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Manganese (Mn) is an essential microelement for broiler breeding and its deficiency causes tibial dyschondroplasia (TD). Tibial growth plate (TGP) development and metaphyseal vascularization are crucial for tibia growth in fast-growing broiler chickens, but their roles in Mn deficiency-induced TD in chicks remain unclear. This study was designed to clarify this issue. A total of 36 one-day-old broilers were divided into the control group and Mn-deficiency (Mn-D) group, which were fed with a standard diet (60 mg Mn/kg) and Mn deficiency diet (22 mg Mn/kg) for 42 days, respectively. TGP and proximal tibial metaphysis were collected to perform the related assays. This study found that Mn deficiency decreased the tibia length and TGP thickness in the TD model. Also, Mn deficiency increased the irregular and white tibial dyschondroplasia lesions (TDL) region under the TGP, and reduced the expression levels of vascular endothelial growth factor (VEGF) and macrophage migration inhibitory factor (MIF). Combined with histological assessment, it was suggested that Manganese deficiency inhibited angiogenesis in the proximal tibial metaphysis. Meanwhile, Mn deficiency enhanced the expression levels of hypoxia-inducible factor-1 α (HIF-1α), autophagy-related protein 5 (ATG5), and microtubule-associated protein 1 light chain 3 β (LC3-II) in TGP, but decreased the expression level of SQSTM1 (P62), which suggested that autophagy was activated during this process. Collectively, these data indicate that HIF-1α up-regulation and concurrent autophagy activation exert a protective effect against Mn deficiency-induced angiogenesis inhibition, which may provide useful guidance to prevent TD in broilers.

Dysphagia is one of the most common complications of anterior cervical spine surgery. Local steroid was widely used to reduce the postoperative swallowing pain. However, the effect of local steroid application on dysphagia after anterior cervical spine surgery was still uncertain.We searched Medline (PubMed), Embase and the Cochrane Library on July 27, 2021 for studies investigating the effect of local steroid application on dysphagia after anterior cervical spine surgery from their date of inception to 2021. The relative risk or weighted mean difference with 95% confidence interval was recorded as a summary statistic consist of postoperative dysphagia, swallowing VAS scores, SWAL-QOL scores, PSTSI, and steroid related complications.This meta-analysis included 7 RCT studies involving 254 patients in the steroid group and 232 patients in the placebo group. Results showed local steroid group had less patients with dysphagia, lower swallowing VAS scores and less severe of prevertebral soft-tissue edema on the fourth day after surgery. No significant difference in non-fusion rate between the two groups was observed. And all included studies had no serious steroid related complications reported.The use of local steroid in anterior cervical spine surgery could reduce the early postoperative dysphagia without serious steroid related complication. However, the safety of local steroid application still need further studies with larger samples.

Background and Aims Development of a prophylactic hepatitis C virus (HCV) vaccine will require accurate and reproducible measurement of neutralizing breadth of vaccine-induced antibodies. Currently available HCV panels may not adequately represent the genetic and antigenic diversity of circulating HCV strains, and the lack of standardization of these panels makes it difficult to compare neutralization results obtained in different studies. Here, we describe the selection and validation of a genetically and antigenically diverse reference panel of 15 HCV pseudoparticles (HCVpp) for neutralization assays. Methods We chose 75 envelope (E1E2) clones to maximize representation of natural polymorphisms observed in circulating HCV isolates, and 65 of these clones generated functional HCVpp. Neutralization sensitivity of these HCVpp varied widely. HCVpp clustered into 15 distinct groups based on patterns of relative sensitivity to seven broadly neutralizing monoclonal antibodies (bNAbs). We used these data to select a final panel of 15 antigenically representative HCVpp. Results Both the 65 and 15 HCVpp panels span four tiers of neutralization sensitivity, and neutralizing breadth measurements for seven bNAbs were nearly equivalent using either panel. Differences in neutralization sensitivity between HCVpp were independent of genetic distances between E1E2 clones. Conclusions Neutralizing breadth of HCV antibodies should be defined using viruses spanning multiple tiers of neutralization sensitivity, rather than panels selected solely for genetic diversity. We propose that this multi-tier reference panel could be adopted as a standard for the measurement of neutralizing antibody potency and breadth, facilitating meaningful comparisons of neutralization results from vaccine studies in different laboratories.

In this paper, the well-known graduated cylindrical shell (GCS) model is slightly revised by introducing longitudinal and latitudinal deflections of prominences originating from active regions (ARs). Subsequently, it is applied to the three-dimensional (3D) reconstruction of an eruptive prominence in AR 13110, which produced an M1.7 class flare and a fast coronal mass ejection (CME) on 2022 September 23. It is revealed that the prominence undergoes acceleration from $\sim$246 to $\sim$708 km s$^{-1}$. Meanwhile, the prominence experiences southward deflection by 15$\degr$$\pm$1$\degr$ without longitudinal deflection, suggesting that the prominence erupts non-radially. Southward deflections of the prominence and associated CME are consistent, validating the results of fitting using the revised GCS model. Besides, the true speed of the CME is calculated to be 1637$\pm$15 km s$^{-1}$, which is $\sim$2.3 times higher than that of prominence. This is indicative of continuing acceleration of the prominence during which flare magnetic reconnection reaches maximum beneath the erupting prominence. Hence, the reconstruction using the revised GCS model could successfully track a prominence in its early phase of evolution, including acceleration and deflection., Comment: 13 pages, 8 figures, accepted for publication in RAA

Manganese (Mn) is an essential trace element for broiler chickens; its deficiency causes tibial dyschondroplasia (TD) characterized by lameness and growth retardation. Inorganic and organic manganese sources are used in global poultry production, but there is a lack of systematic investigations to compare the bioavailability among them. In this study, 120 1-day-old Arbor Acres (AA) broilers were randomly divided into four groups (n = 30), i.e., control group (Mn sulfate, 60 mg/kg), Mn-D group (Mn deficiency, 22 mg/kg), Mn-Gly group (Mn glycinate, 60 mg/kg), and Mn-Pro group (Mn proteinate, 60 mg/kg). During the 42-day experiment, growth performance, tibial bone parameters, pathological index changes, serum biochemical changes, and oxidative stress indicators were evaluated. These results not only suggested that Mn plays a crucial role in the normal development of tibia and the maintenance of redox homeostasis in broilers, but also proved that organic Mn supplementation, especially Mn proteinate, improved the tibia development and the absorption efficiency, as well as overall oxidative stress status of broilers, suggesting that it had greater bioavailability than inorganic Mn. Thus, application of organic Mn source may be an effective way to reduce economic losses and resolve animal welfare concerns due to TD in commercial poultry farming.

Manganese (Mn) is an essential trace element for bone growth, and its deficiency has been shown to increase the incidence of leg abnormalities in fast-growing broilers, such as tibial dyschondroplasia (TD). Proliferation and differentiation of growth plate chondrocyte are critical for tibia development, but their roles in Mn deficiency-induced TD remains to be elucidated. Thirty 1-day-old Arbor Acres chicks were randomly divided into two groups and fed with control diet (60 mg Mn/kg diet) and Mn-deficiency diet (22 mg Mn/kg diet) for 42 days, respectively. Mn deficiency-induced TD model was successfully established and samples from proximal tibia metaphysis and growth plate were collected for assays. Pathological observation showed that Mn deficiency induced morphological abnormality and irregular arrangement of chondrocytes in proliferative and hypertrophic zone of tibial growth plate. Also, Mn deficiency decreased mRNA and protein expression levels of type II collagen and type X collagen in tibial growth plate, indicating the impairment of proliferating and hypertrophic chondrocytes. Moreover, down-regulated gene expression levels of Sox9, Tgf-β, Ihh, Runx2, Mef2c and Bmp-2 were shown in tibial growth plate of Mn-deficiency group, demonstrating that Mn deficiency inhibited the transcription levels of key regulators to disrupt chondrocyte proliferation and differentiation. Collectively, these findings confirmed that Mn deficiency affected the proliferation and differentiation of chondrocytes in tibial growth plate via inhibiting related regulatory factors, leading to TD in broilers.

Manganese (Mn) is a crucial trace element for poultry nutrition, and its deficiency compromises tibial cartilage development, leading to perosis and a higher incidence of slipped tendon. Tibial dyschondroplasia (TD) is a metabolic cartilage disease characterized by disruption of endochondral bone formation, which is closely related to extracellular matrix (ECM) degradation, in which Mn deficiency plays an important role. Previous studies have confirmed the role of matrix metalloproteinases (MMPs) in the pathogenesis of TD, but whether dysregulated ECM degradation and MMP expression profiles in growth plate are involved in Mn deficiency-induced avian TD has not been fully elucidated yet. Thus, this study was conducted to clarify these issues. Firstly, we successfully established TD model induced by Mn deficiency in broiler chicks. Mn deficiency decreased the number of chondrocytes, contents of proteoglycan, and type II collagen in tibial growth plate, demonstrating the tibial growth plate damage with enhanced ECM degradation. Also, Mn deficiency inhibited the Nrf2 signaling pathway and enhanced the protein levels of NLRP3, active caspase-1, and active IL-1β in tibial growth plate, indicating the oxidative stress and inflammatory response in Mn deficiency-induced TD. Additionally, upregulated expression levels of MMPs (MMP1, 9, and 13) were observed in tibial growth plate of Mn deficiency group. In summary, these findings suggest that Mn deficiency-enhanced ECM degradation is involved in avian TD, which may be correlated with oxidative stress, inflammatory response, and upregulation of MMPs.

Highly c-axis textured β-silicon nitride (β-Si3N4) ceramic with fine grains was prepared by a new method of hot extrusion for the first time. The (002) pole figure on the section plane vertical to extruding direction showed a characteristic of center rotational symmetry. The average cline angle between elongated β-Si3N4 grains and hot extruding direction was about 14.4°. The degree of c-axis texturing by hot extrusion was comparable to that achieved by rotating magnetic field. The hardness and toughness anisotropy in different direction was apparent and relatively higher hardness was achieved in the present work mainly due to the finer grain size. Therefore, many different compositions of c-axis aligned Si3N4-based ceramics with tailored mechanical properties could be achieved by the strategy of hot extrusion.

The standard recommended and common reconstruction method for spinal tuberculosis is titanium mesh bone graft and autogenous iliac crest. However, these methods have their own disadvantages.To evaluate the clinical efficacy of one-stage posterior debridement with iliac bone graft, titanium mesh bone graft, or nanohydroxyapatite/polyamide-66 cage in thoracic and lumbar tuberculosis.Between January 2013 and December 2018, 57 patients with thoracic or lumbar tuberculosis were treated by interbody bone graft combined with posterior internal fixation after debridement. Thirteen patients were treated with iliac bone graft to construct the stability of the vertebral body, 26 patients were treated with titanium mesh bone graft, and 18 patients were treated with nanohydroxyapatite/polyamide-66 cage bone graft. The main clinical results were evaluated by intervertebral height, cage subsidence, operation time, operative blood loss, postoperative hospitalization, postoperative complications, visual analog scale (VAS) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American Spinal Injury Association (ASIA) grade, and bone graft fusion time. All the outcomes were recorded and analyzed by statistical methods.The mean follow-up time was 24.5 months. Neurologic function was improved in most patients at the last follow-up. There were significant differences in ESR, CRP, and VAS score between preoperative and postoperative values; however, there were no significant differences in ESR, CRP, and VAS score among the three groups. There were no significant differences in operation time, blood loss, postoperative hospitalization, and postoperative complications among the three groups at discharge. There was no significant difference in ASIA grade among the three groups at the last follow-up. Nanohydroxyapatite/polyamide-66 cage group had a lower cage subsidence (P = 0.013). The bone graft fusion time of the nanohydroxyapatite/polyamide-66 cage group was significantly shorter than the iliac bone graft group and the titanium mesh bone graft (P0.05).The follow-up outcomes showed that the method involving one-stage posterior debridement and internal fixation, interbody graft, and fusion is an effective and safe surgical method for patients with thoracic and lumbar tuberculosis. The incidence rate of cage subsidence was less and the bone graft fusion time was shorter with nanohydroxyap atite/polyamide 66 cage when compared with iliac bone graft and titanium mesh bone graft in the surgical treatment of thoracic and lumbar tuberculosis. Nanohydroxyapatite/polyamide-66 cage has a promising application prospect to be a new bone graft material.

Background: Planting halophytes is an efficient way of remediating saline soils, but with undetermined consequences for the soil microbial communities and functioning of the soil ecosystem. Here, we investigated how halophyte-mediated reclamation influences soil microbial diversity and how changes in microbial networks may subsequently alter soil functioning during five years of phytoremediation on saline soils. Results: Phytoremediation increasedthe overall microbial diversity and enriched specific microbialgroups such as Gammaproteobacteria,Chloroflexi, and Gemmatimonadetes, and some known halophilic bacteria like Marinobacter and Halomonas. In contrast, other microbial groups such as Firmicutes, Betaproteobacteria,Basidiomycota and Zygomycota decreased in the phytoremediated soils. Network analysis showed positive associations between the taxa richness of a core network module and soil functional genes associated with nutrient cycling. The genomes clustered with taxa in modules indicated that taxa within core module had higher gene copies of essential functional genes associated with carbon, and nitrogen cycling. These taxa, including Rhodobacteraceae,Hyphomicrobiaceae, Nocardioidaceae and Acidobacteria-6, were also associated with potential nitrifying bacteria, nitrogen fixers, and decomposers. In addition, the reclaimed soil supported higher taxa richness of core module, which yielded greater soil multifunctionality. Conclusions: Our work highlights microbial taxa within network module strongly correlated with soil functioning during phytoremediation. Furthermore, our study also suggests that while there was no change in the overall soil salinity level, phytoremediation increased soil multifunctionality by enhancing the microbial diversity and altering specific groups of the soil microbiome, suggesting a sign of successful reclamation.

BackgroundTuberculosis is a communicable disease that is a major cause of ill health. Bibliometrics is an important statistical methodology used to analyze articles and other publications in the literature study. In this study, publications on molecular epidemiology were analyzed using bibliometric analysis. The statistical analysis of influential publications, journals, countries and authors was first conducted.MethodsThe Web of Science database was searched for publications on the molecular epidemiology of tuberculosis with the keywords “tuberculosis” and “molecular epidemiology” in the title. The number of publications, citation analysis, co-authorship of the author, institution and country, keyword co-occurrence, and reference co-citations were analyzed.ResultsA total of 225 journal articles were retrieved. The mean citation was 37.72 per article and 292.69 per year. The annual publications on molecular epidemiology fluctuated within a certain range in the past. Journal of Clinical Microbiology is the most published journal with 33 articles. RASTOGI N is the most prolific author with 11 articles. The top 1 research institution is Inst Pasteur Guadeloupe. Stratified by the number of publications, the USA was the most prolific country. It also cooperates closely with other countries. Burstness analysis of references and keywords showed that the developing research trends in this field mainly focused on “genetic diversity” and “lineage” during the past decade.ConclusionThe annual publications on tuberculosis molecular epidemiology fluctuated within a specific range in the past decade. The USA continues to dominate research output and funding. The exchange of expertise, ideas, and technology is of paramount importance in this field. More frequent and deeper cooperation among countries or institutions will be essential in the future.

Summary The purpose of this study is to conduct a meta-analysis to evaluate the efficacy of screening and decolonization protocol for Staphylococcus aureus (SA) in total joint arthroplasty (TJA). We systematically searched the electronic databases of PubMed, Embase and Cochrane databases for relevant literatures from January 2000 to September 2020. The outcomes were colonization rate, total-surgical site infection (SSI) rate, SA-SSI rate and methicillin-resistant Staphylococcus aureus (MRSA)-SSI rate. All calculations and statistical tests were performed using Stata 14.0 software. A total of 12 studies were eligible in this study. Compared with control group, the screening and decolonization group had lower risks in total-SSI (risk ratio (RR) = 0.52; 95% confidence interval (CI): 0.40–0.67), SA-SSI (RR = 0.48; 95% CI: 0.32–0.72) and MRSA-SSI (RR = 0.45; 95% CI: 0.21–0.96). The nasal SA colonization was found to be associated with higher accidences of SSI involving total-SSI (RR = 1.49; 95% CI: 1.02–2.18), SA-SSI (RR = 2.51; 95% CI: 0.97–6.50) and MRSA-SSI (RR = 7.84; 95% CI: 1.67–36.79). The colonization rate of SA was significantly reduced after decolonization. No difference was observed between universal decolonization and screening-based decolonization. In conclusion, colonization of SA is associated with increased risk of SSI in TJA. Screening and decolonization protocol are proven to be effective to reduce colonization of SA and present protective effects against SSI in TJA. Moreover, universal decolonization protocol is non-inferior to screening-based decolonization.

Objectives: The aim of this study was to define the risk factors affecting the prognosis of patients with acute traumatic spinal cord injury (tSCI), and to discuss the value of prognostic nutritional index (PNI) and controlling nutritional status (COUNT) score in predicting the prognosis of patients with acute tSCI.Methods: We retrospectively analyzed the clinical data of 75 patients with acute tSCI. The optimal cutoff value was obtained through the receiver operating characteristic curve (ROC), and the value of PNI and COUNT score were 45.05 and 3.5 respectively. Patients were divided into high PNI groups and low PNI groups, high COUNT groups and low COUNT groups respectively based on cutoff values. The differences of outcome indexes such as American spinal injury association impairment scale (AIS), exercise score, Bathel index score and light touch score were analyzed, and the prognostic factors of tSCI patients were analyzed. A improved outcome was defined as improvement of AIS grade ≥ 1.Results: Compared with the improvement group, the non-improvement group had lower serum albumin and PNI, higher COUNT score, longer hospital stay and higher postoperative infection rate (P < 0.05). PNI and COUNT score were closely related to the AIS grade (r = 0.629, P < 0.001; r = -0.855, P < 0.001). After adjusting for confounding factors, the odds ratios of PNI and COUNT score for predicting improved outcomes in patients with acute tSCI were 1.396 (95%CI: 1.141-1.709） and 0.284 (95%CI: 0.136-0.0.594）, respectively. The area under the curve (AUC) of PNI and count scores for predicting improved outcomes were 0.752 (95% CI: 0.641 ~ 0.862, P < 0.001) and 0.766 (95% CI: 0.654 ~ 0.879, P < 0.001), respectively. Conclusion: PNI and count scores may be independent predictors of improved outcomes in patients with acute tSCI.

Current findings suggest that minimally percutaneous endoscopic lumbar discectomy (PELD) is a practical therapeutic approach for lumbar disc herniation (LDH). However, some patients still end up with residual low back pain, even after surgery. Our study aims to construct and validate a nomogram to predict residual low back pain after PELD.The medical records of 355 LDH patients admitted to the author's hospital were retrospectively analyzed between January 2019 and December 2021. The patients were randomly divided into two groups with a ratio of 7:3, namely a modelling group and a validation group. The univariable logistics and multivariable regression methods were used to screen the independent risk factors. A nomogram was then drawn using independent risk factors selected from the univariable and multivariable regression analyses. The concordance index (C-index), the receiver operating characteristic (ROC) curve, the calibration curve, and the decision curve analysis were used to evaluate the nomogram's performance. Finally, the accuracy of the nomogram was verified by a validation cohort.36.6% (130/355) of patients showed low back pain after percutaneous endoscopic lumbar discectomy, while 63.4% (225/355) showed no symptoms. Multivariable logistical regression analysis showed that Modic change (p 0.05, OR = 1.813), fatty infiltration of the paravertebral muscle (p 0.05, OR = 2.935), and edema of lumbodorsal fascia (p = 0.049, OR = 1.611) were significant risk factors for post-operative residual back pain. Moreover, the C-index of the predictive nomogram was 0.743 (0.681-0.805), the area under the receiver operating characteristic curve (AUC) value was 0.739, and the DCA results exhibit a net benefit between 0.16 and 0.66. The above internal validation methods demonstrate the nomogram's good predictive capability.Each variable in the model had a quantitatively corresponding risk score, which can be used in predicting residual low back pain after PELD.

Background and objectives: For patients with inoperable non-small cell lung cancer, concurrent chemoradiotherapy is the mainstay of treatment. At present, TMN stage is still the most commonly used clinical prediction model, but in the real world, patients with the same stage receive the same mode of treatment, their survival will be significantly different. The aim of our study was to look for predictors of patient survival in addition to TMN staging. If all kinds of predictors can be combined, the survival prediction of patients can be greatly improved and the clinical treatment and medication can be guided.Methods：The survival differences of 147 lung cancer patients receiving concurrent chemoradiotherapy were analyzed. Univariate and multivariate COX regression analysis were used to explore the relationship between blood markers before treatment and patient survival.Results: Univariate COX regression analysis showed that gender, hemoglobin, MCV, NLR, Smoking Index，IL-6 and SUA/SCr were significantly correlated with survival in patients receiving concurrent chemoradiotherapy. Multivariate COX regression analysis showed that IL-6 and SUA/SCr were prognostic factors for patients receiving radiotherapy and chemotherapy. According to receiver operating characteristic (ROC) curve analysis, the AUC of SUA/SCr and IL-6 were 0.757 and 0.770, respectively, and the optimal cutoff points of SUA/SCr and IL-6 were 3.99 and 4.79, respectively.Conclusions：Our study shows that gender, hemoglobin, MCV, NLR, Smoking Index，SUA/SCr and IL-6 are related to survival of lung cancer patients. Il-6 and SUA/SCr are effective predictors of survival in lung cancer patients.

Glyphosate (Gly) is a globally spread herbicide that can cause toxic injuries to hepatocytes. Dietary trehalose (Tre) exerts cytoprotective effect in numerous liver diseases through anti-oxidant and anti-inflammatory properties. However, it is yet to be investigated whether Tre affords protection against Gly-induced hepatotoxicity. To evaluate the negative effect of Gly in liver and assess the possible protective role of Tre, sixty Hy-line Brown roosters were allocated into three groups: the first group presented the control with a normal diet, the second group fed normal feed containing 200mg/kg Gly, and the third group fed normal feed containing 200 mg/kg Gly and 5 g/kg Tre. Plasma and liver tissues were collected and analyzed after 120 days. Firstly, Gly-elevated serum levels of hepatic injury markers and liver histopathological damages were evidently alleviated by Tre administration. Also, Tre normalized Gly-altered serum and hepatic lipid profiles and Oil Red O-stained lipid levels, suggesting the improvement of hepatic steatosis. The severely accumulated malondialdehyde levels and impaired antioxidant status in Gly-exposed roosters were markedly improved by administration with Tre. Simultaneously, Gly-inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) level and consequent reduced levels of Nrf2-downstream targets in liver were markedly normalized by Tre treatment. Additionally, Tre treatment evidently mitigated Gly-induced inflammasome response via inhibiting NLRP3 inflammasome activation. Overall, these observations provide novel insights that the protective action of Tre against Gly-induced hepatic steatosis is attributed to activation of Nrf2 pathway and inhibition of NLRP3 inflammasome activation.

IntroductionBreast milk is recognised as the best natural food for neonates, but many women experience postpartum hypogalactia (PH). Randomised trials have found that acupuncture exert therapeutic effect on women with PH. However, systematic reviews on the efficacy and safety of acupuncture are still lacking; therefore, this systematic review aims to evaluate the efficacy and safety of acupuncture for PH.Methods and analysisEight English databases (PubMed, Cochrane Library, MEDLINE, EMBASE, EBSCO, Scopus, Ovid, Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Wan-Fang, Chinese Biomedical Literature, Chinese Scientific Journal) will be systematically searched from their establishment to 1 September 2022. Randomised controlled trials (RCTs) of the efficacy of acupuncture for PH will be reviewed. The study selection, data extraction, and research quality evaluation will be conducted independently by two reviewers. The primary outcome is the change in serum prolactin level from baseline to the end of treatment. Secondary results include milk secretion volume, total effectiveness rate, degree of mammary fullness, rate of exclusive breastfeeding, infant weight gain, and adverse events. A meta-analysis will be performed using RevMan V.5.4 statistical software. Otherwise, a descriptive analysis will be conducted. The risk of bias will be assessed using the revised Cochrane risk-of-bias tool.Ethics and disseminationThis systematic review protocol does not require ethical approval because it does not include private information/data of the participants. This article will be published in peer-reviewed journals.PROSPERO registration numberCRD42022351849Strengths and limitations of this studyThis study will be the first systematic review to evaluate the efficacy and safety of acupuncture for PH by including available clinical trials that have been published in the past.The quality of the included trials will be assessed using the Revised Cochrane Risk of Bias Tool (RoB2) for Randomised Trials.This study will provide more reliable evidence for clinical management because most RCTs on acupuncture for PH have small sample sizes.This study will include only English and Chinese trials, which may lead to missing studies in other languages.

RecD family helicases play an important role in prokaryotic genome stability and serve as the structural models for studying superfamily 1B (SF1B) helicases. However, RecD-catalyzed duplex DNA unwinding behavior and the underlying mechanism are still elusive. RecD family helicases share a common proto-helicase with eukaryotic Pif1 family helicases, which are well known for their outstanding G-quadruplex (G4) unwinding ability. However, there are still controversial points as to whether and how RecD helicases unfold G4 structures. Here, single-molecule fluorescence resonance energy transfer (smFRET) and magnetic tweezers (MT) were used to study Deinococcus radiodurans RecD2 (DrRecD2)-mediated duplex DNA unwinding and resolution of G4 structures. A symmetric, repetitive unwinding phenomenon was observed on duplex DNA, revealed from the strand switch and translocation of one monomer. Furthermore, we found that DrRecD2 was able to unwind both parallel and antiparallel G4 structures without obvious topological preferences. Surprisingly, the unwinding properties of RecD on duplex and G4 DNA are different from those of Pif1. The findings provide an example, in which the patterns of two molecules derived from a common ancestor deviate during evolution, and they are of significance for understanding the unwinding mechanism and function of SF1B helicases.

Mercuric chloride (HgCl

ObjectiveThis study aimed to compare postoperative outcomes in surgical and patient-reported outcomes (PROs) between percutaneous endoscopic lumbar interbody fusion (PE-LIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of lumbar spinal stenosis (LSS).MethodsWe reviewed a total of 89 patients undergoing single-level surgery for lumbar spinal stenosis from January 2018 to July 2021. The cases were categorized as PE-LIF (Group PE-LIF, 41 cases) or MIS-TLIF (Group MIS-TLIF, 48 cases) approach. Parameters obtained at baseline through at least six months of follow-up were collected. The surgical outcomes involving the operative time, estimated blood loss, postoperative bed staying time, and length of hospital stays were analyzed. PROs included the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), modified MacNab standard evaluation, intervertebral fusion rate, and postoperative complications.ResultsA total of 89 patients were included in this analysis involving 41 patients who underwent PE-LIF and 48 patients who underwent MIS-TLIF. The 2 groups were similar in gender, age, body mass index, follow-up time and surgery levels (P > 0.05), and were not significantly different in the length of hospital stays (P > 0.05). PE-LIF had a significantly longer operative time, greater fluoroscopy time, lower estimated blood loss and shorter bed rest time than MIS-TLIF. Both groups improved significantly from baseline for the VAS and ODI scores. PE-LIF was associated with a lower VAS score for back pain at three-day after surgery. There were no significant differences between PE-LIF and MIS-TLIF in the excellent or good rates and intervertebral fusion rates at the last follow-up (P > 0.05). As for related complications, there were no significant complications occurred, and no significant differences were seen in the complications between both groups (P > 0.05).ConclusionsTo summarize, PE-LIF and MIS-TLIF are both safe and effective for LSS. PE-LIF has a definite short-term curative effect with less trauma.

Significance Hepatitis C virus chronically infects approximately 1% of the world’s population, making an effective vaccine for hepatitis C virus a major unmet public health need. The membrane-associated E1E2 envelope glycoprotein has been used in clinical studies as a vaccine candidate. However, limited neutralization breadth and difficulty in producing large amounts of homogeneous membrane-associated E1E2 have hampered efforts to develop an E1E2-based vaccine. Our previous work described the design and biochemical validation of a native-like soluble secreted form of E1E2 (sE1E2). Here, we describe the immunogenic characterization of the sE1E2 complex. sE1E2 elicited broadly neutralizing antibodies in immunized mice, with increased neutralization breadth relative to the membrane-associated E1E2, thereby validating this platform as a promising model system for vaccine development.

Objectives of this study were to evaluate the alleviating effects of a commercial beta-1,3-glucan product (Aleta, containing 50% beta-1,3-glucan, Kemin Industries) on metabolic stress in transition Holstein cows as reflected by circulating metabolites and enzymes. Fifty-four multiparous Holstein cows were randomly allocated to three groups with 18 cows each. Cows in each group received a commercial basal diet or the basal diet supplemented with Aleta calculated to supply 5 or 10 g of Aleta per cow per day. Blood samples were collected at day −21, 1, and 21 relative to calving for determination of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) , high density lipoprotein cholesterol (HDL C) , very low density lipoprotein (VLDL), glucose, insulin, β-hydroxybutyric acid (BHBA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), and non-esterified fatty acid (NEFA). Supplementation with Aleta markedly elevated serum concentrations of TG, TC, HDL C, LDL-C and VLDL, implying its positive effect on lipid metabolism in transition dairy cows. Aleta treatment significantly decreased the serum concentrations of NEFA and BHBA, but markedly elevated the serum concentrations of glucose and insulin. Also, Aleta treatment significantly elevated the dry matter intake and milk production in postpartum cows, indicating the alleviating effect of Aleta on negative energy balance in transition cows. Moreover, Aleta treatment significantly reduced the serum activities of AST, ALT and GGT, indicating its hepatoprotective effect on transition cows. These results suggest that Aleta supplementation may help to improve fat metabolism disorder initiated by negative energy balance in transition dairy cows.

In Orchidaceae, pollination is mostly animal-mediated, and one-third of species have evolved a deceptive pollination mechanism without rewards. Cypripedium is a representative lineage of nonrewarding orchids restricted to temperate regions. Cypripedium subtropicum flowers are pollinated by hoverflies and have hairy tufts that visually resemble an aphid colony covered with honey dew. We recorded the behavior of hoverflies on the flowers, determined the breeding system of the species and the structure of hairy tufts, and investigated the roles of hairy tufts and floral volatiles in this specialized pollination by using pollination experiments, scanning electron microscopy, bioassays and chemical analyses. The white hairy tufts covering the sidelobes of the labellum provide edible rewards and serve as crucial visual lures for hoverflies. The flowers emit primarily (E)-β-farnesene and a smaller amount of β-pinene that were found to attract hoverflies. Our results suggest that C. subtropicum uses both visual mimicry of an aphid-colonized labellum with a reward and chemical mimicry of aphid alarm pheromones to attract hoverflies for pollination. This is the first described example of a rewarding mimicry system in plants, where the models are animals with their secretions and the reward is similar in nutrients to that of the model mimicked.

Highly undercooled solidification experiments were carried out by melt purification combined with cyclic superheating method on Au-12 wt.%Ge eutectic alloy. The solidification structures of Au-12 wt.%Ge eutectic alloy under different undercoolings were also analyzed by using the scanning electron microscope (SEM). The experimental results revealed that the maximum undercooling could reach up to 102 K. The microstructure analysis showed that the coarse bulk eutectic existed in the solidification structure when the undercooling was less than 34 K. When the undercooling was larger than 34 K and less than 56 K, the solidification structure transformed into cellular eutectic. The coarse primary (α-Au) phase precipitated from the undercooled alloy melt when the undercooling was larger than 56 K. The volume fraction of the primary (α-Au) phase gradually increased with the increase of undercooling. In this paper, a method to regulate the solidification structure of Au-12 wt.%Ge eutectic alloy is proposed, which provides a new way to improve the solidification structure and has important guiding significance for the processing and forming process of Au-12 wt.%Ge eutectic alloy.

This study aims at evaluating the effects of RTS (rotation softened trauma fixation system) compared with PCPSF (percutaneous conventional pedicle screw fixation) on type A thoracolumbar fractures. In this retrospective cohort study, 116 patients with type A thoracolumbar fractures from March 2014 to June 2018 were enrolled. PCPSF was performed in 60 patients, meanwhile the other 56 patients accepted RTS. VAS scores, Cobb angle, anterior vertebral height (AVH) and perioperative data were compared between the two groups. Both groups were consistent with baseline on demographic and clinical characteristics. No significant difference was observed in VAS score between-group before and after operation. One year after surgery, the VAS score of RTS group was lower than that of PCPSF group (0.7 ± 0.3 vs. 1.5 ± 0.4). The postoperative AVH (%) in PCPSF was 82.3% (95%CI, 81.7–84.6), and 91.78% (95% CI, 91.1–92.4) in RTS. The postoperative improvement rate of AVH (%) in RTS was higher than that in PCPSF (30.6 ± 5.0 [95% CI, 29.2–32.0] vs. 22.0 ± 7.3 [95% CI, 20.2–24.2]). The postoperative Cobb angle (°) in PCPSF was 2.6 ± 3.4 (95%CI,11.7–13.5), and 7.5 ± 2.0 (95%CI,7.0–8.0) in RTS. The postoperative correction of Cobb angle (°) in RTS was higher than that in PCPSF (16.1 ± 3.8 95%CI,15.1–17.1] vs. 11.6 ± 5.2 95%CI,10.3–13.1]). Compared with PCPSF, RTS has advantages in restoring the anterior vertebral height and reducing local kyphosis.

Manganese (Mn) is an essential microelement for broiler breeding and its deficiency causes tibial dyschondroplasia (TD). Tibial growth plate (TGP) development and metaphyseal vascularization are crucial for tibia growth in fast-growing broiler chickens, but their roles in Mn deficiency-induced TD in chicks remains unclear. This study was designed to clarify this issue. A total of 36 one-day-old broilers were divided into the control group and Mn-deficiency (Mn-D) group, which were fed with a standard diet (60 mg Mn/kg) and Mn deficiency diet (22 mg Mn/kg) for 42 days, respectively. TGP and proximal tibial metaphysis were collected to perform the related assays. First, Mn deficiency decreased the tibia length and TGP thickness in TD model. Mn deficiency reduced the number of blood vessels in proximal tibial metaphysis by histological analysis. Also, Mn deficiency decreased the mRNA and protein expression levels of vascular endothelial growth factor (VEGF) and macrophage migration inhibitory factor (MIF) in TGP. Moreover, up-regulation of hypoxia-inducible factor-1 alpha (HIF-1α) at both mRNA and protein levels was found in TGP of Mn-D group, suggesting the antagonistic role of HIF-1α against angiogenesis inhibition. Additionally, Mn deficiency enhanced the autophagy related 5 (ATG5) and microtubule associated protein 1 light chain 3 beta (LC3-II) expression levels, but decreased the SQSTM1 (p62) expression levels in TGP, suggesting autophagy activation in this process. Collectively, these data indicate that HIF-1α up-regulation and concurrent autophagy activation exert the protective effect against Mn deficiency-induced angiogenesis inhibition, which may provide a useful guidance to prevent TD in broilers.

Supplemental material, sj-pdf-2-imr-10.1177_03000605221086146 for Airway foreign body caused by pepper inhalation 7 years previously retrieved under conscious sedation with spontaneous respiration: a case report by Wei Lei, Zhen-yong Gan, Yong-feng Liang, Cai-xia Liang, Cang-zheng Jin, Wei-ping Peng, Xin-cai Qiu and Hai-yan Guo in Journal of International Medical Research

Supplemental material, sj-pdf-1-imr-10.1177_03000605221086146 for Airway foreign body caused by pepper inhalation 7 years previously retrieved under conscious sedation with spontaneous respiration: a case report by Wei Lei, Zhen-yong Gan, Yong-feng Liang, Cai-xia Liang, Cang-zheng Jin, Wei-ping Peng, Xin-cai Qiu and Hai-yan Guo in Journal of International Medical Research

With the gradual completion of the human genome project, proteomes have gained extremely important value in the fields of human disease and biological process research. In our previous research, we performed transcriptomic analyses of longissimus dorsi tissue from Kazakh cattle and Xinjiang brown cattle and conducted in-depth studies on the muscles of both species through epigenetics. However, it is unclear whether differentially expressed proteins in Kazakh cattle and Xinjiang brown cattle regulate muscle production and development. In this study, a proteomic analysis was performed on Xinjiang brown cattle and Kazakh cattle by using TMT markers, HPLC classification, LC/MS and bioinformatics analysis. A total of 13,078 peptides were identified, including 11,258 unique peptides. We identified a total of 1874 proteins, among which 1565 were quantifiable. Compared to Kazakh cattle, Xinjiang brown cattle exhibited 75 upregulated proteins and 44 downregulated proteins. These differentially expressed proteins were enriched for the functions of adrenergic signaling in cardiomyocytes, fatty acid degradation and glutathione metabolism. In our research, we found differentially expressed proteins in longissimus dorsi tissue between Kazakh cattle and Xinjiang brown cattle. We predict that these proteins regulate muscle production and development through select enriched signaling pathways. This study provides novel insights into the roles of proteomes in cattle genetics and breeding.

Mercury (Hg) is a persistent environmental and industrial pollutant that accumulated in the body and induces oxidative stress and inflammation damage. Selenium (Se) has been reported to antagonize immune organs damage caused by heavy metals. Here, we aimed to investigate the prevent effect of Se on mercuric chloride (HgCl

Background Triple-negative breast cancer (TNBC) is the most aggressive subtype and occurs in approximately 15–20% of diagnosed breast cancers. TNBC is characterized by its highly metastatic and recurrent features, as well as a lack of specific targets and targeted therapeutics. Epidermal growth factor receptor (EGFR) is highly expressed in a variety of tumors, especially in TNBC. LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory. This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action. Methods LR004-VC-MMAE was prepared by coupling a cytotoxic payload (MMAE) to an anti-EGFR antibody (LR004) via a linker, and the drug-to-antibody ratio (DAR) was analyzed by HIC-HPLC. The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset (GSE41313) and Western blotting. MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE (0, 0.0066, 0.066, 0.66, 6.6 nmol/L), and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation. The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VC-MMAE concentrations (2.5 and 5 nmol/L) with wound healing and Transwell invasion assays. Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells in MDA-MB-468 and MDA-MB-231 cells. The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo. Briefly, BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDA-MB-231 cells. Then they were randomly divided into 4 groups (n = 6 per group) and treated with PBS, naked LR004 (10 mg/kg), LR004-VC-MMAE (10 mg/kg), or doxorubicin, respectively. Tumor sizes and the body weights of mice were measured every 4 days. The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR, ERK, MEK phosphorylation and tumor stemness marker gene expression. Results LR004-VC-MMAE with a DAR of 4.02 were obtained. The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells (P 50 values of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were (0.13 ± 0.02) nmol/L and (0.66 ± 0.06) nmol/L, respectively, which were significantly lower than that of cells treated with MMAE [(3.20 ± 0.60) nmol/L, P P 2/M phase in MDA-MB-468 [(34 ± 5)% vs. (12 ± 2)%, P P Conclusions LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes. It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC.

Glyphosate (GLY), one of the most extensively used herbicides in the world, has been shown to inhibit testosterone synthesis in male animals. Mitochondria are crucial organelles for testosterone synthesis and its dysfunction has been demonstrated to induce the inhibition of testosterone biosynthesis. However, whether low-dose GLY exposure targets mitochondria to inhibit testosterone synthesis and its underlying mechanism remains unclear. Here, an in vitro model of 10 μM GLY-exposed mouse Leydig (TM3) cells was established to elucidate this issue. Data firstly showed that mitochondrial malfunction, mainly manifested by ultrastructure damage, disturbance of mitochondrial dynamics and mitochondrial reactive oxygen species (mtROS) overproduction, was responsible for GLY-decreased protein levels of steroidogenic enzymes, which leads to the inhibition of testosterone synthesis. Enhancement of autophagic flux and activation of mitophagy were shown in GLY-treated TM3 cells, and further studies have revealed that GLY-activated mitophagy is parkin-dependent. Notably, GLY-inhibited testosterone production was significantly improved by parkin knockdown. Finally, data showed that treatment with mitochondria-targeted antioxidant Mito-TEMPO (M-T) markedly reversed GLY-induced mitochondrial network fragmentation, activation of parkin-dependent mitophagy and consultant testosterone reduction. Overall, these findings demonstrate that GLY induces mtROS overproduction to activate parkin-dependent mitophagy, which contributes to the inhibition of testosterone synthesis. This study provides a potential mechanistic explanation for how GLY inhibits testosterone synthesis in mouse Leydig cells.