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Bullying is one of the most common forms of school violence. Although the negative impact of bullying victimization on students' mental health outcomes has been well documented, the underlying mechanism of the association lacks investigation, especially in the rural Chinese boarding school context. This study examined (1) the associations between bullying victimization and mental health (i.e., subjective well-being and depressive symptoms), and (2) the mediating roles of cognitive reappraisal and expressive suppression in Chinese boys and girls from a rural boarding school in Gansu province. This cross-sectional study involved 655 Chinese rural adolescents in a boarding school in Gansu province (M[subscript age] = 15.68 years, SD = 0.96; 408 girls). Structural equation modelling (SEM) was used to evaluate the mediation model, and the bootstrap approach was used to test the indirect effect. The total effects from bullying victimization to subjective well-being (for boys: [beta] = - 0.32, p < 0.001; for girls: [beta] = - 0.35, p < 0.001) and depressive symptoms (for boys: [beta] = 0.29, p < 0.001; for girls: [beta] = 0.32, p < 0.001) were significant in boys and girls. The indirect effect of bullying victimization through cognitive reappraisal on subjective well-being ([beta] = -0.11, 95% CI - 0.17 to - 0.06) and depressive symptoms ([beta] = 0.09, 95% CI 0.05 to 0.15) was significant in girls, whereas the indirect effect was not significant in boys. The indirect effect through expressive suppression was not significant in both boys and girls. This study extends the literature by demonstrating the underlying mechanism linking bullying victimization to poor mental health. Gender differences were identified regarding the indirect effects. These findings have cultural implications for bullying victimization intervention on Chinese rural adolescents' mental health.

Abstract This retrospective cohort study aimed to evaluate the association between pre-existing heart failure and both mortality and the recurrence of sepsis. A total of 16,092 sepsis patients without a history of heart failure and 841 sepsis patients with pre-existing heart failure were identified from the Medical Information Mart for Intensive Care version IV (MIMIC-IV ) database. All patients were adults admitted to intensive care units, and no specific interventions were applied. After matching, Kaplan–Meier survival analysis showed significantly poorer long-term survival rates in patients with heart failure, both in the original (p

Abstract Understanding the genetic factors related to meat drip loss is of great importance for animal breeding and production. In this study, we employed a combination of genome‐wide association study (GWAS) mapping and RNA sequencing (RNA‐seq) data to effectively identify potentially functional single nucleotide polymorphisms (SNPs) as well as candidate genes associated with drip loss (DL) in Beijing Black pigs. Initially, we conducted a single‐ and multi‐trait GWAS on drip loss traits in 441 Beijing Black pigs at 24 (DL24) and 48 (DL48) hours postmortem using the Illumina pig 50K SNP chip. Five SNPs with annotations for four genes (FGGY, LHFPL6, OSBPL1A, and NMNAT3) were consistently identified in single or multiple trait GWAS results, indicating their potential pleiotropic effects on drip loss. Next, a comprehensive comparative transcriptomic analysis was performed on samples of Beijing Black pigs exhibiting extremely high and low drip loss, resulting in the identification of 21 differentially expressed genes (DGEs) as potential candidates. Additionally, protein–protein interaction (PPI) network analysis revealed reciprocal regulatory relationships between FOXO1, OSBPL1A, DOCK1 (identified from GWAS) and the candidate DGEs obtained from RNA‐seq data. Therefore, we propose that these genes may impact drip loss traits through gene interactions. In conclusion, our integrative analysis screened candidate genes that may affect the drip loss traits in Beijing Black pigs, which provides crucial insights into the molecular mechanisms of drip loss and serves as a theoretical reference for improving meat quality in Beijing Black pigs.

Abstract Background Postoperative time to extubation plays a role in prognosis after heart valve surgery; however, its exact impact has not been clarified. This study compared the postoperative outcomes of minimally invasive surgery and conventional sternotomy, focusing on early extubation and factors influencing prolonged mechanical ventilation. Methods Data from 744 patients who underwent heart valve surgery at the Zhejiang Provincial People’s Hospital between August 2019 and June 2022 were retrospectively analyzed. The outcomes in patients who underwent conventional median sternotomy (MS) and minimally invasive (MI) video-assisted thoracoscopic surgery were compared using inverse probability of treatment weighting (IPTW) and Kaplan–Meier curves. Clinical data, including surgical data, postoperative cardiac function, postoperative complications, and intensive care monitoring data, were analyzed. Results After propensity score matching and IPTW, 196 cases of conventional MS were compared with 196 cases of MI video-assisted thoracoscopic surgery. Compared to patients in the conventional MS group, those in the MI video-assisted thoracoscopic surgery group in the matched cohort had a higher early postoperative extubation rate (P

ObjectiveTo construct an evaluation index system for the development level of county-level chronic disease management centers, providing a basis for evaluating and comparing the construction of these centers. MethodsFocusing on the key points of county-level chronic disease management center construction and combining relevant literature, a candidate index database was constructed. Twenty-nine experts in the field of chronic disease management were selected to conduct two rounds of Delphi consultation to determine the evaluation index system for the development level of county-level chronic disease management centers, and the analytic hierarchy process was used to determine the index weights. ResultsThe active participation rates of experts in the two rounds of Delphi consultation were 90.91% and 96.67%, respectively, with expert authority coefficients of 0.85 and 0.84, and Kendall′s W of 0.15 and 0.20 (both P < 0.001). After two rounds of consultation, a final evaluation index system for the development level of county-level chronic disease management centers was constructed, consisting of 5 dimensions and 45 indicators: organizational management and basic conditions, chronic disease management informatization, county-township collaborative management of chronic diseases, capacity building and quality control of chronic disease management, and quality and effectiveness of chronic disease management. The weights of the 5 dimensions were 0.212 2, 0.180 1, 0.219 4, 0.179 4, and 0.208 9, respectively. ConclusionThe evaluation index system for the development level of county-level chronic disease management centers constructed in this study is reasonable, practical, representative, and instructive, providing a reference basis for evaluating the development level of these centers and key directions for subsequent construction.

Abstract Background Environmental temperature is critical in regulating biological functions in fish. S. prenanti is a kind of cold-water fish, but of which we have little knowledge about the metabolic adaptation and physiological responses to long-term cold acclimation. Results In this study, we determined the physiological responses of S. prenanti serum after 30 days of exposure to 6℃. Compared with the control group, the levels of TC, TG, and LDL-C in the serum were significantly (P

Abstract Low serum cholesterol levels are associated with increased tumor morbidity and mortality. However, the relationship between serum lipid profile and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is still unclear. The aim of our study was to clarify the importance of the serum lipid profile in predicting the severity and prognosis of patients with POEMS syndrome. Forty-three patients with newly diagnosed POEMS syndrome admitted to the Department of Hematology of Jiangsu Provincial People's Hospital between August 2013 and February 2023 were selected. They had explicit serum lipid profiles. There were 27 males and 16 females with a median age of 54 years (range, 28–77 years). Survival curves were plotted using the Kaplan–Meier method, and comparisons between the two groups were performed using the log-rank test. The Cox proportional-hazards model examined risk factors associated with the prognosis of POEMS syndrome. Receiver-operator characteristic (ROC) curves assessed the predictive accuracy. 23 (53.5%) patients had low total cholesterol (TC) levels. Low levels of TC were concerned with unfavorable progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.004), and at the same time, the low circulating TC concentration was an independent risk factor for PFS (p = 0.020) and OS (p = 0.011). Low TC values could improve the risk stratification, especially in high-risk patients. In conclusion, low serum TC levels may predict inferior prognosis in patients with POEMS syndrome; in future clinical application, low TC may be a reliable indicator of prognosis.

To investigate Gyrodactylus infection of fish in the river system of Xinjiang (China), Gyrodactylus individuals were isolated from specimens of Diptychus maculatus. Morphological characterization and phylogenetic analysis based on ITS1-5.8S-ITS2 rDNA locus revealed that the gyrodactylids belong to new species. Gyrodactylus diptychi n. sp. differs significantly in the morphology of the haptoral structures from 12 known species of Gyrodactylus found in fishes of the subfamily Schizothoracinae. In particular, G. diptychi n. sp. has a relatively short dorsal bar with thick and large ends, flat and straight hamuli roots, and small ventral bar processes. Furthermore, G. diptychi n. sp. is the only representative of Gyrodactylus found on D. maculatus. Using the BLASTn search of ITS1-5.8S-ITS2 rDNA sequences in GenBank and the Bayesian Information and Maximum Likelihood methods, we constructed phylogenetic trees for G. diptychi n. sp. As a result, our studies clearly identified that G. diptychi n. sp. was the first Gyrodactylus monogenean isolated from D. maculatus and a new species belonged to the subgenus Limnonephrotus.

Hypertrophy of ligamentum flavum (LF) is a significant contributing factor to lumbar spinal canal stenosis (LSCS). lncRNA plays a vital role in organ fibrosis, but its role in LF fibrosis remains unclear. Our previous findings have demonstrated that Hedgehog-Gli1 signaling is a critical driver leading to LF hypertrophy. Through the RIP experiment, our group found lnc-RMRP was physically associated with Gli1 and exhibited enrichment in Gli1-activated LF cells. Histological studies revealed elevated expression of RMRP in hypertrophic LF. In vitro experiments further confirmed that RMRP promoted Gli1 SUMO modification and nucleus transfer. Mechanistically, RMRP induced GSDMD-mediated pyroptosis, proinflammatory activation, and collagen expression through the Hedgehog pathway. Notably, the mechanical stress-induced hypertrophy of LF in rabbit exhibited analogous pathological changes of LF fibrosis occurred in human and showed enhanced levels of collagen and α-SMA. Knockdown of RMRP resulted in the decreased expression of fibrosis and pyroptosis-related proteins, ultimately ameliorating fibrosis. The above data concluded that RMRP exerts a crucial role in regulating GSDMD-mediated pyroptosis of LF cells via Gli1 SUMOylation, thus indicating that targeting RMRP could serve as a potential and effective therapeutic strategy for LF hypertrophy and fibrosis.

Abstract The aim of the study was to evaluate the prognostic impact of minimal residual disease (MRD) in the real-world setting and the interaction between MRD and molecular risk, clinical response and autologous stem-cell transplant (ASCT). A retrospective analysis of 275 newly diagnosed multiple myeloma (NDMM) patients who achieved very good partial remission (VGPR) or better before maintenance were involved. We examined MRD status by multiparameter flow cytometry (MFC). At a median follow-up of 37 months (4–88 months), In patients who achieved ≥ VGPR, those with MRD negativity had significantly longer PFS (51 vs. 26 months; P

Objective: The objective of this study was to explore the influence of traditional laparoscopic surgery and transumbilical single-port laparoscopic surgery on ovarian function in patients with benign ovarian tumours. Materials and Methods: Forty-four patients with benign ovarian tumours who were treated in our hospital from January 2020 to June 2021 were selected and randomly divided into two groups, with 22 cases in each group according to random number table. The conventional group was treated with conventional laparoscopic surgery, while the modified group was treated with transumbilical single-port laparoscopic surgery. The measurement method was t-test, and the enumeration method was two tests. The clinical operation-related indicators, ovarian function (follicle-stimulating hormone, E2 and luteinising hormone), complication incidence, Visual Analogue Scale (VAS) and landscaping satisfaction scores of the two groups were compared. Results: There were no significant differences in complications and operation duration between the two groups (P > 0.05). After treatment, the ovarian function indexes and beautification satisfaction scores of the modified group were significantly superior to those of the conventional group (P < 0.05). Besides, the intraoperative bleeding volume, post-operative exhaust time, hospital stay and three-dimensional VAS scores on day 1 and day 3 after surgery of the modified group were lower than those of the conventional group (P < 0.05). Conclusion: Transumbilical single-port laparoscopic surgery for benign ovarian tumours has a significant clinical effect, which can effectively reduce bleeding during the operation, improve ovarian function, relieve surgical pain, promote rapid post-operative recovery and improve patients' satisfaction with landscaping. It is worthy of clinical application.

Yili River system hosts a diverse fauna of fishes and parasites. Gymnodiptychus dybowskii is a rare and endangered aboriginal cold-water fish inhabit in the Yili river system. Our research identified a new species Gyrodactylus gymnodiptychi n. sp. isolated from G. dybowskii in the Kunes River (Yili River, China). Morphological comparison revealed identifiable differences between the new species and other parasites, including Gyrodactylus aksuensis, and Gyrodactylus tokobaevi, which are two known parasites living in G. dybowskii inhabit in the Aksu River west of Frunze (Kyrgyzstan), as well as Gyrodactylus montanus living in Shizothorax intermedius inhabited in the Tadzhikistan or Uzbekistan. Especially, the dorsal bar of G. gymnodiptychi n. sp. was raised at both ends with a hollow, and its hamulus roots were curved inward. The BLASTN search of GenBank did not detect any other ITS1-5.8S-ITS2 rDNA sequences same as G. gymnodiptychi's. Using the Bayesian Information and Maximum Likelihood methods to analyze the ITS1-5.8S-ITS2 rDNA gene sequences, we constructed phylogenetic trees for G. gymnodiptychi n. sp. Accordingly, our morphological and molecular research indicated that G. gymnodiptychi n. sp. was not only a new species of parasites but also the first Gyrodactylus member identified in the Yili River in China.

Semen is a complex fluid that contains spermatozoa and also functions as a dynamic bacterial microecosystem, comprising probiotics, pathogenic bacteria, and natural antimicrobial substances. Probiotic bacteria, such as Lactobacillus and Bifidobacterium, along with pathogenic bacteria like Pseudomonas aeruginosa and Escherichia coli, play significant roles in semen preservation and reproductive health. Studies have explored the impact of pathogenic bacteria on sperm quality, providing insights into the bacterial populations in mammalian semen and their influence on sperm function. These reviews highlight the delicate balance between beneficial and harmful bacteria, alongside the role of natural antimicrobial substances that help maintain this equilibrium. Moreover, we discuss the presence and roles of antimicrobial substances in semen, such as lysozyme, secretory leukocyte peptidase inhibitors, lactoferrin, and antimicrobial peptides, as well as emerging antibacterial substances like amyloid proteins. Understanding the interactions among probiotics, pathogens, and antimicrobial agents is crucial for elucidating semen preservation and fertility mechanisms. Additionally, the potential for adding probiotic bacteria with recombinant antibacterial properties presents a promising avenue for the development of new semen extenders. This review offers updated insights to understand the equilibrium of the bacterial microecosystem in semen and points toward innovative approaches for improving semen preservation.

Abstract Cerebrospinal fluid (CSF) leak can be diagnosed in clinical laboratories by detecting a diagnostic marker β2-transferrin (β2-Tf) in secretion samples. β2-Tf and the typical transferrin (Tf) proteoform in serum, β1-transferrin (β1-Tf), are Tf glycoforms. An innovative affinity capture technique for sample preparation, called microprobe-capture in-emitter elution (MPIE), was incorporated with high-resolution mass spectrometry (HR-MS) to study the Tf glycoforms and the primary structures of β1-Tf and β2-Tf. To implement MPIE, an analyte is first captured on the surface of a microprobe, and subsequently eluted from the microprobe inside an electrospray emitter. The capture process is monitored in real-time via next-generation biolayer interferometry (BLI). When electrospray is established from the emitter to a mass spectrometer, the analyte is immediately ionized via electrospray ionization (ESI) for HR-MS analysis. Serum, CSF, and secretion samples were analyzed using MPIE-ESI-MS. Based on the MPIE-ESI-MS results, the primary structures of β1-Tf and β2-Tf were elucidated. As Tf glycoforms, β1-Tf and β2-Tf share the amino acid sequence but contain varying N-glycans: (1) β1-Tf, the major serum-type Tf, has two G2S2 N-glycans on Asn413 and Asn611; and (2) β2-Tf, the major brain-type Tf, has an M5 N-glycan on Asn413 and a G0FB N-glycan on Asn611. The resolving power of the innovative MPIE-ESI-MS method was demonstrated in the study of β2-Tf as well as β1-Tf. Knowing the N-glycan structures on β2-Tf allows for the design of more novel test methods for β2-Tf in the future.

Abstract Asian dust delivers highly reactive iron (FeHR) to the Pacific Ocean, affecting marine biogeochemical cycles and Earth's climate. Tracing the source of dust deposited in the Pacific is vital for assessing global nutrient cycles but poses challenges. This work applies the (234U/238U) activity ratio to determine the pre‐deposition time and provenance of dust in North Pacific Ocean sediments (Ocean Drilling Program site 1209B). Results indicate a consistent dust pre‐deposition time (134 ± 10 ka) over the past 300,000 years, except during Marine Isotope Stage 7 when volcanic ash input shortened it to 31 ± 19 ka. Comparing the dust pre‐deposition times to those of the potential source deserts, we identify the dust transported to the North Pacific Ocean was primarily from the Taklamakan Desert, which contains higher FeHR content than other deserts. This finding enhances our understanding of soluble Fe supplied to the oceans, especially in dust circulation models.

Angiogenesis is essential for tumour growth and metastasis. Antiangiogenic factor-targeting drugs have been approved as first line agents in a variety of oncology treatments. Clinical drugs frequently target the VEGF signalling pathway during sprouting angiogenesis. Accumulating evidence suggests that tumours can evade antiangiogenic therapy through other angiogenesis mechanisms in addition to the vascular sprouting mechanism involving endothelial cells. These mechanisms include (1) sprouting angiogenesis, (2) vasculogenic mimicry, (3) vessel intussusception, (4) vascular co-option, (5) cancer stem cell-derived angiogenesis, and (6) bone marrow-derived angiogenesis. Other non-sprouting angiogenic mechanisms are not entirely dependent on the VEGF signalling pathway. In clinical practice, the conversion of vascular mechanisms is closely related to the enhancement of tumour drug resistance, which often leads to clinical treatment failure. This article summarizes recent studies on six processes of tumour angiogenesis and provides suggestions for developing more effective techniques to improve the efficacy of antiangiogenic treatment.

Abstract Chronic pain is a major cause of suffering that often accompanies diseases and therapies, affecting approximately 20% of individuals at some point in their lives. However, current treatment modalities, such as anesthetic and antipyretic analgesics, have limitations in terms of efficacy and side effects. Nanomedical technology offers a promising avenue to overcome these challenges and introduce new therapeutic mechanisms. This article reviews the recent research on nanomedicine analgesics, integrating analyses of neuroplasticity changes in neurons and pathways related to the transition from acute to chronic pain. Furthermore, it explores potential future strategies using nanomaterials, aiming to provide a roadmap for new analgesic development and improved clinical pain management. By leveraging nanotechnology, these approaches hold the potential to revolutionize pain treatment by delivering targeted and effective relief while minimizing side effects.

[This corrects the article DOI: 10.1371/journal.pone.0125429.].

Summary: The canine transmissible venereal tumor (CTVT) is a clonal cell-mediated cancer with a long evolutionary history and extensive karyotype rearrangements in its genome. However, little is known about its genetic similarity to human tumors. Here, using multi-omics data we identified 11 germline gene fusions (GGFs) in CTVT, which showed higher genetic susceptibility than others. Additionally, we illustrate a mechanism of a complex gene fusion of three gene segments (HSD17B4-DMXL1-TNFAIP8) that we refer to “greedy fusion”. Our findings also provided evidence that expressions of GGFs are downregulated during the tumor regressive phase, which is associated with DNA methylation level. This study presents a comprehensive landscape of gene fusions (GFs) in CTVT, which offers a valuable genetic resource for exploring potential genetic mechanisms underlying the development of cancers in both dogs and humans.

AbstractBackground: Extramedullary disease (EMD) is an unusual event in patients with MM. This study aimed to assess the prognostic impact of EMD and develop an EMD-based risk model to estimate the survival of patients with newly diagnosed multiple myeloma (NDMM).Methods: A total of 518 patients were enrolled in this study, of which 121 presented with EMD at the initial diagnosis. Patients were divided into non-EMD, extramedullary-bone-related (EM-B) and extramedullary-extraosseous (EM-E) groups. Clinical characteristics were compared using the chi-squared test or Fisher’s exact test. Survival curves were plotted using the Kaplan-Meier method, and a nomogram was constructed based on the Cox proportional hazards model.Results: Compared to patients without EMDs, patients with EM-E were younger (p = 0.028), and those with EM-B had less renal damage (p

A silicon (Si)/silicon carbide (4H–SiC) heterojunction double-trench metal-oxide-semiconductor field effect transistor (MOSFET) (HDT-MOS) with the gate-controlled tunneling effect is proposed for the first time based on simulations. In this structure, the channel regions are made of Si to take advantage of its high channel mobility and carrier density. The voltage-withstanding region is made of 4H–SiC so that HDT-MOS has a high breakdown voltage (BV) similar to pure 4H–SiC double-trench MOSFETs (DT-MOSs). The gate-controlled tunneling effect indicates that the gate voltage (VG) has a remarkable influence on the tunneling current of the heterojunction. The accumulation layer formed with positive VG can reduce the width of the Si/SiC heterointerface barrier, similar to the heavily doped region in an Ohmic contact. This narrower barrier is easier for electrons to tunnel through, resulting in a lower heterointerface resistance. Thus, with similar BV (approximately 1770 ​V), the specific on-state resistance (RON-SP) of HDT-MOS is reduced by 0.77 ​mΩ‧cm2 compared with that of DT-MOS. The gate-to-drain charge (QGD) and switching loss of HDT-MOS are 52.14​% and 22.59​% lower than those of DT-MOS, respectively, due to the lower gate platform voltage (VGP) and the corresponding smaller variation (ΔVGP). The figure of merit (QGD ​× ​RON-SP) of HDT-MOS decreases by 61.25​%. Moreover, the heterointerface charges can reduce RON-SP of HDT-MOS due to trap-assisted tunneling while the heterointerface traps show the opposite effect. Therefore, the HDT-MOS structure can significantly reduce the working loss of SiC MOSFET, leading to a lower temperature rise when the devices are applied in the system.

AIM:To observe the changes in corneal aberrations and the characteristics of visual quality after transepithelial photorefractive keratectomy(T-PRK)and femtosecond small incision lenticule extraction(SMILE)in the correction of low myopia.METHODS: Prospective cohort study. A total of 32 cases(32 eyes)with low myopia who underwent T-PRK surgery and 45 cases(45 eyes)of SMILE surgery at Weifang Eye Hospital from April 2021 to April 2022 were selected. The uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical equivalent(SE), corneal higher-order aberrations(HOAs)and objective visual quality were compared between the two groups.RESULTS:All patients completed the surgery successfully without complications such as infection. At 3mo postoperatively, the safety index was 1.13±0.16 and 1.16±0.17(P=0.48)and the efficacy index was 1.10±0.20 and 1.15±0.18(P=0.27)in the T-PRK and SMILE groups, respectively. The percentage of UCVA(LogMAR)≤0 in the T-PRK and SMILE groups was 94% and 98%, respectively. The percentage of the residual SE within ±0.5D was 88% and 87% in the two groups, respectively. The HOAs and spherical aberration in both groups were significantly increased(P≤0.01), and the increase was not statistically significant between the two groups(P=0.31, 0.89). There was no significant change in horizontal coma, horizontal trefoil and vertical trefoil in both groups(P>0.05). The vertical coma in SMILE group was significantly increased(P0.05), and the increase was significantly greater in SMILE group than in T-PRK group(P0.05).CONCLUSION:Both T-PRK and SMILE showed good safety, efficacy, and visual quality in correcting low myopia, while SMILE induced more vertical coma than T-PRK.

AIM: To investigate the short-term visual quality outcomes after femtosecond laser small incision lenticule extraction(SMILE)and evolution implantable collamer lens(EVO-ICL)implantation for the correction of moderate myopia.METHODS: Prospective control study. A total of 51 cases(51 eyes)with moderate myopia who underwent SMILE or EVO-ICL implantation surgery at Weifang Eye Hospital from April 2021 to February 2022 were selected. They were divided into SMILE group(30 patients, 30 eyes)and EVO-ICL group(21 patients, 21 eyes)according to the surgical methods. The changes of visual acuity [uncorrected distance visual acuity(UDVA), corrected distance visual acuity(CDVA)], diopter [spherical equivalent(SE)] and related parameters of optical quality analysis system(OQAS Ⅱ)were observed before surgery and at 1wk, 1 and 3mo after surgery, and the quality of vision(QoV)questionnaire was completed.RESULTS: At 3mo after surgery, the safety index(postoperative CDVA/preoperative CDVA)of SMILE gruop and EVO-ICL group were 1.20(1.00, 1.20)and 1.20(1.00, 1.38), respectively, the efficacy index(postoperative UDVA/preoperative CDVA)were 1.00(1.00, 1.20)and 1.00(1.00, 1.20), respectively, and the percentage of SE within ±0.50D was 87% and 100%, respectively. In SMILE group, the objective scattering index(OSI)was increased after surgery, while modulation transfer function cutoff frequency(MTF cutoff), contrast visual acuity(VA)100%, and VA20% at 1wk and 1mo after surgery, and Strehl ratio(SR)and VA9% at each time point after surgery were all decreased compared with those before surgery(all P0.05). The most common visual symptoms after SMILE and EVO-ICL implantation were visual haze and halos, respectively.CONCLUSION: Both SMILE and EVO-ICL implantation have good safety, efficacy and predictability in the short term after the correction of moderate myopia. Both groups had visual symptoms after surgery, but the overall satisfaction of patients was high. Furthermore, EVO-ICL implantation has better objective visual quality performance.

Abstract Radix Astragali is one of the most famous and frequently used health food supplements and herbal medicines. Among more than 227 components of Radix Astragali, Astragaloside IV (AG IV) is famous functional compound and is commonly used as a quality marker for Radix Astragali. However, the relatively low content of AG IV in Radix Astragali (

Introduction: Therapeutic drug monitoring (TDM) of immunosuppressants is essential for optimal care of transplant patients. Immunoassays and liquid chromatography-mass spectrometry (LC-MS) are the most commonly used methods for TDM. However, immunoassays can suffer from interference from heterophile antibodies and structurally similar drugs and metabolites. Additionally, nominal-mass LC-MS assays can be difficult to optimize and are limited in the number of detectable compounds. Objectives: The aim of this study was to implement a mass spectrometry-based test for immunosuppressant TDM using online solid-phase extraction (SPE) and accurate-mass full scan-single ion monitoring (FS-SIM) data acquisition mode. Methods: LC-MS analysis was performed on a TLX-2 multi-channel HPLC with a Q-Exactive Plus mass spectrometer. TurboFlow online SPE was used for sample clean up. The accurate-mass MS was set to positive electrospray ionization mode with FS-SIM for quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A. MS2 fragmentation pattern was used for compound confirmation. Results: The method was validated in terms of precision, analytical bias, limit of quantitation, linearity, carryover, sample stability, and interference. Quantitation of tacrolimus, sirolimus, everolimus, and cyclosporine A correlated well with results from an independent reference laboratory (r = 0.926–0.984). Conclusions: Accurate-mass FS-SIM can be successfully utilized for immunosuppressant TDM with good correlation with results generated by standard methods. TurboFlow online SPE allows for a simple “protein crash and shoot” sample preparation protocol. Compared to traditional MRM, analyte quantitation by FS-SIM facilitates a streamlined assay optimization process.

Abstract Background The proteasome in eukaryotic cells can degrade a variety of proteins and plays an important role in regulating the cell cycle, cell survival and apoptosis. The proteasome receives much attention as a potential chemotherapeutic target for treatment of a variety of infectious parasitic diseases, but few studies of proteasomes have been done on parasitic nematodes. Methods A proteasomal β5 subunit encoding gene (named Hc-pbs-5) and its inferred product (Hc-PBS-5) in Haemonchus contortus were identified and characterized in this study. Then, the transcriptional profiles and anatomical expression were studied using an integrated molecular approach. Finally, a specific proteasome inhibitor bortezomib (BTZ), together with RNA interference (RNAi), was employed to assess the function of Hc-PBS-5. Results Bioinformatic analysis revealed that the coding sequence of Hc-pbs-5 was 855 bp long and encoded 284 amino acids (aa). The predicted protein (Hc-PBS-5) had core conservative sequences (65–250 aa) belonging to N-terminal nucleophile (Ntn) family of hydrolases. Real-time PCR results revealed that Hc-pbs-5 was continuously transcribed in eight developmental stages with higher levels at the infective third-stage larvae (L3s) and adult males of H. contortus. Immunohistochemical results revealed that Hc-PBS-5 was expressed in intestine, outer cuticle, muscle cells under the outer cuticle, cervical glands and seminal vesicles of male adults and also in intestine, outer cuticle, cervical glands, uterine wall, eggs and ovaries of female adults of H. contortus. BTZ could reduce proportions of egg hatching, and the fourth-stage larvae (L4s) developed from the exsheathed L3s (xL3s) of H. contortus. In addition, silencing Hc-pbs-5 by soaking the specific double-stranded RNA (dsRNA) could decrease the transcription of Hc-pbs-5 and result in fewer xL3s developing to L4s in vitro. Conclusions These results indicate that proteasomal β5 subunit plays an important role in the growth, development and life span of H. contortus. Graphical Abstract

Regarding applicative, facile, green chemical research, a bio-inspired approach is being reported for the synthesis of CuO nanoparticles by pectin (PEC) as a natural reducing and stabilizing agentin alkaline medium without using any toxic reducing agent. The biosynthesized CuO NPs@Pectin were characterized by advanced physicochemical techniques like ultraviolet–visible (UV–Vis), Fourier Transformed Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX) and X-ray Diffraction (XRD) study. It has been established that pectin-stabilized copper nanoparticles have a spherical shape with a mean diameter from approximately 10 nm. To survey the cytotoxicity and anti-human cervical cancer effects of CuO NPs@Pectin, MTT assay was used on C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3 and LM-MEL-41 cell lines. The resulting IC50 values of the CuO NPs@Pectin against C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3 and LM-MEL-41 cell lines were 231, 214, 243, 376, 315 and 169 µg/mL, respectively. Antioxidant properties of CuO NPs@Pectin were surveyed through the DPPH test in presence of butylated hydroxytoluene as the positive control. The CuO NPs@Pectin inhibited half of the DPPH molecules in the concentration of 98 µg/mL. The cell viability of the treated cell lines was found to reduce dose-dependently over the CuO NPs@Pectin nanocomposite. After approving the above results in the clinical trial studies, the CuO NPs@Pectin can be used as a chemotherapeutic drug for the treatment of several types of cervical cancers.

Construction of heterojunction has been considered as an efficient strategy to enhance the gas-sensing performances of metal oxide semiconductors. On this basis, hierarchical In2O3/In2S3 microsphere heterostructures were synthesized by partial oxidation of In2S3 precursors which were obtained via a facile hydrothermal method. Besides, gas sensors based on the acquired materials were fabricated to investigate their sensing performances toward triethylamine (TEA). The results reveal that the gas sensor based on In2O3/In2S3 exhibits a high response of 37 at 300 °C toward 0.45 mg/L TEA, which is 3.7 times higher than that of bare In2O3. Meanwhile, it also possesses fast response/recovery time (19 s/154 s), good repeatability, selectivity and long-term stability. The excellent sensing performances toward TEA are mainly attributed to the massive oxygen vacancy defects and heterojunction formed between In2O3 and In2S3. This work provides a facile temperature-dependent route to controllably synthesize hierarchical In2O3/In2S3 microsphere heterostructures, and the In2O3/In2S3 sensor shows great application prospects in TEA detection.

Abstract Background and objectives: Bloodstream infection (BSI) is a life-threatening condition in critically ill patients, but pathogen quantification techniques during treatment are laborious. This study aimed to explore the impact of monitoring pathogen DNA load changes and polymicrobial infection in blood by droplet digital polymerase chain reaction (ddPCR) on the prognosis of patients with BSIs. Methods This prospective case series study was conducted in the general intensive care unit of the Zhejiang Provincial People’s Hospital and included patients with BSIs from May 2020 to January 2021. Pathogens DNA load and presence of polymicrobial BSIs were dynamically monitored by ddPCR. Results Sixteen patients with BSIs proven by blood culture were recruited (87.5% men; mean age, 69.3 ± 13.7 years). All pathogens identified by blood culture were Gram-negative bacteria, among which seven were multidrug-resistant strains. The 28-day mortality rate was 62.5%. Compared to the 28-day survivors, the non-survivors were older (P = 0.04), had higher pathogen DNA load on the second (day 3–4) and third (day 6–7) ddPCR assay (P

AIM: To investigate the histological characteristics and ultrastructure of recurrent Chinese R124L mutated corneal dystrophy after keratoplasty. METHODS: The subjects were enrolled from a Chinese family of corneal dystrophy with R124L heterozygous gene mutation and with a history of consanguineous marriage. Normal corneal samples were used as controls. RESULTS: In this family, 2 patients (3 eyes) underwent penetrating keratoplasty (PKP) and 2 patients (4 eyes) underwent lamellar keratoplasty (LKP). They had recurrence at 33.5±3.0 (range 30-36)mo after keratoplasty. Among them, 1 patient (1 eye) underwent PKP again and 1 patient (2 eyes) underwent LKP again. In the R124L mutated recurrent corneal dystrophy, the corneal turbidity was mainly distributed from the upper corneal cortex to the anterior stroma; the corneal epithelium surface was rougher and more uneven; and, the corneal erosions were larger. Hematoxylin-eosin staining showed that the thickness of the corneal epithelium was uneven; the arrangement of the epithelial cells was disordered; and, some corneal epithelial cells were swollen. The results of Congo red staining, Masson's trichrome staining and Periodic acid-Schiff staining were positive, while that of Alcian blue staining was negative. Under a transmission electron microscope, deposition of high electron density substances between epithelial and basal cells, and, apoptosis of basal cells were observed. Many high electron density depositions were observed in the sub-epithelial and anterior corneal matrix. CONCLUSION: In the Chinese family of recurrent corneal dystrophy with R124L gene mutation, the corneal epithelia of the recurrent cases are rougher, and the corneal depositions are extracellular amyloid fibrin.

Abstract Background Diplozoidae are monogenean (Monogenea: Polyopisthocotylea) fish parasites characterised by a unique life history: two larvae permanently fuse into an X-shaped “Siamese” organism. Taxonomy and phylogeny of Diplozoidae and Polyopisthocotylea remain unresolved due to the unavailability of molecular markers with sufficiently high resolution. Mitogenomes may be a suitable candidate, but there are currently only 12 available for the Polyopisthocotylea (three for Diplozoidae). The only available study of diplozoid mitogenomes found unique base composition patterns and elevated evolution rates in comparison with other Monogenean mitogenomes. Methods To further explore their evolution and generate molecular data for evolutionary studies, we sequenced the complete mitogenomes of two Diplozoidae species, Paradiplozoon homoion and Paradiplozoon yarkandense, and conducted a number of comparative mitogenomic analyses with other polyopisthocotyleans. Results We found further evidence that mitogenomes of Diplozoidae evolve at a unique, elevated rate, which was reflected in their exceptionally long branches, large sizes, unique base composition, skews, and very low gene sequence similarity levels between the two newly sequenced species. They also exhibited remarkably large overlaps between some genes. Phylogenetic analysis of Polyopisthocotylea resolved all major taxa as monophyletic, and Mazocraeidea was split into two major clades: (Diplozoidae) + (all four remaining families: Diclidophoridae, Chauhaneidae, Mazocraeidae and Microcotylidae). It also provided further confirmation that the genus Paradiplozoon is paraphyletic and requires a taxonomic revision, so the two species may have to be renamed Indodiplozoon homoion and Diplozoon yarkandense comb. nov. Conclusions Although our findings indicate that mitogenomes may be a promising tool for resolving the phylogeny of Polyopisthocotylea, elevated evolutionary rates of Diplozoidae may cause phylogenetic artefacts, so future studies should pay caution to this problem. Furthermore, as the reason for their elevated evolution remains unknown, Diplozoidae are a remarkably interesting lineage for other types of evolutionary mitogenomic studies. Graphical Abstract

INTRODUCTION: Defects in the human solute carrier family 26 member 4 (SLC26A4) gene are reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify SLC26A4 mutations in Chinese patients with CH and analyze the function of the mutations. METHODS: Patients with primary CH were screened for 21 CH candidate genes mutations by targeted next-generation sequencing. All the exons and exon-intron boundaries of SLC26A4 were identified and analyzed. The function of six missense mutation in SLC26A4 were further investigated in vitro. RESULTS: Among 273 patients with CH, seven distinct SLC26A4 heterozygous mutations (p.S49R, p.I363L, p.R409H, p.T485M, p.D661E, p.H723R, c.919-2A>G) were identified in 10 patients (3.66%, 10/273). In vitro experiments showed that mutation p.I363L, p.R409H, p.H723R affect the membrane location and ion transport of SLC26A4, while p.S49R did not. Mutation p.T485M and p.D661E only affected ion transport, but had no effect on the membrane location. DISCUSSION AND CONCLUSION: The prevalence of SLC26A4 mutations was 3.66% in Chinese patients with CH. Five mutations (p.I363L, p.R409H, p.T485M, p.D661E and p.H723R) impaired the membrane location or ion transport function of SLC26A4, suggesting important roles for Ile363, Arg409, Thr485, Asp661, and His723 residues in SLC26A4 function. As all variants identified were heterozygous, the pathogenesis of these patients cannot be explained, and the pathogenesis of these patients needs further study

Triangular silver nanoplates exhibit excellent optical and catalytic properties in many fields, such as catalysts, sensors and bio-medicine. In this paper, triangular nanoplates were generated just in the presence of sodium citrate through a light-induced ripening process, which were converted from spherical silver nanoparticles by reducing silver nitrate with sodium borohydride. By using UV–Vis spectroscopy, particle size analyzer, transmission electron microscopy (TEM) and Ag+ concentration analysis, the effects of precursors during the preparation of triangular nanoplates were systematically investigated and the optimal experimental conditions were determined. Based on density functional theory (DFT), the adsorption energies of citrate ion, malate ion and tartronate ion on Ag (111), (110) and (100) were calculated. In addition, theoretical calculations coupled with experimental observations showed that citrate ion as capping agent could more preferentially bind to Ag (111) and thus blocked Ag (111) while only allowing extensive growth along the lateral direction. This well explains sodium citrate is an efficient agent in preparing triangular silver nanoplates.

The study aimed to observe the therapeutic effect of static progressive stretching (SPS) combined with extracorporeal shock wave therapy (ESWT) on extension knee joint contracture in rats and the effect on the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway in the development of joint capsule fibrosis. Thirty-six Sprague Dawley rats were randomly divided into blank control group, immobilization model group, natural recovery group, ESWT intervention group, SPS intervention group, and SPS combined with ESWT intervention group. The left knee joints of the rats, except for the control group, were fixed with an external fixation brace for four weeks at full extension to form joint contractures. The therapeutic effect of each intervention was assessed by evaluating total and arthrogenic contracture, the number of total cells and collagen deposition in the anterior joint capsule, the protein levels of TGF-β1, FGF-2, and ERK2 in the anterior joint capsule, the mean optical density of upstream RAS and downstream ERK2 positive expression in the MAPK/ERK pathway. SPS in combination with ESWT was more effective in relieving joint contracture, improving the histopathological changes in the anterior joint capsule, and suppressing the high expression of target proteins and the overactivated MAPK/ERK pathway. The overactivated MAPK/ERK pathway was involved in the formation of extension knee joint contracture in rats. SPS in combination with ESWT was effective in relieving joint contracture and fibrosis of joint capsule. Moreover, the inhibition of the overactivated MAPK/ERK pathway may be the potential molecular mechanism for its therapeutic effect.

In small and medium-sized mountainous rivers, there are usually hydropower stations in upper reaches as well as widened and heightened river sections in downstream reaches that are close to settlements. The environmental flow (EF) ensures river connectivity and the survival of aquatic organisms. The Tennant and wetted perimeter methods were used to calculate the minimum EF, and the R2CROSS criteria were used to evaluate the rationality of hydraulic parameters. The result shows that downstream areas with large cross-sections may suffer from shallow water depths, insufficient wetted perimeters, and poor overall connectivity of the water bodies, even under the standard EF discharges. A novel method was proposed to ensure EF and sustain suitable hydraulic conditions. The minimum EF calculated by the Tennant method is adopted as the design flow, and a small trapezoidal trough channel is excavated on the wide riverbed of an artificial river section. The width and depth of the small channel are calculated with Manning's equation. As a study case, this method was applied in the Fenglingang River in Zhejiang Province of China. A trapezoidal groove with a depth of 0.74 m and a bottom width of 0.52 m was excavated in the center of Fenglingang River to sustain EF and maintain river connectivity. This small channel not only prevents the river from cutoff, but also enables the water depth and wetted perimeter to meet the demand of aquatic organisms.

BackgroundISL LIM homeobox 2, also known as insulin gene enhancer protein ISL-2 (ISL2), is a transcription factor gene that participates in a wide range of developmental events. However, the role of ISL2 in the hypothalamus-pituitary-thyroid axis is largely unknown. In the present study, we characterized the expression patterns of ISL2 and revealed its regulative role during embryogenesis using zebrafish.MethodsWe used the CRISPR/Cas9 system to successfully establish homozygous ISL2-orthologue (isl2a and isl2b) knockout zebrafish. Moreover, we utilized these knockout zebrafish to analyze the pituitary and thyroid phenotypes in vivo. For further molecular characterization, in situ hybridization and immunofluorescence were performed.ResultsThe isl2a mutant zebrafish presented with thyroid hypoplasia, reduced whole-body levels of thyroid hormones, increased early mortality, gender imbalance, and morphological retardation during maturity. Additionally, thyrotropes, a pituitary cell type, was notably decreased during development. Importantly, the transcriptional levels of pituitary-thyroid axis hormones-encoding genes, such as tshba, cga, and tg, were significantly decreased in isl2a mutants. Finally, the thyroid dysplasia in isl2a mutant larvae may be attributed to a reduction in proliferation rather than changes in apoptosis.ConclusionsIn summary, isl2a regulates the transcriptional levels of marker genes in hypothalamus-pituitary-thyroid axis, and isl2a knockout causing low thyroid hormone levels in zebrafish. Thus, isl2a identified by the present study, is a novel regulator for pituitary cell differentiation in zebrafish, resulting in thyroid gland hypoplasia and phenotypes of hypothyroidism.

IntroductionCirculating plasma cells (CPC) have been reported to be one of the indicators of high-risk multiple myeloma (MM), yet the prognostic significance of CPC in Chinese population and the genetic mechanisms underlying CPC formation have not been fully elucidated.MethodsPatients with newly diagnosed MM were included in this study. We used multi-parameter flow cytometry (MFC) for CPC quantification and next-generation sequencing (NGS) technology for mutational landscape mapping to identify the correlation of CPC level with clinical characteristics and the mutations.ResultsA total of 301 patients were enrolled in this investigation. We demonstrated that CPC quantification could effectively mirror the tumor load, and CPC ≥ 0.105% at diagnosis or detectable CPC after therapy indicates poor treatment response and adverse outcome, and the introduction of CPC into the R-ISS enables a more accurate risk stratification. Interestingly, we noticed an elevated percentage of light-chain MM in patients with higher CPC. Mutational landscape revealed that patients harboring mutations in TP53, BRAF, DNMT3A, TENT5C, and IL-6/JAK/STAT3 pathway-related genes tended to have higher CPC levels. Gene enrichment analysis demonstrated that pathways involving chromosome regulation and adhesion may be potential mechanisms accounting for CPC formation.DiscussionAccordingly, quantification of CPC may provide a less-invasive and reliable approach for identifying high-risk MM in Chinese population.

BackgroundExtramedullary plasmacytoma (EMP) is a localized plasma cell neoplasm that originates from tissues other than bone. The survival trends and prognostic factors of patients with EMP in recent years remain unreported.MethodsWe used the SEER databases to extract the data. Survival curves were calculated using the Kaplan-Meier method and a nomogram was created based on the Cox’s proportional hazards model.ResultsA total of 1676 cases of EMP were identified. Patients in period-2 (2008-2016) show similar survival (p=0.8624) to those in period-1(1975-2007). Age, gender, race, and sites were prognostic of patient outcomes. And the use of surgery was associated with improved survival. The patients were randomly assigned to the training cohort and the validation cohort in a ratio of 2:1. Four factors including age, gender, race, and sites were identified to be independently predictive of the overall survival of patients with EMP. A prognostic model (EMP prognostic index, EMP-PI) comprising these four factors was constructed. Within the training cohort, three risk groups displayed significantly different 10-year survival rates: low-risk (73.0%, [95%CI 66.9-78.2]), intermediate-risk (39.3%, [95%CI 34.3-44.3]), and high-risk (22.6%, [95%CI 15.3-30.9]) (p