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Abstract Maxillofacial bone defects can severely impact quality of life by impairing physiological functions such as chewing, breathing, swallowing, and pronunciation. Polyether ether ketone (PEEK) is commonly used for the repair of maxillofacial defects due to its mechanical adaptability, while its osteogenic properties still need refinement. Herein, we have utilized the piezoelectric effect exhibited by barium titanate (BTO) under low-intensity pulsed ultrasound (LIPUS) to develop an ultrasound responsive PEEK (PDA@BTO-SPEEK, PBSP) through the mediating effect of polydopamine (PDA), for repairing maxillofacial bone defects. After modification by PDA@BTO, PBSP possesses better hydrophilicity, which is conducive to cell growth and adhesion. Simultaneously, by virtue of the piezoelectric characteristics of BTO, PBSP obtains a piezoelectric coefficient that matches the bone cortex. Notably, when PBSP is stimulated by LIPUS, it can generate stable electricity and effectively accelerate the osteogenic differentiation of osteoblasts through the regulation of the Piezo1-induced calcium (Ca2+) influx and Akt/GSK3β/β-catenin pathway. In addition, PBSP presents satisfactory therapeutic effects in rat skull defect models, and its osteogenic efficiency can be further improved under LIPUS stimulation with high tissue penetration. Collectively, PBSP + LIPUS exhibits great potential as a promising alternative strategy for the repair of maxillofacial bone defects.

Abstract Objective This study aims to analyze the molecular characteristics of the novel coronavirus (SARS-CoV-2) Omicron variant BA.2.76 in Jining City, China. Methods Whole-genome sequencing was performed on 87 cases of SARS-CoV-2 infection. Evolutionary trees were constructed using bioinformatics software to analyze sequence homology, variant sites, N-glycosylation sites, and phosphorylation sites. Results All 87 SARS-CoV-2 whole-genome sequences were classified under the evolutionary branch of the Omicron variant BA.2.76. Their similarity to the reference strain Wuhan-Hu-1 ranged from 99.72 to 99.74%. In comparison to the reference strain Wuhan-Hu-1, the 87 sequences exhibited 77–84 nucleotide differences and 27 nucleotide deletions. A total of 69 amino acid variant sites, 9 amino acid deletions, and 1 stop codon mutation were identified across 18 proteins. Among them, the spike (S) protein exhibited the highest number of variant sites, and the ORF8 protein showed a Q27 stop mutation. Multiple proteins displayed variations in glycosylation and phosphorylation sites. Conclusion SARS-CoV-2 continues to evolve, giving rise to new strains with enhanced transmission, stronger immune evasion capabilities, and reduced pathogenicity. The application of high-throughput sequencing technologies in the epidemic prevention and control of COVID-19 provides crucial insights into the evolutionary and variant characteristics of the virus at the genomic level, thereby holding significant implications for the prevention and control of the COVID-19 pandemic.

Abstract Premature ovarian insufficiency (POI) is a clinically heterogeneous disease that may seriously affect the physical and mental health of women of reproductive age. POI primarily manifests as ovarian function decline and endocrine disorders in women prior to age 40 and is an established cause of female infertility. It is crucial to elucidate the causative factors of POI, not only to expand the understanding of ovarian physiology, but also to provide genetic counselling and fertility guidance to affected patients. Factors leading to POI are multifaceted with genetic factors accounting for 7% to 30%. In recent years, an increasing number of DNA damage-repair-related genes have been linked with the occurrence of POI. Among them, DNA double-strand breaks (DSBs), one of the most damaging to DNA, and its main repair methods including homologous recombination (HR) and non-homologous end joining (NHEJ) are of particular interest. Numerous genes are known to be involved in the regulation of programmed DSB formation and damage repair. The abnormal expression of several genes have been shown to trigger defects in the overall repair pathway and induce POI and other diseases. This review summarises the DSB-related genes that may contribute to the development of POI and their potential regulatory mechanisms, which will help to further establish role of DSB in the pathogenesis of POI and provide theoretical guidance for the study of the pathogenesis and clinical treatment of this disease.

Abstract Background Root system architecture (RSA), which is determined by the crown root angle (CRA), crown root diameter (CRD), and crown root number (CRN), is an important factor affecting the ability of plants to obtain nutrients and water from the soil. However, the genetic mechanisms regulating crown root traits in the field remain unclear. Methods In this study, the CRA, CRD, and CRN of 316 diverse maize inbred lines were analysed in three field trials. Substantial phenotypic variations were observed for the three crown root traits in all environments. A genome-wide association study was conducted using two single-locus methods (GLM and MLM) and three multi-locus methods (FarmCPU, FASTmrMLM, and FASTmrEMMA) with 140,421 SNP. Results A total of 38 QTL including 126 SNPs were detected for CRA, CRD, and CRN. Additionally, 113 candidate genes within 50 kb of the significant SNPs were identified. Combining the gene annotation information and the expression profiles, 3 genes including GRMZM2G141205 (IAA), GRMZM2G138511 (HSP) and GRMZM2G175910 (cytokinin-O-glucosyltransferase) were selected as potentially candidate genes related to crown root development. Moreover, GRMZM2G141205, encoding an AUX/IAA transcriptional regulator, was resequenced in all tested lines. Five variants were identified as significantly associated with CRN in different environments. Four haplotypes were detected based on these significant variants, and Hap1 has more CRN. Conclusions These findings may be useful for clarifying the genetic basis of maize root system architecture. Furthermore, the identified candidate genes and variants may be relevant for breeding new maize varieties with root traits suitable for diverse environmental conditions.

Abstract Background The waterborne pathogens Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi and Cyclospora cayetanensis can cause intestinal diseases in humans. An understanding of their occurrence and transport in the environment is essential for accurate quantitative microbial risk assessment. Methods A total of 238 influent samples were collected from four wastewater treatment plants (WWTPs) and 88 samples from eight sewer locations in Guangzhou, China. PCR-based tools were used to detect and genetically characterize Cryptosporidium spp., G. duodenalis and E. bieneusi. Eimeria spp. and Cyclospora spp. were also analyzed to assess the sources of Cryptosporidium spp., G. duodenalis and E. bieneusi in wastewater. Results The overall occurrence rates in the WWTP and sewer samples were 14.3% (34/238) and 13.6% (12/88) for Cryptosporidium spp., 55.5% (132/238) and 33.0% (29/88) for G. duodenalis, 56.3% (134/238) and 26.1% (23/88) for E. bieneusi and 45.4% (108/238) and 47.7% (42/88) for Eimeria spp., respectively. Altogether, 11 Cryptosporidium species and genotypes, six G. duodenalis genotypes, 11 E. bieneusi genotypes and four C. cayetanensis were found, together with the presence of nine Eimeria species. The common occurrence of Cryptosporidium rat genotype IV, C. muris and Eimeria papillata and E. nieschulzi suggested that rodents were significant sources of the enteric pathogens detected in the wastewater samples. Conclusions While the dominant Cryptosporidium spp. detected in the raw wastewater sampled in this study are not pathogenic to humans, the widely detected G. duodenalis assemblage A and E. bieneusi genotypes D and Type IV are well-known zoonotic pathogens. Further studies are needed to monitor the occurrence of these waterborne pathogens in WWTPs to better understand their transmission and environmental transport in China.

Abstract Background Cryptosporidium is a key genus of parasitic protists that infect humans and other vertebrates (mammals and birds). Birds are typically infected with C. avium, C. baileyi, C. galli and/or C. meleagridis, the latter of which is recognised as being zoonotic. Stimulated by the previous finding of C. meleagridis subtypes IIIbA21G1R1, IIIbA22G1R1 and IIIbA26G1R1 in diarrhoeic children in Wuhan city and environs in Hubei Province, China, we performed a molecular epidemiological survey to explore whether these or similar subtypes might occur in farmed chickens in this province. Methods PCR-coupled sequencing analyses of regions in the small subunit (SSU) of the nuclear ribosomal RNA and 60 kDa glycoprotein (gp60) genes were utilised to characterise Cryptosporidium in faecal samples from chickens (n = 471) from 14 farms from six distinct regions in Hubei Province. Results Cryptosporidium baileyi (33/471; 7.0%) and C. meleagridis (15/471; 3.2%) were identified in chickens on eight farms in five of the six distinct geographical regions. No significant age-associated difference in the prevalence of C. baileyi was evident, whereas the prevalence of C. meleagridis was significantly higher in younger (≤ 4 months) than in older chickens (> 4 months). For C. meleagridis, two subtype families, IIIb and IIIe, were defined; some of the subtypes (i.e. IIIbA26G1R1b and IIIbA22G1R1c) characterised here matched those identified previously in diarrhoeic children in Wuhan. Conclusions This is the first molecular study reporting the genetic identity and prevalence of C. baileyi and C. meleagridis in chickens in Hubei. The findings suggest that C. meleagridis subtypes IIIbA26G1R1b and IIIbA22G1R1c are cross-transmissible between chickens and humans, raising awareness about the significance of birds as potential reservoirs of zoonotic variants of Cryptosporidium. Future studies might focus on investigating the prevalence of ‘zoonotic’ subtypes of Cryptosporidium meleagridis in various species of wild and domesticated birds, and on comparing them with those found in humans in China and other countries.

Abstract Background All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. Methods Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry. Pharmaceutical or genetic inhibition of autophagy involved were carried by 3- methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Differences between two values were tested by Student’s unpaired t test. Results We show that resveratrol-induced apoptosis occurs through both the intrinsic and extrinsic apoptotic pathways. Mitochondrial membrane potential and apoptosis-related markers, such as an increased Bax/Bcl-2 ratio, and cleaved forms of caspase-8 and caspase-3, arise following resveratrol addition. Moreover, we find that resveratrol increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, and further demonstrate that resveratrol-induced autophagy depends on the LKB1-AMPK-mTOR pathway. We next reveal that some apoptosis-related markers induced by resveratrol are further attenuated by the inhibition of autophagy with 3-methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Conclusions These results suggest that resveratrol induced apoptotic cell death of HL-60 cells depends on the autophagy activated through both the LKB1-AMPK and PI3K/AKT-regulated mTOR signaling pathways.

Abstract Background The protistan pathogens Cryptosporidium and Giardia can cause significant intestinal diseases in animals and humans. Cattle, particularly calves, carrying these protists can be significant reservoirs for human infections and disease. However, little is known about the genetic make-up of Cryptosporidium and Giardia populations in cattle and other ruminants in some regions of China. Results In the present study, PCR-based tools were used to genetically characterise these protists in faecal samples from a total of 339 pre- and post-weaned calves from four distinct locations in Hubei Province using markers in the large (LSU) or small (SSU) subunits of nuclear ribosomal RNA genes. Cryptosporidium andersoni, C. bovis, C. ryanae and Giardia duodenalis assemblage E were detected in 0.6%, 10.9%, 4.1% and 22.6% of calves, respectively. Conclusions This study is the first to report the prevalence of Cryptosporidium and Giardia in pre- and post-weaned calves in Hubei Province, and encourages large-scale molecular studies of animals and humans, in an effort to better understand the epidemiology of these enteric pathogens in China.

Abstract Background Preference-based measures of health-related quality of life (HRQoL), such as the EQ-5D or the SF-6D, are essential for health economic evaluation. However, they are rarely included in clinical trials of ankylosing spondylitis (AS). This study aims to develop mapping algorithms to predict EQ-5D-3L and EQ-5D-5L health utility scores from the Bath Ankylosing Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). Methods Patients with AS were recruited from the largest tertiary hospital in Shandong province, China, between December 2019 and October 2020. Patients were selected by convenience sampling method according to the following criteria: (1) diagnosed with AS according to the New York criteria; (2) aged 18 years and above; and (3) without mental disorders; (4) able to understand the questionnaires; (5) without serious complications. There were 243 patients who completed the face-to-face questionnaire survey, and 5 cases with missing values in key variables were excluded. Ordinary least squares, censored least absolute deviations, Tobit, adjusted limited dependent variable mixture model and beta-mixture model (BM) in the direct approach and ordered logit and multinomial logit (Mlogit) model in the response approach were used to develop mapping algorithms. Mean absolute error, root mean square error, Spearman’s correlation coefficient and concordance correlation coefficient were used to access predictive performance. Results The 238 patients with AS had a mean age of 35.19 (SD = 9.59) years, and the majority (74.47%) were male. The observed EQ-5D-3L and EQ-5D-5L health utility values were 0.88 (SD = 0.12) and 0.74 (SD = 0.27), respectively. The EQ-5D-5L had higher conceptual overlap with the BASDAI and BASFI than the EQ-5D-3L did. The Mlogit was the best-performing model for the EQ-5D-3L, and the BM showed better performance in predicting EQ-5D-5L than other direct and indirect mapping models did. Conclusion This study demonstrates that the EQ-5D-5L, rather than EQ-5D-3L, should be selected as the target outcome measure of HRQoL in patients with AS in China, and the BM mapping algorithm could be used to predict EQ-5D-5L values from BASDAI and BASFI for health economic evaluation.

Abstract Background While ondansetron (OND) is widespread availability, the contribution of OND to improve patient outcomes among intensive care unit (ICU) patients has not been examined. This study aimed to illustrate the association between early OND use and in-hospital mortality in critically ill patients and investigate whether this association differed according to OND dose. Methods The MIMIC-IV database was employed to identify patients who had and had not received OND. Statistical approaches included multivariate logistic regression, propensity score matching (PSM), and propensity score-based inverse probability of treatment weighting (IPTW) models to ensure the robustness of our findings. Results In total, 51,342 ICU patients were included. A significant benefit in terms of in-hospital mortality was observed in the OND patients compared to the non-OND group in the early stage [odds ratio (OR) = 0.75, 95% CI 0.63–0.89, p

Abstract Background COVID-19 pandemic has forced physicians to quickly determine the patient’s condition and choose treatment strategies. This study aimed to build and validate a simple tool that can quickly predict the deterioration and survival of COVID-19 patients. Methods A total of 351 COVID-19 patients admitted to the Third People’s Hospital of Yichang between 9 January to 25 March 2020 were retrospectively analyzed. Patients were randomly grouped into training (n = 246) or a validation (n = 105) dataset. Risk factors associated with deterioration were identified using univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression. The factors were then incorporated into the nomogram. Kaplan-Meier analysis was used to compare the survival of patients between the low- and high-risk groups divided by the cut-off point. Results The least absolute shrinkage and selection operator (LASSO) regression was used to construct the nomogram via four parameters (white blood cells, C-reactive protein, lymphocyte≥0.8 × 109/L, and lactate dehydrogenase ≥400 U/L). The nomogram showed good discriminative performance with the area under the receiver operating characteristic (AUROC) of 0.945 (95% confidence interval: 0.91–0.98), and good calibration (P = 0.539). Besides, the nomogram showed good discrimination performance and good calibration in the validation and total cohorts (AUROC = 0.979 and AUROC = 0.954, respectively). Decision curve analysis demonstrated that the model had clinical application value. Kaplan-Meier analysis illustrated that low-risk patients had a significantly higher 8-week survival rate than those in the high-risk group (100% vs 71.41% and P