lower than the dissociation rate of 3.65 s -1 between NRP1 and RBD. Moreover, additional experiments show that RBD-neutralizing antibodies can significantly reduce the BF for both ACE2 and NRP1. Together, the study suggests that NRP1 can be an alternative receptor for SARS-CoV-2 attachment to human cells, and the neutralizing antibodies targeting SARS-CoV-2 RBD can reduce the binding between SARS-CoV-2 and NRP1., (© 2023 The Protein Society.)

Objective: To investigate the risk factors of surgical site infection (SSI) after colorectal surgery, and to establish and validate a risk prediction model nomogram. Methods: An observational study was conducted to retrospectively collect data of 6527 patients aged ≥16 years who underwent colorectal surgery in 56 domestic hospitals from March 1, 2021 to February 28, 2022 from the national Surgical Site Infection Surveillance network. The incidence of SSI after surgery was 2.3% (149/6527). According to the ratio of 7:3, 6527 patients were randomly divided into the modeling cohort (4568 cases) and the validation cohort (1959 cases), and there was no statistically significant difference between the two datasets ( P >0.05). Univariate analysis was performed using t test /Mann-Whitney U test /χ 2 test. Multivariate analysis was performed using binary logistic regression to establish a preliminary model and select variables using Lasso analysis to establish an optimized model nomogram. The discrimination and calibration of the model were evaluated by ROC curve, calibration curve, and Hosmer-Lemeshow test. AUC value>0.7 is considered a good discrimination of the model. The Bootstrap method (repeated self-sampling 1000 times) was used to verify the constructed model internally and externally to evaluate the accuracy of the constructed model. Results: Multivariate analysis showed that history of chronic liver disease (OR=3.626, 95%CI: 1.297-10.137, P <0.001) and kidney disease (OR=1.567,95%CI:1.042-2.357, P =0.038), surgical antibiotic prophylaxis (OR=1.564, 95%CI:1.038-2.357, P =0.035), and emergency surgery (OR=1.432,95%CI: 1.089-1.885, P =0.021), open surgery (OR=1.418, 95%CI:1.045-1.924, P =0.042), preoperative stoma (OR=3.310, 95%CI:1.542-7.105, P <0.001), postoperative stoma (OR=2.323,95%CI: 1.537-8.134, P <0.001), surgical incision type above grade II (OR=1.619,95%CI:1.097-2.375, P =0.014), and each unit increase in total bilirubin (OR=1.003,95%CI:-0.994-1.012, P =0.238), alanine aminotransferase (OR=1.006, 95%CI:1.001-1.011, P =0.032), blood urea nitrogen (OR=1.003,95%CI:0.995-1.011, P =0.310), blood glucose (OR=1.024, 95%CI:1.005-1.043, P =0.027), C-reactive protein (OR=1.007, 95%CI:1.003-1.011, P <0.001), length of incision (OR=1.042, 95%CI:1.002-1.087, P =0.031), surgical duration (OR=1.003,95%CI:1.001-1.005, P =0.017), and surgical blood loss (OR=1.001,95%CI: 1.000-1.002, P =0.045) were risk factors for SSI after colorectal surgery. Each unit increase in albumin level (OR=0.969,95%CI:0.941-0.998, P =0.036) was an independent protective factor for SSI after colorectal surgery. The area under the curve of the optimized model obtained by internal and external validation were 0.768 (95%CI: 0.723-0.813) and 0.753 (95%CI: 0.680-0.832), respectively. The predicted value of the calibration curve was basically consistent with the actual value. Conclusions: The risk prediction model for SSI after colorectal surgery constructed in this study has good discrimination and calibration. The nomogram created in this model can provide an evaluation basis for the observed rate and expected event rate of SSI after clinical colorectal surgery.

Boron-dipyrromethene (BODIPY) derivatives are prospective organic-based triplet photosensitizers. Since the triplet generation yield of the parent BODIPY is low, heavy atoms are widely used to improve the triplet yield. However, the dimerization of BODIPYs can also significantly improve their ability to produce triplets. Through a comparative study of the triplet formation dynamics of two heavy-atom-free orthogonal covalent BODIPY heterodimers that differ in their dihedral angles, we have demonstrated that the mechanism of spin-orbit charge-transfer intersystem crossing (SOCT-ISC) promotes the triplet generation of BODIPY heterodimers in solution. Different from the general understanding of SOCT-ISC, the heterodimer with a smaller dihedral angle and low structural rigidity showed better triplet generation due to (a) the stronger inter-chromophoric interaction in the heterodimer, which promoted the formation of a solvent-stabilized charge-transfer (CT) state, (b) the more favorable energy level alignment with sizeable spin-orbit coupling strength, and (c) the balance between the stabilized singlet CT state and limited direct charge recombination to the ground state in a weakly polar solvent. The complete spectral characterization of the triplet formation dynamics clarified the SOCT-ISC mechanism and important factors affecting the triplet generation in BODIPY heterodimers.

Advances in single-atom (-site) catalysts (SACs) provide a new solution of atomic economy and accuracy for designing efficient electrocatalysts. In addition to a precise local coordination environment, controllable spatial active structure and tolerance under harsh operating conditions remain great challenges in the development of SACs. Here, we show a series of molecule-spaced SACs (msSACs) using different acid anhydrides to regulate the spatial density of discrete metal phthalocyanines with single Co sites, which significantly improve the effective active-site numbers and mass transfer, enabling one of the msSACs connected by pyromellitic dianhydride to exhibit an outstanding mass activity of (1.63 ± 0.01) × 10 5 A·g -1 and TOF bulk of 27.66 ± 1.59 s -1 at 1.58 V ( vs RHE) and long-term durability at an ultrahigh current density of 2.0 A·cm -2 under industrial conditions for oxygen evolution reaction. This study demonstrates that the accessible spatial density of single atom sites can be another important parameter to enhance the overall performance of catalysts.

Objective: To observe the skin surface microcirculation of acupoints of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea using laser speckle contrast imaging (LSCI), and provide acupoint selection basis of acupuncture-moxibustion for primary dysmenorrhea., Methods: Ninety-nine healthy female college students with regular menstrual cycles (normal group) and 94 female college students with primary dysmenorrhea (dysmenorrhea group) were recruited. Before menstrual period, on the first day of menstruation, and on the third day after menstruation, LSCI was used to observe the surface microcirculation at the abdominal acupoints of conception vessel, i. e. Yinjiao (CV 7), Qihai (CV 6), Shimen (CV 5), Guanyuan (CV 4), Zhongji (CV 3) and Qugou (CV 2), acupoints of thoroughfare vessel, i. e. Huangshu (KI 16), Zhongzhu (KI 15), Siman (KI 14), Qixue (KI 13), Dahe (KI 12), Henggu (KI 11) and acupoints of lumbosacral region of governor vessel, i. e. Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3), Yaoshu (GV 2) as well as two non-acupoints., Results: Before menstrual period, there was no significant difference in the surface blood perfusion of the acupoints between the dysmenorrhea group and the normal group ( P >0.05). On the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) and right Huangshu (KI 16) in the dysmenorrhea group was higher than that in the normal group ( P <0.05, P <0.01). On the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) in the dysmenorrhea group was lower than that in the normal group ( P <0.05)., Conclusion: In patients with primary dysmenorrhea, on the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) of governor vessel, and the right Huangshu (KI 16) of thoroughfare vessel is increased, while on the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) of thoroughfare vessel is decreased. These findings might provide a basis for acupoint selection in the acupuncture-moxibustion treatment of primary dysmenorrhea.

Alcohol use is a major risk factor for the burden of mortality and morbidity. Alcoholic cirrhosis (AC) and alcoholic liver cancer (ALC) are most important and severe liver disease outcomes caused by alcohol use. The objectives of the current study were to investigate the global prevalence and burden of disease in disability-adjusted life years (DALYs) for AC and ALC, based on data from the Global Burden of Disease (GBD). Incidence, prevalence, death, and DALYs for GBDs in different locations, years, sex, and age groups were estimated using DisMod-MR 2.1 and a generic Cause of Death Ensemble Modeling approach. The correlations between the age-standardized incidence rate or age-standardized death rate and gender, sociodemographic index (SDI), and alcohol usage were conducted by Generalized Linear Models. Globally, the changes of age-standardized rates of indicators were not much significant over the 30-year period. However, the changes varied widely across regions. Central Asia and East Europe contributed the highest age-standardized incidence, prevalence, death, and DALYs and increased sharply by past 30 years. Generalized Linear Models (GLMs) showed male gender as a risk factor of AC, with the relative risk of incidence of 1.521 and relative risk of death of 1.503. Globally, there were improvements in overall health with regard to GBDs over the 30 years. However, the prevention of AC and ALC should be promoted in middle and middle-high SDI regions, especially Central Asia and East Europe, whereas more medical resources should be provided to improve treatment levels in low SDI region., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of the study is to explore the mechanism of tribbles pseudokinase 3 (TRIB3)-regulated Akt pathway in the development of preeclampsia (PE)., Study Design: TRIB3 expression in the placenta of PE patient was determined by quantitative reverse transcriptase polymerase chain reaction and western blotting. Then HTR-8/SVneo or JEG-3 cells were transfected and divided into Mock, Control siRNA, TRIB3 siRNA-1, and TRIB3 siRNA-2 groups. Cell proliferation, invasion, and migration were determined by MTT assay, Transwell assay, and wound healing test, while the expression of TRIB3 and Akt pathway was measured by western blotting. PE rats were treated with TRIB3 siRNA, and blood pressure, 24-hour urinary protein, as well as serum levels of sFlt-1 and vascular endothelial growth factor (VEGF) were measured., Results: The placenta of PE patients presented with increased TRIB3 expression. In comparison with Mock group, the proliferation, invasion, and migration of HTR-8/SVneo and JEG-3 cells in TRIB3 siRNA-1 group and TRIB3 siRNA-2 group increased, with decreased TRIB3 expression but enhanced expression of p-Akt/Akt, MMP-2, and MMP-9. Rats in PE group showed increases in mean arterial pressure, SBP, 24-hour urinary protein, and serum sFlt-1 levels, but decreases in serum VEGF levels, fetal weight, and placental efficiency. Moreover, TRIB3 expression was upregulated, while p-Akt/Akt was downregulated in the placenta of rats in PE group. However, indicators above were significantly improved in rats treated with TRIB3 siRNA., Conclusion: TRIB3 was upregulated in the PE placenta, while silencing TRIB3 activated the Akt signaling pathway to promote the invasion and migration of trophoblast both in vitro and in vivo and ameliorated the development of PE symptoms in the PE rat model., Key Points: · The TRIB3 expression was increased in the placenta of PE patient. · Silencing TRIB3 activates Akt signal pathway.. · Silencing TRIB3 improves the pathological process of preeclampsia rat.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: To assess the relationship between sleep duration and the risk of major eye disorders including myopia, glaucoma, cataract, age-related macular degeneration (AMD), and diabetic retinopathy (DR)., Methods: Databases including PubMed, Embase, Web of Science, and Cochrane library were searched for eligible publications before July 2021. Studies assessing the relationship between sleep duration and any one of the major eye disorders were identified. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were estimated using random-effects models., Results: We identified 21 relevant articles including 777348 participants, and 17 were cross-sectional, 3 were longitudinal, and 1 was case-control. Pooled results indicated that long sleep duration was significantly associated with the risk of DR (OR = 1.84, 95% CI 1.24, 2.73), and short sleep duration was significantly associated with the risk of cataract (OR = 1.20, 95% CI 1.05, 1.36). Besides, a significant relationship was observed between the risk of DR and long sleep duration per day (i.e., nighttime sleep plus daytime napping, OR = 1.74, 95% CI 1.23, 2.44) rather than per night (OR = 2.17, 95% CI 0.95, 4.99). The extreme of long sleep duration (i.e., >10 h per night) increased the risk of myopia (OR = 1.02, 95% CI 1.01, 1.04)., Conclusions: Inappropriate sleep duration might increase the risk of major eye disorders. The findings could contribute to the growing knowledge on the possible relationship between circadian rhythms and eye disorders., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

The role of ASMase/ceramide signaling pathway in the development of silicosis needs to be verified by in vivo experiments. We investigated the role of the ASMase/ceramide signaling pathway in the progression of silicosis and the effect of desipramine (DMI) (1 mg/mL) on the development of silicosis, by establishing a silica (1 mL, 50 mg/mL) dust-contaminated rat silicosis model and administering the ASMase inhibitor, DMI, to the dust-contaminated rats. The results showed that the levels of interleukin (IL)-1β and IL-6 were increased in the lung tissues of the rats in the dust-contaminated group at the initial stage after dusting; the inflammatory cell aggregation in the lung tissue was increased. With time progression, the hydroxyproline content in the lung tissue increased, and alpha-smooth muscle actin (α-SMA), collagen I, and vimentin substantially increased, suggesting that silicosis was formed in the lung tissue of the rats 28 days after SiO 2 dust treatment. Moreover, the levels of ASMase, ceramide, and sphingosine-1-phosphate (S1P) were increased in the lung tissue of rats. The expression of β-catenin, fibronectin, and caspase-3 protein was increased, and E-cadherin protein expression was decreased in the lung tissue of the rats in the late stage of dust contamination. The ASMase and ceramide in the lung tissues of the rats in the DMI intervention group were reduced, as were the lung tissue inflammation levels, collagen expression, and lung fibrosis. These results suggest that SiO 2 dust may activate the ASMase/ceramide signaling pathway in rat lung tissue, promoting pulmonary fibrosis. DMI inhibited this activation, attenuated apoptosis, blocked epithelial-mesenchymal transition, and halted silica dust-induced silicofibrosis., (© 2023 John Wiley & Sons Ltd.)

Background: Results of previous studies about the prognostic roles of histone H4 lysine 16 acetylation (H4K16ac) and histone H4 lysine 20 trimethylation (H4K20me3) in breast cancer were inconsistent. Cellular experiments revealed the interplays between H4K16ac and H4K20me3, but no population study explored the interaction between them on the prognosis., Methods: H4K16ac and H4K20me3 levels in tumors were evaluated by immunohistochemistry for 958 breast cancer patients. Hazard ratios for overall survival (OS) and progression-free survival (PFS) were estimated using Cox regression models. Interaction was assessed on multiplicative scale. Concordance index (C-index) was calculated to verify the predictive performance., Results: The prognostic roles of the low level of H4K16ac or H4K20me3 were significant only in patients with the low level of another marker and their interactions were significant. Moreover, compared with joint high levels of both them, only the combined low levels of both them was associated with a poor prognosis but not the low level of single one. The C-index of the clinicopathological model combined the joint expression of H4K16ac and H4K20me3 [0.739 for OS; 0.672 for PFS] was significantly larger than that of the single clinicopathological model [0.699 for OS, P < 0.001; 0.642 for PFS, P = 0.003] or the model combined with the single H4K16ac [0.712 for OS, P < 0.001; 0.646 for PFS, P < 0.001] or H4K20me3 [0.724 for OS, P = 0.031; 0.662 for PFS, P = 0.006]., Conclusions: There was an interaction between H4K16ac and H4K20me3 on the prognosis of breast cancer and the combination of them was a superior prognostic marker compared to the single one., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Object: There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms., Methods: GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions., Results: Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software's MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p., Conclusion: Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhang, Fang, Li, Shu, Gong, Luo and Tian.)

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal tumor worldwide and its late discovery and lack of effective specific therapeutic agents necessitate further research into its pathogenesis and treatment. Organoids, a novel model that closely resembles native tumor tissue and can be cultured in vitro, have garnered significant interest in recent years, with numerous reports on the development of organoid models for liver cancer. In this study, we have successfully optimized the procedure and established a culture protocol that enables the formation of larger-sized HCC organoids with stable passaging and culture conditions. We have comprehensively outlined each step of the procedure, covering the entire process of HCC tissue dissociation, organoid plating, culture, passaging, cryopreservation, and resuscitation, and provided detailed precautions in this paper. These organoids exhibit genetic similarity to the original HCC tissues and can be utilized for diverse applications, including the identification of potential therapeutic targets for tumors and subsequent drug development.

Background: The prognostic role of either forkhead box A1 (FOXA1) or anterior gradient 2 (AGR2) in breast cancer has been found separately. Considering that there were interplays between them depending on ER status, we aimed to assess the statistical interaction between AGR2 and FOXA1 on breast cancer prognosis and examine the prognostic role of the combination of them by ER status., Methods: AGR2 and FOXA1 expression in tumor tissues were evaluated with tissue microarrays by immunohistochemistry in 915 breast cancer patients with follow up data. The expression levels of these two markers were treated as binary variables, and many different cutoff values were tried for each marker. Survival and Cox proportional hazard analyses were used to evaluate the relationship between AGR2, FOXA1 and prognosis, and the statistical interaction between them on the prognosis was assessed on multiplicative scale., Results: Statistical interaction between AGR2 and FOXA1 on the PFS was significant with all the cutoff points in ER-positive breast cancer patients but not ER-negative ones. Among ER-positive patients, the poor prognostic role of the high level of FOXA1 was significant only in patients with the low level of AGR2, and vice versa. When AGR2 and FOXA1 were considered together, patients with low levels of both markers had significantly longer PFS compared with all other groups., Conclusions: There was a statistical interaction between AGR2 and FOXA1 on the prognosis of ER-positive breast cancer. The combination of AGR2 and FOXA1 was a more useful marker for the prognosis of ER-positive breast cancer patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Biochar has high carbon stability and is a good carbon sequestration material. Sludge biochar is rich in inorganic minerals, which would provide enrichment in the preparation process of pyrolysis, affecting its carbon sequestration capacity in practice. In this study, municipal sludge biochar (SZB), pharmaceutical sludge biochar (YCB), and chicken manure biochar (JFB) were prepared under the pyrolysis process at 500, 600, and 700℃, respectively, and their aging process in soil for 70-100 years was simulated. The physicochemical properties and the carbon loss calculation of the biochars were determined using elemental analysis, FTIR, XRF, ICP, and XRD. The results demonstrated that the type and mass fraction of endogenous minerals in the biochars determined their carbon loss during pyrolysis. Ca and Mg were the main carbon-protecting minerals, whereas Fe may have reduced the carbon stability of the sludge biochars and therefore increased the carbon loss. For the aging process, the stability of the endogenous carbon in the biochars played a major role in its carbon loss, whereas the endogenous minerals played a supporting role. These findings elucidated the effect of the stability of endogenous carbon and the composition of mineral components on the carbon loss of biochars, which may provide references for soil carbon sequestration using sludge and chicken manure biochar.

Soil fungi are essential to soil microorganisms that play an important role in the ecosystem's soil carbon cycle and mineral nutrient transformation. Understanding the structural characteristics and diversity of soil fungal communities helps understand the health of forest ecosystems. The transition from tropical rainforest to artificial forest greatly impacts the composition and diversity of fungal communities. Hainan Limushan tropical rainforest National Park has a large area of artificial forests. Ecologists have conducted in-depth studies on the succession of animals and plants to regenerate tropical rainforests. There are few reports on the diversity of soil fungi and its influencing factors in the succession of tropical rainforests in Limu Mountain. In this study, 44 soil samples from five different stands were collected in the tropical rainforest of Limushan, Hainan. High-throughput sequencing of rDNA in its region was used to analyze fungal communities and study their α and β diversity. Analysis of variance and multiple regression models was used to analyze soil variables and fungal functional groups to determine the effects of interaction between fungi and environmental factors. A total of 273,996 reads and 1290 operational taxonomic units (OTUs) were obtained, belonging to 418 species, 325 genera, 159 families, eight phyla, 30 classes, and 73 orders. The results showed that the composition of soil fungal communities in the five stands was similar, with ascomycetes accounting for 70.5% and basidiomycetes accounting for 14.7%. α and β diversity analysis showed that soil fungi in Limushan tropical rainforest had high abundance and diversity. Multiple regression analysis between soil variables and functional groups showed that organic matter, TN, TP, TK, and AK were excellent predictors for soil fungi. TP was the strongest predictor in all functional groups except soil saprotroph. Organic matter and total nitrogen were the strongest predictors of soil rot. The transformation from tropical rainforest to artificial forest in Limushan did not change the soil fungal community structure, but the richness and diversity of soil fungi changed. The forest transformation did not lead to decreased soil fungal abundance and diversity. Different vegetation types and soil properties affect the diversity of soil fungal communities. We found that Caribbean pine plantations can improve soil fungal diversity, while long-term Eucalyptus spp. plantations may reduce soil fungal diversity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: N6-methyladenosine (m 6 A) is the most common post-transcriptional modification of RNA in eukaryotes, which has been demonstrated to play important roles in various biological processes. However, its roles in fulminant hepatitis remain largely unknown. In the current study, YTHDF1 expression was found to be significantly downregulated in the livers among patients, as well as murine models with fulminant hepatitis versus normal controls. Thus, we hypothesized that YTHDF1 protects against fulminant hepatitis and investigated the underlying molecular mechanisms. Methods: Fulminant hepatitis was induced by D-GalN/LPS in conventional YTHDF1 knockout (YTHDF1 -/- ) mice, hepatocyte-specific YTHDF1 overexpression (AAV8- YTHDF1) mice, and corresponding control mice. Primary hepatocytes were cultured and subjected to LPS insult in vitro . Hepatic histology, cell death, oxidative stress and mitochondrial function were examined to assess liver damage. The molecular mechanisms of YTHDF1 function were explored using multi-omics analysis. Results: Ablation of YTHDF1 exacerbated hepatic apoptosis and reactive oxygen species (ROS) production and increased the number of aberrant mitochondria, while YTHDF1 overexpression resulted in the opposite effects. Multiomics analysis identified MFG-E8 as the direct target of YTHDF1. YTHDF1 augmented the translation of MFG-E8 in an m 6 A-dependent manner without effect on its mRNA expression, thereby restoring mitochondrial function. Additionally, administration of MFG-E8 almost completely reversed the YTHDF1 deficiency-mediated exacerbation of liver injury. Conclusions: The current study suggested that the m 6 A reader YTHDF1 alleviates cell death, enhances antioxidant capacity and restores mitochondrial function in fulminant hepatitis by promoting MFG-E8 protein translation in an m 6 A-dependent manner., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

SO 2 , a gas signaling molecule, can be produced endogenously in mitochondria. Its hydrolysate, HSO 3 - , plays a key role in food preservation, cardiovascular relaxation, and other fields, suggesting that it is important to achieve its detection. Here, based on the Michael addition mechanism, four hemicyanine dye fluorescent probes ( ETN , ETB , STB , and EIB ) were designed and synthesized for responding to HSO 3 - . We evaluated the reaction ability of different probes with HSO 3 - and tried to explain the reasons for the significantly different response effects between probes and HSO 3 - according to the structure-activity relationship. The influence of different substituents of probes on the properties of mitochondria-targeting was also discussed. Finally, we screened out ETN as the optimal HSO 3 - probe due to its high sensitivity, rapid reactivity, and good mitochondria-targeting, and it could sensitively respond to HSO 3 - in living cells. The LODs of ETN for HSO 3 - were calculated by both absorption and fluorescence methods, respectively, which were 2.727 and 0.823 μM. Our work provided valuable references for designing strategies and potential tools for response to SO 2 derivatives in biosystems.

Aflatoxins B1 (AFB1), a type I carcinogen widely present in the environment, not only poses a danger to animal husbandry, but also poses a potential threat to human reproductive health, but its mechanism is still unclear. To address this question, multi-omics were performed on porcine Sertoli cells and mice testis. The data suggest that AFB1 induced testicular damage manifested as decreased expression of GJA1, ZO1 and OCCLUDIN in mice (p < 0.01) and inhibition of porcine Sertoli cell proliferation. Transcriptomic analysis suggested changes in noncoding RNA expression profiles that affect the cell cycle-related Ras/PI3K/Akt signaling pathway after AFB1 exposure both in mice and pigs. Specifically, AFB1 caused abnormal cell cycle of testis with the characterization of decreased expressions of CCNA1, CCNB1 and CDK1 (p < 0.01). Flow cytometry revealed that the G2/M phase was significantly increased after AFB1 exposure. Meanwhile, AFB1 downregulated the expressions of Ras, PI3K and AKT both in porcine Sertoli cell (p < 0.01) and mice testis (p < 0.01). Metabolome analysis verified the alterations in the PI3K/Akt signaling pathway (p < 0.05). Moreover, the joint analysis of metabolome and microbiome found that the changes of metabolites were correlated with the expression of flora. In conclusion, we have demonstrated that AFB1 impairs testicular development via the cell cycle-related Ras/PI3K/Akt signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Infectious diseases including COVID-19 and mental disorders are two of the most common health conditions associated with stigma. However, the comparative stigma of these two conditions has received less attention in research. This study aimed to compare the prevalence of stigmatizing views toward people with COVID-19 and mental disorders and the factors associated with these views, among a large sample of adolescent and young adult students in China., Methods: A total of 9,749 adolescents and young adults aged 15-24 years completed a survey on stigmatizing attitudes toward COVID-19 and mental disorders, as well as mental health-related factors, including general mental health status and symptoms of depression, anxiety, insomnia, and post-traumatic stress disorder (PTSD). Multivariable linear regression analyses were conducted to identify factors associated with stigmatizing views., Findings: The prevalence of COVID-19 and mental disorders-related stigma was 17.2% and 40.7%, respectively. COVID-19-related stigma scores were significantly higher among male students (β = 0.025, p < 0.05), those without quarantine experience (β = 0.035, p < 0.001), those with lower educational level ( p < 0.001), those with lower family income ( p < 0.01), and those with higher PTSD symptoms (β = 0.045, p < 0.05). Mental disorder-related stigma scores were significantly higher among individuals with average and lower-than-average levels of family income ( p < 0.01), depression symptoms (β = 0.056, p < 0.001), anxiety symptoms (β = 0.051, p < 0.001), and mental health problems (β = 0.027, p < 0.05)., Conclusion: The stigma of mental disorders is higher in the youth population than the stigma of COVID-19. Factors associated with stigmatizing attitudes toward people with COVID-19 and mental disorders varied across the youth. Stigma-reduction interventions among the youth should be targeted specifically to COVID-19 or mental disorders conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhang, Meng, Huang, Zhang, Gong, Chan, Chen, Gao, Lewis-Fernández, Fan, Liu, Huang, Deng, Liu and Ran.)

Background: AURKA, Aurora kinase A encoding gene, is an important signaling hub gene for mitosis. In recent years, AURKA has been implicated in the occurrence and development of several cancers. However, its relationship with the tumor microenvironment in skin cutaneous melanoma (SKCM) and the molecular mechanisms underlying its effects are still unclear., Method: We adopted a variety of bioinformatics methods to comprehensively analyze the potential carcinogenesis of AURKA in SKCM, and constructed a prognostic nomogram model. We also dentified an inhibitor targeting AURKA and verified its therapeutic effects against SKCM using the molecular docking technology., Results: We found that abnormally high expression of AURKA was responsible for driving the occurrence and development of SKCM, and affected various pathological factors in SKCM. In addition, AURKA was established as an independent marker of poor SKCM prognosis. We also characterized the potential mechanisms by which AURKA manifests its effects in SKCM and found that AURKA inhibits the infiltration of CD8+ T cells and promotes hypoxia by activating the TGF-β signaling pathway. At the same time, the high AURKA expression group had higher tumor stemness index and promoted cell proliferation and metastasis. Finally, the small-molecule compound ZNC97018978 targeting AURKA screened by molecular docking technology can inhibit the proliferation, invasion and metastasis of SKCM. The possible mechanism is that ZNC97018978 induces apoptosis by arresting the cell cycle, thereby inhibiting cell proliferation., Conclusion: AURKA is the core hub gene driving the occurrence and development of SKCM, and its expression is regulated by epigenetic modifications. AURKA can regulate the infiltration level of various immune cells in the tumor microenvironment, reshape the immunosuppressive tumor microenvironment, and apoptosis, and hypoxia. Thus, it is a prognostic biomarker and potential therapeutic target in SKCM. ZNC97018978 is an effective and safe inhibitor of AURKA in vitro; its safety and effectiveness in vivo as a potential treatment for cutaneous melanoma should be further determined., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Our study aimed to explore the intellectual function of patients with Duchenne muscular dystrophy (DMD) in China and examine the correlation of full-scale intelligence quotient (FSIQ) with age, mutation locations, mutation class, and dystrophin isoforms. We assessed 64 boys with DMD using The Wechsler Intelligence Scales for Children-Fourth Edition and compared intellectual function at enrollment and follow-up in the 15 patients who completed the follow-up. Our findings confirm that boys with DMD may exhibit cognitive impairment, with the Working Memory Index being the most impaired. There was no significant correlation between FSIQ and age; however, a positive correlation was noted between age and the Verbal Comprehension Index. FSIQ was not associated with mutation class, the number of affected mutated exons, or mutation locations. However, there was a significant difference in FSIQ between the groups with intact and deficient Dp140. Fifteen participants adhered to glucocorticoid therapy throughout the two-year follow-up period, and eleven of them showed an improvement in FSIQ compared to their initial scores, with improvement ranging from 2 to 20. In conclusion, patients with the cumulative loss of isoforms in the brain are at a higher risk of cognitive deficits and may require early cognitive interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We present an optical method for the manipulation of microparticles using two tilted-focused beams. First, the action on the microparticles is studied with a single tilted-focused beam. The beam is used to drive the directional motion of a dielectric particle. When the optical scattering force is larger than the optical gradient force, the particle is pushed to the tilted side of the optical axis by the optical force. Second, two tilted-focused beams with the same power and complementary tilt angles are used to assemble an optical trap. The trap can be used to realize the optical trapping of the dielectric particles and opto-thermal trapping of the light absorbing particles. The trapping mechanism is the balance of the forces exerted on the particles, including the optical scattering force, optical gradient force, gravity, and thermal gradient force. The trap center is away from the focal spots, which effectively prevents the laser beam from being focused on the trapped object., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

The recent advances in single-cell RNA sequencing (scRNA-seq) techniques have stimulated efforts to identify and characterize the cellular composition of complex tissues. With the advent of various sequencing techniques, automated cell-type annotation using a well-annotated scRNA-seq reference becomes popular. But it relies on the diversity of cell types in the reference, which may not capture all the cell types present in the query data of interest. There are generally unseen cell types in the query data of interest because most data atlases are obtained for different purposes and techniques. Identifying previously unseen cell types is essential for improving annotation accuracy and uncovering novel biological discoveries. To address this challenge, we propose mtANN (multiple-reference-based scRNA-seq data annotation), a new method to automatically annotate query data while accurately identifying unseen cell types with the aid of multiple references. Key innovations of mtANN include the integration of deep learning and ensemble learning to improve prediction accuracy, and the introduction of a new metric that considers three complementary aspects to distinguish between unseen cell types and shared cell types. Additionally, we provide a data-driven method to adaptively select a threshold for identifying previously unseen cell types. We demonstrate the advantages of mtANN over state-of-the-art methods for unseen cell-type identification and cell-type annotation on two benchmark dataset collections, as well as its predictive power on a collection of COVID-19 datasets. The source code and tutorial are available at https://github.com/Zhangxf-ccnu/mtANN., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xiong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A cell line expressing the CD2v protein of ASFV was generated. The efficient expression of CD2v protein was determined by immunofluorescence and Western blotting. The CD2v protein was Ni-affinity purified from the supernatant of cell cultures. The CD2v-expressing cells showed properties of hemadsorption, and the secreted CD2v protein exhibited hemagglutinating activity. The antigenicity and immunoprotection ability of CD2v were evaluated by immunizing pigs alone, combined with a cell-line-expressed p30 protein or triple combined with p30 and K205R protein. Immunized pigs were challenged with the highly virulent ASFV strain HLJ/18. Virus challenge results showed that CD2v immunization alone could provide partial protection at the early infection stage. Protein p30 did not show synergistic protection effects in immunization combined with CD2v. Interestingly, immunization with the triple combination of CD2V, p30 and K205R reversed the protection effect. The viremia onset time was delayed, and one pig out of three recovered after the challenge. The pig recovered from ASFV clinical symptoms, the rectal temperature returned to normal levels and the viremia was cleared. The mechanism of this protection effect warrants further investigation.

Background: Premature ovarian insufficiency (POI) patients present with a chronic inflammatory state. Cell-free mitochondria DNA (cf-mtDNA) has been explored as a reliable biomarker for estimating the inflammation-related disorders, however, the cf-mtDNA levels in POI patients have never been measured. Therefore, in the presenting study, we aimed to evaluate the levels of cf-mtDNA in plasma and follicular fluid (FF) of POI patients and to determine a potential role of cf-mtDNA in predicting the disease progress and pregnancy outcomes., Methods: We collected plasma and FF samples from POI patients, biochemical POI (bPOI) patients and control women. Quantitative real-time PCR was used to measure the ratio of mitochondrial genome to nuclear genome of cf-DNAs extracted from the plasma and FF samples., Results: The plasma cf-mtDNA levels, including COX3, CYB, ND1 and mtDNA79, were significantly higher in overt POI patients than those in bPOI patients or control women. The plasma cf-mtDNA levels were weakly correlated with ovarian reserve, and could not be improved by regular hormone replacement therapy. The levels of cf-mtDNA in FF, rather than those in plasma, exhibited the potential to predict the pregnancy outcomes, although they were comparable among overt POI, bPOI and control groups., Conclusions: The increased plasma cf-mtDNA levels in overt POI patients indicated its role in the progress of POI and the FF cf-mtDNA content may hold the value in predicting pregnancy outcomes of POI patients., (© 2023. The Author(s).)

Aim: To evaluate the effect of 0.05% atropine on the control of myopia for 2y (phase I) and on spherical equivalent refraction (SER) progression for 1y (phase II) after its withdrawal in Chinese myopic children., Methods: Totally 142 children with myopia were randomly assigned to the 0.05% atropine group or to the placebo group. In phase I, children received 1 treatment for each eye daily. In phase II, the patients received no treatment. Axial length (AL), SER, intraocular pressure (IOP) and atropine-related side effects were assessed at 6 months' intervals., Results: During phase I, the mean change of SER was -0.46±0.30 D in the atropine group, compared to -1.72±1.12 D in the placebo group ( P <0.001). The mean change of AL in the atropine group (0.26±0.30 mm) was significantly shorter than that in the placebo group (0.76±0.62 mm, P =0.002). In addition, in phase II (12mo after the withdrawal of atropine), there was no significant difference in AL change from the atropine group, when compared with that from the placebo group (0.31±0.25 mm vs 0.28±0.26 mm, P >0.05). Furthermore, the change in SER from the atropine group was 0.50±0.41 D, which was significantly lower than 0.72±0.60 D from placebo group, ( P <0.05). Finally, there were no statistically significant differences in IOP between the treatment and control groups at any stages (all P >0.05)., Conclusion: The use of 0.05% atropine for two consecutive years may effectively control elongation of AL and thus progression of myopia, without significant SER progression 1y after atropine withdrawal. Therefore, treatment with 0.05% atropine daily for 2y is effective and safe., (International Journal of Ophthalmology Press.)

Objective: To investigate the prevalence of anisometropia and associated parameters among school-aged children in Nantong, China., Methods: This school-based, cross-sectional study examined students from primary schools, junior high schools, and senior high schools in an urban area of Nantong, China. Univariate and multivariate logistic regression analyses were used to investigate the specific correlations between anisometropia and related parameters. Non-cycloplegic autorefraction was assessed for each student. Anisometropia was defined as the spherical equivalent refraction (SE) difference ≥ 1.0 D between eyes., Results: A total of 9,501 participants were validated for analyses, of which 53.2% ( n  = 5,054) were male, and 46.8% ( n  = 4,447) were female. The mean of age was 13.32 ± 3.49 years, ranging from 7-19 years. The overall prevalence of anisometropia was 25.6%. Factors such as myopia, scoliosis screening positive, hyperopia, female sex, older age, and higher weight had a significantly higher risk of anisometropia ( p  < 0.05)., Conclusion: There was a high prevalence of anisometropia in school-age children. Some physical examination parameters are closely related to children's anisometropia, especially myopia and scoliosis. Preventing myopia and controlling its progression may be the most important ways to reduce the prevalence of anisometropia. Correcting scoliosis may be an important factor in controlling the prevalence of anisometropia, and maintaining good reading and writing posture may be helpful in controlling the prevalence of anisometropia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Zhang, Chen, Wang, Cai, Xiong, Song and Sun.)

Cellulose-based ionic conductive hydrogels (ICHs) have found extensive applications in flexible electronics and multifunctional sensors. However, simultaneous realization of sufficient conductivity, superior mechanical property and extreme environment tolerance for ICHs remains to be a huge challenge. In this work, a facile one-pot approach was developed to fabricate ICHs by directly dissolving cotton linter cellulose and polyvinyl alcohol (PVA) in a concentrated ZnCl 2 solution. By regulating the content of PVA in ICHs, the optimal hydrogel (Gel-5) exhibits a tensile strength of 0.30 MPa, a compressive strength of 2.05 MPa and a conductivity of 8.16 S m -1 . Moreover, the resulting dual-network ICHs present high transparency, good thermal reversibility and desirable ionic conductivity. Due to the high concentration of inorganic salts in the porous dual-network structure, the ICH presents good anti-drying and anti-freezing (as low as -90 °C) properties. Such hydrogel can be assembled into multi-functional sensors for human motion and temperature monitoring, and they demonstrate durable sensitivity, cycling stability in a wide operating temperature. This work will shed light on the design of cellulose-based hydrogels with good ionic conductivity and mechanical performance under extreme conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In order to improve the position high-precision synchronization performance of multi-motor synchronous control, a multi-motor position synchronization control method based on non-singular fast terminal sliding mode control (NFTSMC) combined with an improved deviation coupling control structure (Improved Deviation Coupling Control(IDCC), NFTSMC+IDCC). Firstly, this paper designs a sliding mode controller using a non-singular fast terminal sliding mode surface with a Permanent Magnet Synchronous Motor (PMSM) as the control object. Secondly, the deviation coupling is improved to enhance the coupling between multiple motors and achieve position synchronization. Finally, the simulation results show that the total error of multi-motor position synchronization under NFTSMC control is 0.553r in the simulation of multi-motor synchronization control under the same working conditions, which is 2.873r and 1.772r less than that of SMC and FTSMC in terms of speed error, and the anti-disturbance performance is 83.68% and 76.22% higher than that of both of them, respectively. In the subsequent simulation of the improved multi-motor position synchronization structure, the total error of the multi-motor position is in the range of 0.56r-0.58r at three speeds, which is much smaller than the synchronization error under the Ring Coupling Control (RCC) structure and Deviation Coupling Control (DCC) structure, showing a better The synchronization error is much smaller than that of the RCC structure and DCC structure, which shows better position synchronization performance. Therefore, the multi-motor position synchronization control method proposed in this paper has a good position synchronization effect and achieves the control effect of small displacement error and fast convergence of the multi-motor position synchronization control system after being disturbed, the control performance is significantly improved., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To assess the impacts of area-level socioeconomic and environmental measures on reduced visual acuity (VA)., Methods: This ecological study used the nationally representative cross-sectional data from the Chinese National Survey on Students' Constitution and Health in 2014 (CNSSCH 2014), which included 261,833 participants aged 7 to 22 years randomly selected from 30 mainland provinces in China. Area-level socioeconomic measures assessed included gross domestic product (GDP), population density, density of hospital beds, and nighttime light data measured as the mean digital number (DN) of each region; environmental factors assessed included latitude, annual sunlight duration, and park green space density. The main outcome measure was the prevalence of reduced VA in each province of Mainland China., Results: GDP (coefficient: 0.221; P < 0.001), mean DN (coefficient: 0.461; P < 0.001), latitude (coefficient: 0.093; P < 0.001), and annual sunlight duration (coefficient: 0.112; P < 0.001) were positively associated with the prevalence of reduced VA, while population density (coefficient: -0.256; P < 0.001), park green space per 10,000 people (coefficient: -0.145; P < 0.001), and number of hospital beds per 10,000 people (coefficient: -0.146; P < 0.001) were negatively associated with reduced VA prevalence. Factor analysis indicated a marginally nonsignificant positive correlation between socioeconomic factors and the prevalence of reduced VA (coefficient: 0.034; P = 0.07)., Conclusions: Increased GDP and mean DN, which reflect economic development, were associated with a higher prevalence of reduced VA, while larger park green space and number of hospital beds per 10,000 people seemed to play a protective role, which could be targeted to design preventive strategies for myopia.

The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes. Its special anatomical and physiological structure renders it susceptible to nerve injury. The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone. This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions. Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. In monoculture, glial cell line-derived neurotrophic factor promoted the migration of Schwann cells, but it did not have effects on the migration of astrocytes. In the co-culture system, glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells. Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes. However, in the co-culture system, brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree. These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone. This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions., Competing Interests: None

Background: The basic endoscopic instruments are not suitable for removing calcified or hard discs in patients with thoracic disc herniations (TDH). We describe a percutaneous endoscopic technique for the treatment of calcified TDH using an endoscopic drill system with a T rigid bendable burr., Methods: Eleven patients (8 males, mean age 42.1 years) with single-segmental calcified TDH were treated with percutaneous endoscopic surgeries., Results: Our technique using this endoscopic drill system with a T rigid bendable burr is safe and effective for the treatment of calcified TDH., Conclusions: Percutaneous endoscopic decompression using the T rigid bendable burr is a safe and reproducible surgical procedure for the treatment of calcified TDH.