Search

Abstract Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.

Abstract To date, only one polymer can self-grow to an extended length beyond its original size at room temperature without external stimuli or energy input. This breakthrough paves the way for significant advancements in untethered autonomous soft robotics, eliminating the need for the energy input or external stimuli required by all existing soft robotics systems. However, only freshly prepared samples in an initial state can self-grow, while non-fresh ones cannot. The necessity of synthesizing from monomers for each use imposes significant limitations on practical applications. Here, we propose a strategy to rejuvenate non-fresh samples to their initial state for on-demand self-growth through the synergistic effects of solvents and dynamic covalent bonds during swelling. The solvent used for swelling physically transforms the non-fresh LCEs from the liquid crystal phase to the isotropic phase. Simultaneously, the introduction of the transesterification catalyst through swelling facilitates topological rearrangements through exchange reactions of dynamic covalent bonds. The rejuvenation process can also erase growth history, be repeated several times, and be regulated by selective swelling. This strategy provides a post-modulation method for the rejuvenation and reuse of self-growing LCEs, promising to offer high-performance materials for cutting-edge soft growing robotics.

Abstract Diabetic cardiomyopathy (DCM) is a chronic disease caused by diabetes mellitus, which is recognized as a worldwide challenging disease. This study aimed to investigate the role and the potential mechanism of knocking down the NACHT-, LRR- and PYD domains-containing protein 3 (NLRP3), an inflammasome associated with onset and progression of various diseases, on high glucose or diabetes -induced cardiac cells pyroptosis and ferroptosis, two regulated non-necrosis cell death modalities discovered recent years. In the present study, both in vivo and in vitro studies were conducted simultaneously. Diabetic rats were induced by 55 mg/kg intraperitoneal injection of streptozotocin (STZ). Following the intraperitoneal injection of MCC950 (10 mg/kg), On the other hand, the DCM model in H9C2 cardiac cells was simulated with 35 mmol/L glucose and a short hairpin RNA vector of NLRP3 were transfected to cells. The results showed that in vivo study, myocardial fibers were loosely arranged and showed inflammatory cell infiltration, mitochondrial cristae were broken and the GSDMD-NT expression was found notably increased in the DM group, while the protein expressions of xCT and GPX4 was significantly decreased, both of which were reversed by MCC950. High glucose reduced the cell viability and ATP level in vitro, accompanied by an increase in LDH release. All of the above indicators were reversed after NLRP3 knockdown compared with the HG treated alone. Moreover, the protein expressions of pyroptosis- and ferroptosis-related fators were significantly decreased or increased, consistent with the results shown by immunofluorescence. Furthermore, the protective effects of NLRP3 knockdown against HG were reversed following the mtROS agonist rotenone (ROT) treatment. In conclusion, inhibition of NLRP3 suppressed DM-induced myocardial injury. Promotion of mitochondrial ROS abolished the protective effect of knockdown NLRP3, and induced the happening of pyroptosis and ferroptosis. These findings may present a novel therapeutic underlying mechanism for clinical diabetes-induced myocardial injury treatment.

Summary: Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.

This is an article in the field of mining engineering. Ca2+ and Mg2+ are easily dissolved from fluorapatite and dolomite in the acid medium of reverse flotation, and there is a "cumulative effect" in the process of backwater circulation, which has an adverse effect on the flotation indexes. Taking fluorapatite, dolomite and quartz as the research objects, the effect of different recycle times of backwater on the flotation recovery of three single minerals was studied. The results showed that when pH value was 5, the recovery difference between dolomite and fluorapatite decreased from 72.21% to 64.19%, and the recovery of quartz maintained at about 10%; When the number of cycles reached 5, the recovery difference between dolomite and fluorapatite slightly increased to 69.74%, and the recovery of quartz slightly decreased to 11.22%. In this study, the mechanism of dissolved ions in backwater for three kinds of single minerals was revealed by measuring the number of dissolved ions, zeta potential of mineral surface and ions adsorption capacity of mineral surface under backwater circulation system.

Objective The aim of this study was to investigate the impact of dietary nicotinic acid (NA) on apparent nutrient digestibility, rumen fermentation, and rumen microbiota in uncastrated Xiangzhong black cattle. Methods Twenty-one uncastrated Xiangzhong black cattle (385.08±15.20 kg) aged 1.5 years were randomly assigned to the control group (CL, 0 mg/kg NA in concentrate diet), NA1 group (800 mg/kg NA in concentrate diet) and NA2 group (1,200 mg/kg NA in concentrate diet). All animals were fed a 60% concentrate diet and 40% dried rice straw for a 120-day feeding experiment. Results Supplemental NA not only enhanced the apparent nutrient digestibility of acid detergent fiber (p

ABSTRACTNeutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

Summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein continues to evolve antigenically, impacting antibody immunity. D1F6, an affinity-matured non-stereotypic VH1-2 antibody isolated from a patient infected with the SARS-CoV-2 ancestral strain, effectively neutralizes most Omicron variants tested, including XBB.1.5. We identify that D1F6 in the immunoglobulin G (IgG) form is able to overcome the effect of most Omicron mutations through its avidity-enhanced multivalent S-trimer binding. Cryo-electron microscopy (cryo-EM) and biochemical analyses show that three simultaneous epitope mutations are generally needed to substantially disrupt the multivalent S-trimer binding by D1F6 IgG. Antigenic mutations at spike positions 346, 444, and 445, which appeared in the latest variants, have little effect on D1F6 binding individually. However, these mutations are able to act synergistically with earlier Omicron mutations to impair neutralization by affecting the interaction between D1F6 IgG and the S-trimer. These results provide insight into the mechanism by which accumulated antigenic mutations facilitate evasion of affinity-matured antibodies.

Formononetin (FMNT) is a secondary metabolite of flavonoids abundant in legumes and graminaceous plants such as Astragalus mongholicus Bunge [Fabaceae; Astragali radix] and Avena sativa L. [Poaceae]. Astragalus is traditionally used in Asia countries such as China, Korea and Mongolia to treat inflammatory diseases, immune disorders and cancers. In recent years, inflammation and oxidative stress have been found to be associated with many diseases. A large number of pharmacological studies have shown that FMNT, an important bioactive metabolite of Astragalus, has a profoundly anti-inflammatory and antioxidant potential. This review focuses on providing comprehensive and up-to-date findings on the efficacy of the molecular targets and mechanisms involve of FMNT and its derivatives against inflammation and oxidative stress in both in vitro and in vivo. Relevant literature on FMNT against inflammation and oxidative stress between 2013 and 2023 were analyzed. FMNT has antioxidant and anti-inflammatory potential and shows mild or no toxicity in various diseases. Moreover, in the medical field, FMNT has shown potential in the prevention and treatment of cancers, neurological diseases, fibrotic diseases, allergic diseases, metabolic diseases, cardiovascular diseases, gastrointestinal diseases and autoimmune diseases. Thus, it is expected to be utilized in more products in the medical, food and cosmetic industries in the future.

Abstract Background Declined skeletal muscle mass and function are inevitable consequences of long‐term diabetes and bring about many adverse events. Muscle fibre atrophy and interstitial fibrosis are major pathological manifestations of diabetic sarcopenia. Stimulator of interferon genes (STING) participates in various metabolic diseases. We aimed to explore whether and how STING regulates the above pathological manifestations of diabetic sarcopenia. Methods Wild‐type and STINGgt/gt C57BL/6J mice and C2C12 myotubes were used to study the role of STING in the regulation of diabetic sarcopenia and the underlying mechanisms. Results STING was abnormally activated in diabetic muscles and in PA‐treated myotubes (P

Abstract Due to the pressure of the ecological environment and government, it is incumbent for enterprises to undertake corporate social responsibility (CSR). However, during the recycling process, awareness of equity concerns due to the distribution of benefits among members has intensified, and it is crucial to resolve channel conflicts and design a reasonable cooperation model to recycle used power batteries. Therefore, this paper constructs a closed-loop supply chain composed of power battery manufacturer, retailer and third-party collector based on the consideration of cascade utilization, in order to study the impact of the level of CSR and the degree of fairness concern on the decision-making of channel participants. Our research shows that: (1) Fairness concern behavior adversely affects the supply chain, which raises the sales price and reduces the collecting rate and the utility of the supply chain as a whole. (2) Undertaking CSR is beneficial to the development of the power battery market, and also helps to reduce the sense of unfairness among third-party recycling companies. (3) The cost-sharing contract effectively coordinates the distribution of supply chain benefits and improves the recycling rate. Finally, we further verify the correctness of the conclusions through numerical studies.

Abstract Background Minimizing mortality losses due to multiple stress and obtaining maximum performance are the production goals for newly received cattle. In recent years, vaccination and metaphylaxis treatment significantly decreased the mortality rate of newly received cattle, while the growth block induced by treatment is still obvious. Assessment of blood metabolites and behavior monitoring offer potential for early identification of morbid animals. Moreover, the ruminal microorganisms’ homeostasis is a guarantee of beef steers’ growth and health. The most critical period for newly received cattle is the first-month post-transport. Therefore, analyzing rumen metagenomics, rumen metabolomics, host metabolomics, and their interaction during receiving period (1 day before transport and at days 1/4, 16, and 30 after transport) is key to revealing the mechanism of growth retardation, and then to formulating management and nutritional practices for newly received cattle. Results The levels of serum hormones (COR and ACTH), and pro-inflammatory factors (IL-1β, TNF-α, and IL-6) were highest at day 16, and lowest at day 30 after arrival. Meanwhile, the antioxidant capacity (SOD, GSH-Px, and T-AOC) was significantly decreased at day 16 and increased at day 30 after arrival. Metagenomics analysis revealed that rumen microbes, bacteria, archaea, and eukaryota had different trends among the four different time points. At day 16 post-transport, cattle had a higher abundance of ruminal bacteria and archaea than those before transport, but the eukaryote abundance was highest at day 30 post-transport. Before transport, most bacteria were mainly involved in polysaccharides digestion. At day 4 post-transport, the most significantly enriched KEGG pathways were nucleotide metabolism (pyrimidine metabolism and purine metabolism). At day 16 post-transport, the energy metabolism (glycolysis/gluconeogenesis, pyruvate metabolism) and ruminal contents of MCP and VFAs were significantly increased, but at the same time, energy loss induced by methane yields (Methanobrevibacter) together with pathogenic bacteria (Saccharopolyspora rectivirgula) were also significantly increased. At this time, the most upregulated ruminal L-ornithine produces more catabolite polyamines, which cause oxidative stress to rumen microbes and their host; the most downregulated ruminal 2',3'-cAMP provided favorable growth conditions for pathogenic bacteria, and the downregulated ruminal vitamin B6 metabolism and serum PC/LysoPC disrupt immune function and inflammation reaction. At day 30 post-transport, the ruminal L-ornithine and its catabolites (mainly spermidine and 1,3-propanediamine) were decreased, and the serum PC/LysoPC and 2',3'-cNMPs pools were increased. This is also consistent with the changes in redox, inflammation, and immune status of the host. Conclusions This study provides new ideas for regulating the health and performance of newly received cattle during the receiving period. The key point is to manage the newly received cattle about day 16 post-transport, specifically to inhibit the production of methane and polyamines, and the reproduction of harmful bacteria in the rumen, therefore improving the immunity and performance of newly received cattle. Video Abstract

Mitophagy maintains tissue homeostasis by self-eliminating defective mitochondria through autophagy. How mitophagy regulates stem cell activity during hair regeneration remains unclear. Here, we found that mitophagy promotes the proliferation of hair germ (HG) cells by regulating glutathione (GSH) metabolism. First, single-cell RNA sequencing, mitochondrial probe, transmission electron microscopy, and immunofluorescence staining showed stronger mitochondrial activity and increased mitophagy-related gene especially Prohibitin 2 (Phb2) expression at early-anagen HG compared to the telogen HG. Mitochondrial inner membrane receptor protein PHB2 binds to LC3 to initiate mitophagy. Second, molecular docking and functional studies revealed that PHB2-LC3 activates mitophagy to eliminate the damaged mitochondria in HG. RNA-seq, single-cell metabolism, immunofluorescence staining, and functional validation discovered that LC3 promotes GSH metabolism to supply energy for promoting HG proliferation. Third, transcriptomics analysis and immunofluorescence staining indicated that mitophagy was down-regulated in the aged compared to young-mouse HG. Activating mitophagy and GSH pathways through small-molecule administration can reactivate HG cell proliferation followed by hair regeneration in aged hair follicles. Our findings open up a new avenue for exploring autophagy that promotes hair regeneration and emphasizes the role of the self-elimination effect of mitophagy in controlling the proliferation of HG cells by regulating GSH metabolism.

Graft healing is a complex process affected by environmental factors, with temperature being one of the most important influencing factors. Here, oriental melon grafted onto pumpkin was used to study changes in graft union formation and sugar contents at the graft interface under night temperatures of 18 °C and 28 °C. Histological analysis suggested that callus formation occurred 3 days after grafting with a night temperature of 28 °C, which was one day earlier than with a night temperature of 18 °C. Vascular reconnection with a night temperature of 28 °C was established 2 days earlier than with a night temperature of 18 °C. Additionally, nine sugars were significantly enriched in the graft union, with the contents of sucrose, trehalose, raffinose, D–glucose, D–fructose, D–galactose, and inositol initially increasing but then decreasing. Furthermore, we also found that exogenous glucose and fructose application promotes vascular reconnection. However, exogenous sucrose application did not promote vascular reconnection. Taken together, our results reveal that elevated temperatures improve the process of graft union formation through increasing the contents of sugars. This study provides information to develop strategies for improving grafting efficiency under low temperatures.

IntroductionCritical deterioration in hospitalized children, defined as ward to pediatric intensive care unit (PICU) transfer followed by mechanical ventilation (MV) or vasoactive infusion (VI) within 12 h, has been used as a primary metric to evaluate the effectiveness of clinical interventions or quality improvement initiatives. We explore the association between critical events (CEs), i.e., MV or VI events, within the first 48 h of PICU transfer from the ward or emergency department (ED) and in-hospital mortality.MethodsWe conducted a retrospective study of a cohort of PICU transfers from the ward or the ED at two tertiary-care academic hospitals. We determined the association between mortality and occurrence of CEs within 48 h of PICU transfer after adjusting for age, gender, hospital, and prior comorbidities.ResultsExperiencing a CE within 48 h of PICU transfer was associated with an increased risk of mortality [OR 12.40 (95% CI: 8.12–19.23, P

ABSTRACTAlthough changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

There is an increasing demand for simple and efficient sample delivery technology to match the rapid development of serial crystallography and its wide application in analyzing the structural dynamics of biological macromolecules. Here, a microfluidic rotating-target device is presented, capable of three-degrees-of-freedom motion, including two rotational degrees of freedom and one translational degree of freedom, for sample delivery. Lysozyme crystals were used as a test model with this device to collect serial synchrotron crystallography data and the device was found to be convenient and useful. This device enables in situ diffraction from crystals in a microfluidic channel without the need for crystal harvesting. The circular motion ensures that the delivery speed can be adjusted over a wide range, showing its good compatibility with different light sources. Moreover, the three-degrees-of-freedom motion guarantees the full utilization of crystals. Hence, sample consumption is greatly reduced, and only 0.1 mg of protein is consumed in collecting a complete dataset.

BackgroundTanzania is among the countries with the highest malaria cases and deaths worldwide, where vulnerable populations have been severely affected due to poverty and weakness in health system and infrastructure. The China-Tanzania Malaria Control Project (the Project) was a two-phase global health intervention project implemented between 2015 and 2021 that aimed to transfer project-designated intervention experience in malaria elimination to the Tanzanian health system. This study aims to identify the barriers and facilitators encountered during the Project and to improve our understanding of the emerging phenomenon of South-South global health collaboration.MethodsWe conducted thematic analysis of qualitative data collected from a purposive sample of 14 participants from multiple stakeholders including project management office, project implementation agency, funding partners and external evaluators of the Project. A conceptual framework was developed to construct the interviews guides. The interviews were transcribed verbatim, crossover checked, translated into English, and analyzed with NVivo 12.0. We conducted the open coding followed by the axial coding based on the Grounded Theory to generate themes and subthemes, and identified key influencing factors that aided or hindered the malaria control in Tanzania.ResultsThe findings suggested that malaria control strategies should largely be tailored due to varied socioeconomic contexts. The perceived enablers in practice include project-designated intervention experiences and technologies, professional and self-learning capabilities of the implementation team, sustainable financial assistance, and support from the international partners. The barriers include the shortage of global health talents, existing gaps to meet international standards, defects in internal communication mechanisms, inadequacy of intergovernmental dialogue, and limitations in logistical arrangements. A checklist and policy implications for China's future engagement in malaria control in resource-limited settings have been proposed.ConclusionsThe initiative of Health Silk Road has generated strong global interest in promoting development assistance in health. In the hope of generalizing the evidence-based interventions to high malaria-endemic countries in Africa, the need for China to carefully face the challenges of funding gaps and the lack of support from recipient governments remains ongoing. It is recommended that China should form an institutionalized scheme and sustainable funding pool to ensure the steady progress of development assistance in health.

ObjectiveThe aim of our study was to evaluate the prognostic value of gated SPECT MPI in non-obstructed coronary arteries (INOCA) patients, sought to stratify patients more accurately and thus derive more reliable prognostic information.Materials and methodsIn total, 167 patients with INOCA were enrolled. The patients were divided into two groups according to their SSS. Patients were followed-up regularly in terms of major adverse cardiovascular event (MACE), including cardiac death, nonfatal myocardial infarction, stroke, re-hospitalization with angina pectoris, and recurrent angina pectoris. Kaplan-Meier curves and Cox's proportional hazards models were used to analyze survival and identify predictive factors.ResultsAdverse cardiac events occurred in 33 cases (19.8%). The rate of MACE was higher in the summed stress score (SSS) ≥4 group than in the SSS 0–3 group (30.1% vs. 9.5%, respectively, P = 0.001) and MACE-free survival was lower (annual MACE-free rates of 87.5% vs. 96.2%, respectively, P = 0.003). Event-free survival was consistently higher in patients with normal arteries than in those with non-obstructive coronary artery disease (annual MACE-free rates of 96.1% and 88.4%, P = 0.035). When the SSS and the CAG results were combined, patients with normal coronary arteries (SSS 0–3) had the best prognosis and those with non-obstructive coronary artery stenosis (SSS ≥ 4) had the worst. However, the early prognosis of patients with non-obstructive coronary artery disease and SSS of 0–3 was comparable to that of patients with normal coronary arteries and SSS ≥ 4 (annual MACE-free rates of 100%, 94.6%, 93.1%, and 78.2%, respectively). Multivariate Cox's regression indicated that the SSS [hazard ratio (HR) = 1.126, 95% confidence interval (CI) 1.042–1.217, P = 0.003] and non-obstructive coronary artery disease (HR = 2.559, 95% CI 1.249–5.246, P = 0.01) were predictors of adverse cardiac events.ConclusionSPECT MPI data were prognostic for INOCA patients, thus identifying groups at high risk. The long-term predictive efficacy of such data exceeded that of CAG data. A combination of the two measures more accurately stratified INOCA patients in terms of risk.

Objective Endometrial carcinoma (EC) is a common malignant tumour in women. Berberin (BBR) is an alkaloid with anti-tumour activity, and circular RNA (circRNAs) has been extensively studied in cancers. However, whether BBR regulates the development of EC by regulating circular RNA zinc finger protein 608 (ZNF608) is unknown. Methods Different concentrations of BBR were used to treat endometrial cancer cells. A quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess the expression of circ_ZNF608, microRNA-377-3p (miR-377-3p) and cyclooxygenase 2 (COX2). The expression of COX2 protein was detected by western blot. The effect of circ_ZNF608 in BBR-treated EC cells was verified by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, thymidine analog 5-ethynyl-2’-deoxyuridine (EdU) assay, colony formation assay, transwell, and flow cytometry. The effect of BBR and circ_ZNF608 on tumour growth was evaluated by xenograft tumour model in vivo. Results Berberine can inhibit the proliferation and metastasis of EC cells and promote apoptosis, which is related to the concentration. Circ_ZNF608 and COX2 were abnormally increased, while the levels of miR-377-3p were reversed in EC tissues and cells. Overexpression of circ_ZNF608 can restore the inhibitory effect of BBR on EC cells. In addition, circ_ZNF608 restored the inhibitory effect of BBR on EC cells by inhibiting the expression of miR-377-3p. Similarly, MiR-377-3p/COX2 can regulate the tumour progression of EC under BBR. Finally, BBR can inhibit the growth of endometrial carcinoma in vivo. Conclusion BBR was found to inhibit EC via the circ_ZNF608/miR-377-3p/COX2 axis, which is helpful in endometrial carcinoma.

Biodiversity loss during the Anthropocene is a serious ecological challenge. Pollinators are important vectors that provide multiple essential ecosystem services but are declining rapidly in this changing world. However, several studies have argued that a high abundance of managed bee pollinators, such as honeybees (Apis mellifera), may be sufficient to provide pollination services for crop productivity, and sociological studies indicate that the majority of farmers worldwide do not recognize the contribution of wild pollinator diversity to agricultural yield. Here, we review the importance of pollinator diversity in natural and agricultural ecosystems that may be thwarted by the increase in abundance of managed pollinators such as honeybees. We also emphasize the additional roles diverse pollinator communities play in environmental safety, culture, and aesthetics. Research indicates that in natural ecosystems, pollinator diversity enhances pollination during environmental and climatic perturbations, thus alleviating pollen limitation. In agricultural ecosystems, pollinator diversity increases the quality and quantity of crop yield. Furthermore, studies indicate that many pollinator groups are useful in monitoring environmental pollution, aid in pest and disease control, and provide cultural and aesthetic value. During the uncertainties that may accompany rapid environmental changes in the Anthropocene, the conservation of pollinator diversity must expand beyond bee conservation. Similarly, the value of pollinator diversity maintenance extends beyond the provision of pollination services. Accordingly, conservation of pollinator diversity requires an interdisciplinary approach with contributions from environmentalists, taxonomists, and social scientists, including artists, who can shape opinions and behavior.

The grafting machine cutting step is the core step of the grafting process. The existing grafting machine cutting mechanism adopts fixed angle cutting and manually adjusts the cutting angle based on experience, and the cutting angle is not definite for rootstock cutting in different growth periods. In this paper, we proposed a method to guide the precise cutting mechanism according to internal and external parameters of melon rootstock at a specific period. First, we constructed a cutting model based on internal and external characteristics of rootstock cutting in the growth period of “two leaves and one core” and clarified the safe cutting area. Second, we designed a rotary precision cutting mechanism for rootstock cutting with automatic angle adjustment and constructed the displacement equation of the cutting trajectory of the cutter according to the cutting model. Last, we examined the cutting effect of the precision cutting mechanism and determined the precise cutting angle of the rootstock cutting mechanism in the growth period. Finally, the cutting effect of the precision cutting mechanism was examined, and the precision cutting angle of the rootstock during the growth period was determined. A comparison test between the precision cutting mechanism and the traditional cutting mechanism was carried out, and visual images of the incision were captured and analyzed. The results show that under the five horizontal cutting angles in the safe cutting area of rootstock, the length of the cut surface is inversely proportional to the cutting angle, and the flatness of the cut surface is directly proportional to the cutting angle. Comprehensive evaluation of the length of the cut surface, the cutting success rate, and the quality of cutting revealed that the average cutting angle of the precision cutting mechanism in the safe cutting area (26°) is better than that of the traditional cutting mechanism. It meets the technical requirements of the cutting technology for mechanically grafted rootstocks. The results provide a reference for studying new rootstock precision cutting mechanisms and cutting angle adaptive control models.

Abstract Glioblastoma (GBM) is a fatal malignancy caused by dysregulation of cellular signal transduction. Internalization plays a key role in maintaining signalling balance. Previous reports showed that Sortilin related VPS10 domain containing receptor 3 (SorCS3) has the ability to regulate internalization. However, the impacts of SorCS3 on the biological processes involved in GBM have not yet been reported. In this study, we investigated the bio-function of SorCS3 in GBM. We found that SorCS3 was significantly downregulated in GBM. In addition, low expression level of SorCS3 predicted poor prognoses in patients with GBM. Here, we proved that SorCS3 suppressed cell invasion and proliferation mainly via NGF/p75NTR pathway in GBM. We found that SorCS3 co-localized with p75NTR in GBM cells and regulated the p75NTR protein level by promoting trafficking of the endosomal to the lysosome. Immunofluorescence (IF) and Co-Immunoprecipitation (Co-IP) detection confirmed that SorCS3 bound to p75NTR, which subsequently increased the internalization of p75NTR, and then transported p75NTR to the lysosome for degradation, ultimately contributing to inhibit of glioma progression. Taken together, our work suggests that SorCS3 is a marker of promising prognosis in GBM patients and suggests that SorCS3 regulates internalization, which plays a pivotal role in inhibiting glioma progression.

Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with feeble immune responses and serious adverse effects still cannot be neglected due to the complicated multifactorial etiology and pathologic microenvironment in tumors. The rapid development of nanomedical science and material science has facilitated the advanced progress of engineering biomaterials to tackle critical issues. The supramolecular biomaterials with flexible and modular structures have exhibited unparalleled advantages of high cargo-loading efficiency, excellent biocompatibility, and diversiform immunomodulatory activity, thereby providing a powerful weapon for cancer immunotherapy. In past decades, supramolecular biomaterials were extensively explored as versatile delivery platforms for immunotherapeutic agents or designed to interact with the key moleculars in immune system in a precise and controllable manner. In this review, we focused on the crucial role of supramolecular biomaterials in the modulation of pivotal steps during tumor immunotherapy, including antigen delivery and presentation, T lymphocyte activation, tumor-associated macrophage elimination and repolarization, and myeloid-derived suppressor cell depletion. Based on extensive research, we explored the current limitations and development prospects of supramolecular biomaterials in cancer immunotherapy.

Gastrointestinal (GI) cancers occur in the alimentary tract and accessory organs. They exert a global burden with high morbidity and mortality. Inside the tumor microenvironment, dendritic cells (DCs) are the most efficient antigen-presenting cells and are necessary for adaptive immune responses such as T and B-cell maturation. However, the subsets of DCs revealed before were mostly based on flow cytometry and bulk sequencing. With the development of single-cell RNA sequencing (scRNA-seq), the tumor and microenvironment heterogeneity of GI cancer has been illustrated. In this review, we summarize the classification and development trajectory of dendritic cells at the single-cell level in GI cancer. Additionally, we focused on the interaction of DCs with T cells and their effect on the response to immunotherapy. Specifically, we focused on the newly identified tumor-infiltrating dendritic cells and discuss their potential function in antitumor immunity.

Background: Diabetic foot ulcer (DFU) is a severe chronic complication of diabetes, that can result in disability or death. Dracorhodin Perchlorate (DP) is effective for treating DFU, but the potential mechanisms need to be investigated. We aimed to explore the mechanisms underlying the acceleration of wound healing in DFU by the topical application of DP through the combination of metabolomics and network pharmacology.Methods: A DFU rat model was established, and the rate of ulcer wound healing was assessed. Different metabolites were found in the skin tissues of each group, and MetaboAnalyst was performed to analyse metabolic pathways. The candidate targets of DP in the treatment of DFU were screened using network pharmacology. Cytoscape was applied to construct an integrated network of metabolomics and network pharmacology. Moreover, the obtained hub targets were validated using molecular docking. After the topical application of DP, blood glucose, the rate of wound healing and pro-inflammatory cytokine levels were assessed.Results: The levels of IL-1, hs-CRP and TNF-α of the Adm group were significantly downregulated. A total of 114 metabolites were identified. These could be important to the therapeutic effects of DP in the treatment of DFU. Based on the network pharmacology, seven hub genes were found, which were partially consistent with the metabolomics results. We focused on four hub targets by further integrated analysis, namely, PAH, GSTM1, DHFR and CAT, and the crucial metabolites and pathways. Molecular docking results demonstrated that DP was well combined with the hub targets.Conclusion: Our research based on metabolomics and network pharmacology demonstrated that DP improves wound healing in DFU through multiple targets and pathways, and it can potentially be used for DFU treatment.

This study was designed to evaluate the optimum additional level of coated complex trace minerals (TMs) and its impacts on the growth performance of broilers through measurement of digestibility of nutrients and intestinal development. In a 56-day trial, a total of 360 one-day-old male yellow-feathered broilers were randomly divided into six dietary treatment groups. Each treatment contained six replicates, with 10 birds. The control group was supplemented with 1,000 mg/kg of uncoated complex TMs in the basal diet (UCCTM1000). The remaining 5 treatments were degressively supplemented with coated complex TMs from 1,000 to 200 mg/kg in the basal diet, which were considered as (CCTM1000), (CCTM800), (CCTM600), (CCTM400), (CCTM200), respectively. Results: On comparing the UCCTM1000 supplementation, the CCTM1000 supplementation decreased the feed to gain ratio (F/G) (P < 0.05), increased digestibility of crude protein (CP) (P < 0.05), crude fat (CF) (P < 0.05), villus height (VH) of duodenum (P < 0.05), and the mRNA expression level of occludin in jejunal mucosa (P < 0.05). In addition, the F/G was lower in the CCTE600 group than that in the CCTE200 group (P < 0.05). The VH to crypt depth (CD) ratio (V/C) of jejunum and ileum in the CCTM400 and CCTM600 groups was higher (P < 0.05) than that in the CCTM1000 group. The serum endotoxin and D-lactate level and CP digestibility were increased by dietary coated complex TMs addition level. The mRNA expression levels of claudin-1 and ZO-1 in the CCTM600 group were higher (P < 0.05) than that in the CCTM1000 group. In conclusion, adding 600 mg/kg of coated complex TMs showed the minimum F/G and the maximum crude protein digestibility and intestine development of yellow-feathered broilers compared with other treatments. This supplementation level of coated complex TMs could totally replace 1,000 mg/kg of uncoated complex TMs to further decrease the dose of TMs and raise economic benefit.

This study was conducted to investigate the effects of yeast culture supplements on the physiological state and growth performance of growing bulls under heat stress conditions and the underlying mechanism. A total of 14 (6.0 ± 1.0 months old) growing bulls with similar body weight were randomly assigned into the control group (YC0g/d) and yeast culture supplement group (YC40g/d). YC0g/d contained three replicates, with two bulls in each replicate, which were fed a basal diet. Meanwhile, the YC40g/d treatment contained four replicates, with two bulls in each replicate, which were fed a basal diet supplemented with 40 g/day of yeast culture per cattle. Growth performance, nutrient digestibility, rumen fermentable metabolites, serum immunity, serum hormones, and serum antioxidant parameters were measured. Results showed that the average daily gain significantly increased (P < 0.05), while the feed-to-gain ratio significantly decreased (P < 0.01) after YC supplementation compared with the YC0g/d. The digestibility of neutral detergent fiber (P < 0.05) was higher in YC40g/d. There were no significant differences in ruminal pH, NH3-N, butyrate, or acetate/propionate (P > 0.05). Besides, the rumen MCP, acetate, propionate, and total VFA content remarkably increased with the supplement of YC (P < 0.05). Yeast culture supplementation increased the concentration of nicotinamide riboside, neuromedin B, peptides, and formyl-5-hydroxykynurenamine. The YC40g/d group had a significantly (P < 0.05) higher serum triiodothyronine level, serum glutathione peroxidase levels, and total antioxidant capacity while having a lower serum malondialdehyde level than the YC0g/d group. In conclusion, the addition of yeast culture in the diet improves the growth performance of growing bulls under heat stress by increasing nutrient digestibility, rumen fermentation function, antioxidant capacity, and rumen metabolites.

Damping-off caused by Pythium aphanidermatum (Pa) is one of the most destructive diseases for watermelon seedlings. Application of biological control agents against Pa has attracted the attention of many researchers for a long time. In this study, the actinomycetous isolate JKTJ-3 with strong and broad-spectrum antifungal activity was screened from 23 bacterial isolates. Based on the morphological, cultural, physiological, and biochemical characteristics as well as the feature of 16S rDNA sequence, isolate JKTJ-3 was identified as Streptomyces murinus. We investigated the biocontrol efficacy of isolate JKTJ-3 and its metabolites. The results revealed that seed and substrate treatments with JKTJ-3 cultures showed a significant inhibitory effect on watermelon damping-off disease. Seed treatment with the JKTJ-3 cultural filtrates (CF) displayed higher control efficacy compared to the fermentation cultures (FC). Treatment of the seeding substrate with the wheat grain cultures (WGC) of JKTJ-3 exhibited better control efficacy than that of the seeding substrate with the JKTJ-3 CF. Moreover, the JKTJ-3 WGC showed the preventive effect on suppression of the disease, and the efficacy increased with increase in the inoculation interval between the WGC and Pa. Production of the antifungal metabolite actinomycin D by isolate JKTJ-3 and cell-wall-degrading enzymes such as β-1,3-glucanase and chitosanase were probably the mechanisms for effective control of watermelon damping-off. It was shown for the first time that S. murinus can produce anti-oomycete substances including chitinase and actinomycin D. This is the first report about S. murinus used as biocontrol agent against watermelon damping-off caused by Pa.

Doubled haploid (DH) technology is an efficient strategy for producing completely homozygous lines for breeding programs. Mutations in the MATRILINEAL (MTL) phospholipase trigger intraspecific haploid induction in cereals. Although an in vivo haploid induction system based on OsMTL-edited plants has been established in rice (Oryza sativa), DH technology is still limited by other factors, such as haploid identification, which is one of the essential steps required for DH technology. In the study, we addressed this technical challenge by integrating specific molecular and phenotypic markers into rice haploid inducers. We first generated large fragment insertion or deletion mutations within the OsMTL gene and designed a pair of primers flanking the mutational sites to be used as the specific and universal molecular markers between wild-type and Osmtl plants. Next, we screened for hairy leaf as a single dominant trait and integrated it into specific molecular marker-based haploid inducers using the cross and self-cross method. When crossing cytoplasmic male sterile lines with these haploid inducers, we utilized the specific InDel marker and hairy leaf phenotypic marker to identify putative haploids (or double haploids). These putative haploids were further confirmed through ploidy and phenotypic analysis, demonstrating the high efficiency of haploid identification using these markers. The haploid induction rate (HIR) of the developed specific molecular and phenotypic marker-based haploid inducers ranged from 3.7% to 12.5%. We have achieved successful integration of distinct molecular and phenotypic markers into rice haploid inducers. Our advanced marker-based system has significantly enhanced the accuracy of haploid identification, thereby expediting the adoption of DH technology in rice breeding.

The rising age of the population in rural China and the labor intensity of grafting have resulted in a decrease in the number of grafters and a subsequent increase in their wages. Manual grafting can no longer satisfy the increasing demand for watermelon-grafted transplanting; thus, machine grafting will be an effective alternative. In order to accelerate the implementation of machine grafting in China, a comparative analysis between the automatic grafting machine (model 2TJGQ-800) and traditional hand grafting was conducted. The reliability and feasibility of machine grafting were evaluated through a comprehensive evaluation of the production capacity and grafting seedling quality. This study focuses on the grafting application of watermelon plug-tray seedlings. The scion and rootstock seeds were sown on 9 November 2022. Grafting experiments using an automatic grafting machine, skilled workers, and ordinary workers were conducted with the root-pruned one-cotyledon grafting method on 24 November 2022. The results showed that the machine grafting had a high uniformity and grafting speed. The grafting speed of the grafting machine was 774 plant·h−1 and 1.65–2.55-fold higher than the hand grafting. With training, workers can improve their grafting speed, but it will still be slower than machine grafting. In addition, there was no significant difference in the grafting survival rate between the machine grafting and hand grafting. However, using machine grafting, the success rate decreased from 100% to 90.07% and the rootstock regrowth rate increased from 18.44% to 72.69%. Incomplete rootstock cutting, clip supply failure, and grafting drop failure are the three main factors that result in machine grafting failure. In conclusion, the grafting machine has advantages in terms of grafting speed and uniformity. Upon improving the accuracy of the cutting mechanism and grafting success rate, it will be adopted by commercial nurseries.

Fannia canicularis (Linnaeus, 1761) is a species from the family Fanniidae. In this study, we sequenced and analyzed the complete mitochondrial genome of F. canicularis for the first time. The circular mitogenome is 15,826 bp in length, and includes 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and a non-coding control region. The family Fanniidae formed a monophyletic clade in the phylogenetic tree based on 13 concatenated PCGs, sister to three other families in Diptera.

Levels of neutralizing antibodies (NAb) after vaccine against coronavirus disease 2019 (COVID-19) can be detected using a variety of methods. A critical challenge is how to apply simple and accurate methods to assess vaccine effect. In a population inoculated with three doses of the inactivated Sinopharm/BBIBP vaccine, we assessed the performance of chemiluminescent immunoassay (CLIA) in its implementation to detect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) specific antibodies, as well as the antibody kinetics of healthcare workers throughout the course of vaccination. The antibody levels of NAb, the receptor-binding-domain (RBD) antibodies and IgG peaked one month after the second and remained at a relatively high level for over three months after the booster injection, while IgM and IgA levels remained consistently low throughout the course of vaccination. The production of high-level neutralizing antibodies is more likely when the inoculation interval between the first two doses is within the range of one to two months, and that between the first and booster dose is within 230 days. CLIA showed excellent consistency and correlation between NAb, RBD, and IgG antibodies with the cytopathic effect (CPE) conventional virus neutralization test (VNT). Receiver operating characteristic (ROC) analysis revealed that the optimal cut-off levels of NAb, RBD and IgG were 61.77 AU/ml, 37.86 AU/ml and 4.64 AU/ml, with sensitivity of 0.833, 0.796 and 0.944, and specificity of 0.768, 0.750 and 0.625, respectively, which can be utilized as reliable indicators of COVID-19 vaccination immunity detection.

Gouty arthritis (GA), as a multifactorial disease, is characterised by intense pain, active inflammation symptoms, and swollen joints. It has utterly complex pathogenesis, of which the amount of research publications on GA has increased during the last few decades. A bibliometric analysis was carried out to investigate the trends, frontiers, and hot spots in global scientific output in GA research over the last decade. We retrieved the Science Citation Index Expanded (SCI-Expanded) of the Web of Science Core Collection (WoSCC) for publications and recorded information published from 2012 to 2021. we carried out the bibliometric analysis and visualisation analysis of the overall distribution of annual outputs, leading countries, active institutions, journals, authors, co-cited references, and keywords with the VOSviewer and CiteSpace. The impact and quality of papers were assessed using a global citation score (GCS). We retrieved 2052 articles and reviews in total. The annual number of publications (Np) related to GA research has increased during the latest decade. China published the most papers, and the USA achieved the highest H-index and number of citations (Nc). The League of European Research Universities (LERU) and Clinical Rheumatology (Clin Rheumatol) are the most productive institutions and periodicals. The total GCS of the paper written by Kottgen, A. in 2013 was 479, ranking the first. The most common keywords were “Gout,” “hyperuricemia,” and “gouty arthritis.” This research revealed that though there was a slight fluctuation in publications related to GA, the Np raised on the whole. China was an enormous creator, and the USA was an influential nation in this domain. The top three contributor authors were Dalbeth, N., Singh, JA., and Choi, HK. There were few investigations on the treatment of GA by Chinese medicine monomer, and the “mechanism,” “pathway”, “nf- kappa-b”, “injury”, “receptor”, and “animal model” were growing research hotspots. Our research illustrated the hotspots of research and development trends in the research field of GA during the last decade. Recognition of the most critical indicators (researchers, countries, institutes, and journals for the release of GA research), hotspots in the research field of GA can be helpful for countries, scholars, and policymakers in this field to understand GA better make decisions.

This study evaluated the effect of glutamate supplementation on the physiological parameters of heat-stressed Hu sheep. Forty-eight male Hu sheep with an average initial body weight of 17.74 ± 0.17 kg were randomly divided into two groups: The control group (CON) was fed a basal diet and a treatment group (GLU) was fed a basal diet + 3 g/head/day of L-glutamate. There were six replications in each group with four sheep in each replication for a 90 days feeding test. Growth performance, serum biochemistry, and serum hormones were measured during phase 1 (1–30 days), phase 2 (31–60 days), and phase 3 (61–90 days) of the experiment; rumen fermentation characteristics, nutrient digestibility, and slaughter performance were measured at the end of the experimental periods. There were no differences in growth performance, serum biochemical indices, and immune indices between CON and GLU during phases 1 and 2. However, a higher average daily gain (ADG), a lower average daily feed intake (ADFI), and a lower F:G ratio (ADFI/ADG) were observed in GLU during phase 3 (p < 0.05). Serum levels of glutamate, globulin, immunoglobulin A, immunoglobulin G, immunoglobulin M, and growth hormone in GLU were higher than those in CON only on day 90 (p < 0.05). Serum levels of heat shock protein 70, adrenocorticotrophic hormone, corticosterone, triiodothyronine, and tetraiodothyronine in GLU were lower than those in CON on day 90 (p < 0.05). At the end of the experiment, ruminal pH, microbial crude protein, ammonia nitrogen, and isovalerate concentrations in GLU were higher than those in CON (p < 0.05). The apparent digestibility of dry matter, organic matter, and crude protein in GLU was higher than those in CON (p < 0.05). There were no differences in carcass traits and organ indices but spleen weight and spleen index tended to be higher in GLU. In conclusion, dietary glutamate supplementation improved rumen fermentation, increased nutrition digestibility and metabolism, enhanced immunity, and promoted growth performance of heat-stressed Hu sheep. This suggests that a longer period of glutamate supplementation (not less than 60 days) at a level of 3 g/head/day is beneficial to Hu sheep under heat stress.

Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus-neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients’ antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigen-specific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.

The labor-efficient automation of grafting has been recognized as a key factor in the wider adoption of grafting. In growing cucurbits, the root pruned one-cotyledon grafting method is the most commonly used method with grafting machines. The cutting angle, which affects the matching of the rootstock and scion, is key to the survival of the graft seedling. In the production of cucurbit graft seedlings, the cutting parameters are established based on experience, leading to low grafting success. To determine accurate cutting parameters, the watermelon cv. ‘Zaojia84-24′ was used as the scion and the pumpkin cv. ‘Zhenzhuang’ was used as rootstock, and two one-way experiments investigating the cutting angle of the watermelon scion and the rootstock as factors were conducted. The cutting angle of the rootstock and scion had no significant effect on the xylem reconnection rate or the grafting survival rate. A larger cutting angle for the rootstock and scion led to a delay in the reconnection of the phloem. Different cutting angles for the scion significantly affected the growth of the scion after grafting. Compared with a scion graft cutting angle of 10° (SL), graft cutting angles of 14° (SM) and 20° (SS) led to significantly greater scion dry weights, with increases of 16.00% and 18.61%, respectively. Different cutting angles of the rootstock significantly affected the growth of roots after grafting. Compared with a rootstock graft cutting angle of 10° (RL), graft cutting angles of 17° (RM) and 27° (RS) led to significantly greater root dry weights, with increases of 29.33% and 22.54%, respectively. The results of this study can provide a reference for the design of cutting mechanisms for cucurbit grafting robots, improving the cutting precision of grafting robots.

Based on Bohr’s model of hydrogen atom, the main purpose of this paper is to propose a new hypothesis for the model of hydrogen atom and perform mathematical calculations and verifications using experimental values and physical constants. The new model can not only provide the explanations that the existing theories failed to provide, but also can be used to construct neutrons, atomic nuclei, and individual atoms and molecules by involving only electrons and protons and their interactions. This means we only need to know how single electron and proton interact with each other, then we can establish a full model of hydrogen atom, and then we can establish other atomic nuclei. After all, all matter in the universe is made from hydrogen atoms through nuclear fusion.

Objective. Remote ischemic conditioning (RIC) is a cardioprotective method in ischemia/reperfusion (I/R) injury. This study investigated the mechanism of Rho-kinase-mediated autophagy in RIC. Methods. Sixty male Sprague–Dawley rats were randomly divided into six groups: sham, I/R, RIC, I/R+fasudil, RIC+wortmannin, and RIC+fasudil+wortmannin. Throughout the experiment, mean arterial pressure and heart rate were continuously monitored. Histopathology and ultrastructure and myocardial enzymes’ expression were evaluated to determine the degree of cardiac injury. The protein expression of the Rho-kinase substrates myosin light chain (MLC) and myosin phosphatase target subunit 1 (MYPT1), autophagy-related protein light chain 3-II (LC3-II) and Beclin 1, and protein kinase B (AKT) was measured in the myocardial tissue. Results. Compared with the sham group, the mean arterial pressure and heart rate were decreased, myocardial enzyme levels were increased, and myocardial damage was aggravated in the I/R group; however, RIC improved these alterations. The expression of phosphorylated MLC and MYPT1 was lower, while LC3-II, Beclin 1, and phospho-AKT expression levels were higher in the RIC group compared with the I/R group. Obviously, treatment of the I/R group rats with fasudil, a Rho-kinase inhibitor, significantly ameliorated the I/R effects, whereas treatment of the RIC group rats with wortmannin, a phosphatidylinositol-3 kinase (PI3K) inhibitor, inhibited the RIC protective effects. Moreover, the rats in the RIC+fasudil+wortmannin group showed similar changes to those in the RIC+wortmannin group. Conclusion. These results showed that RIC protected the myocardium from I/R injury by suppressing Rho-kinase and the underlying mechanism may be related to enhancing autophagy via the PI3K/AKT pathway.

Objectives. Diabetic foot ulcer (DFU) is one of the devastating complications of diabetes. It has high mortality and disability rates. The number of research articles on DFUs has increased. This study was designed to explore the global trends and research hotspots of DFUs to benefit researchers in shaping future research directions. Methods. Literatures relating to DFU from 2004 to 2020 were retrieved from the Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). The current status of DFU research (including publications, journals, the performances of relevant countries, institutions, and authors and the research trends and hotspots of DFU) was analyzed with the WoSCC. VOSviewer v1.6.10.0 was utilised for cocitation, coauthorship, cooccurrence analyses, and bibliographic coupling. Results. A total of 5869 publications on DFUs were retrieved. We performed a longitudinal review of publications over 17 years: 4500 articles and 865 review articles on DFUs published from 2004 to 2020 were analyzed. The total citation was 107,296. The USA (n=1866), England (n=606), and China (n=599) were the three largest contributors. The University of Washington had the greatest number of publications within this time period (n=103), and it had the most cooperative units and was in the core position in all research institutions, followed by the University of Manchester (n=94) and the University of Miami (n=92). Armstrong DG (91/1.69%) and Lavery LA (55/1.19%) should be regarded as scholars who have made outstanding contributions. The top journal with the greatest total link strength was Diabetes Care. Analysis showed that the global research hotspots of DFU focused on lower limb amputation, diabetic foot infection, and treatment and management of DFU. Studies on osteomyelitis, wound therapy and management, multidisciplinary integration and mechanism of DFUs, and its related diseases are the research fronts that should be closely watched in the future. Conclusions. This study revealed the current research status and hotspots in the domain of DFU over the past 17 years, which can help researchers to further pinpoint potential perspectives on hot topics and research frontiers.

Recently, the identification of several circular RNAs (circRNAs) as vital regulators of microRNAs (miRNAs) underlines the increasing complexity of non-coding RNA (ncRNA)-mediated regulatory networks. This study aimed to explore the effects of mmu_circ_0000790 on the biological behaviors of pulmonary artery smooth muscle cells (PASMCs) in hypoxic pulmonary hypertension (HPH). The HPH mouse model and hypoxia-induced PASMC model were initially established, and the expression of mmu_circ_0000790 in the pulmonary vascular tissues and hypoxic PASMCs was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). A series of in vitro experiments such as dual-luciferase, RNA pull-down, and RNA-binding protein immunoprecipitation (RIP) assays were conducted to evaluate the interactions among mmu_circ_0000790, microRNA-374c (miR-374c), and forkhead transcription factor 1 (FOXC1). The potential physiological functions of mmu_circ_0000790, miR-374c, and FOXC1 in hypoxic PASMCs were investigated through gain- and loss-of function approaches. Upregulated mmu_circ_0000790 was found in both the HPH-pulmonary vascular tissues and hypoxic PASMCs. Additionally, mmu_circ_0000790 could competitively bind to miR-374c and consequently upregulate the target gene of miR-374c, FOXC1. It was also observed that mmu_circ_0000790 induced proliferation and inhibited apoptosis of hypoxic PASMCs, which further promoted the pulmonary vascular remodeling in mice with HPH. Therefore, we speculate that mmu_circ_0000790 may serve as a prospective target for the treatment of patients with HPH.

Abstract. Background:. China's two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes. This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes in China. Methods:. This secondary analysis of a multicenter retrospective cohort study included data of childbearing women from 39 hospitals collected in urban China during 2011 to 2012. Logistic regression was used to assess the adjusted odds ratios (aOR) of adverse outcomes in different age groups in comparison to women aged 20 to 24 years. The adjustments included the location of the hospital, educational level, and residence status. Clinically cutoff age was defined as the age above which the aOR continuously become both statistically (P 2) significant. Results:. Overall, 108,059 women were recruited. In primiparae, clinically cutoff maternal ages for gestational diabetes (aOR: 2.136, 95% confidence interval [CI]: 1.856–2.458, P

Objective: Ultrasound determination of chorionicity is poor in early pregnancy in China. In an effort to increase the accuracy rate of prompt chorionicity determination, clinical training was provided to primary care physicians. This study assesses the effects of implementing clinical guidelines on chorionicity determination. Methods: A multi-centered cohort study was conducted between January 2014 and June 2017 in 12 hospitals without fetal medicine centers. In 2014, the obstetricians and ultrasound physicians were trained in clinical practice and ultrasound examination relating to chorionicity determination. Linear and binary regression analyses were conducted to identify the effects of introducing the new protocols, including the diagnosis rate of chorionicty and perinatal outcomes, taking the data from 2014 as a baseline. Pregnancy outcomes were additionally adjusted for maternal age. Results: During the period of this study, 3,599 twin pregnancies from 12 centers were enrolled, and a total of 2,998 twin pregnancies were extracted. The rate of overall chorionicity determination, including antenatal and postpartum diagnosis, increased successively from 49.5% in 2014 to 93.5% in 2017 (P < 0.0001). The rate of ultrasonic chorionicity diagnosis before 14 weeks increased from 25.2% in 2014 to 65.0% in 2017 (P < 0.0001). These changes were associated with decreasing incidence of preterm birth, a lower risk of stillbirth, whether for one (P = 0.0456 in 2016) or two fetuses (P = 0.0470 in 2016; P = 0.0042 in 2017) and a decreased rate of admission to neonatal intensive care unit (43.0% in 2014, 37.4% in 2017; P = 0.0032). Conclusions: The implementation of a clinical practice guideline improved both overall and early chorionicity determinations. Regular training workshops of antenatal care are recommended to further promote capability in clinical diagnosis and treatment.

Diopside, an important component of the crustal and upper mantle, plays an important role in the formation of nephrite. Polysynthetic twinning in natural diopside, especially from skarns, has rarely been systematically researched. Here, the polysynthetic twinning of natural diopside was investigated in two skarn-type nephrite deposits (Niewang and Tatliksu) in Qiemo, Xinjiang, China. Petrographic observations revealed periodic alternations of dark–light lamellae under cross-polarized light and parallel striations under plane-polarized light, whereas backscattered electron images indicated high homogeneity, which suggested a type of mechanical polysynthetic twinning. According to the optical indicatrix, twins were predominantly oriented as a (100)[100] system. Raman spectra and chemical data show that pyroxenes in nephrite are close to the Di end-member with 0.90–1.04 a.p.f.u. Mg and 0.98–1.05 a.p.f.u. Ca. Both diopside and tremolite from Tatliksu contain slightly higher Fe than those from Niewang. Given the seismic origin of mechanical clinopyroxenes twins, twins of studied diopsides are likely to be attributed to Paleozoic-Mesozoic paleoearthquakes in the Altyn Mountain. A shear stress ≥ 140 MPa and a differential stress greater than 280 MPa are suggested as conditions linked to generation of the twinning of diopsides in the nephrite deposits. The replacement of diopside by tremolite along its twin planes highlights the potential gemological implications, as such replacement by tremolite probably facilitated the formation of dense, fine fibre textures in the nephrites.

Quasi-two-dimensional (quasi-2D) friction models have been widely investigated in transient pipe flows. In the case of viscoelastic pipes, however, the effect of different values of the Reynolds number (Re) on pressure fluctuations (which can lead to water hammer) have not been considered in detail. This study establishes a quasi-2D friction model employing an integral total energy method and investigates the work due to frictional and viscoelastic terms at different Re values. The results show that viscoelastic work (WP) and frictional work (Df) increase with an increase in Re. However, when the initial Re values are high, the Df values are much larger than the WP values. In addition, for Re < 3 × 105, the 1D model underestimated the viscoelastic terms. There was no significant difference between the two models for Re > 3 × 105. In the case of different initial Re values, the two models produced almost the same values for WP. This study provides a theoretical basis for investigating transient flow from the perspective of energy analysis.

An experiment was conducted to determine the effects of supplementing the diet of Jinjiang bulls with guanidinoacetic acid (GAA) on their feed efficiency [feed efficiency were evaluated with feedlot average daily gain (ADG), average daily feed intake (ADFI), and feed-to-gain ratio (F:G)], blood measures, and meat quality. Forty-five Jinjiang bulls (24 ± 3 months old and 350.15 ± 30.39 kg by weight) were randomly distributed among five experimental groups (each n = 9) and each group was randomly fed with one of five diets (concentrate: roughage ratio of 60:40): (1) control; (2) 0.05% GAA; (3) 0.1% GAA; (4) 0.2% GAA; and (5) 0.4% GAA, respectively. After a 52-days feeding trial, five bulls from the control group and five bulls from the optimal GAA supplementing group were randomly selected and slaughtered for collection of the longissimus thoracis (LT) and semitendinosus (SM) muscles to determine meat quality. The results showed that dietary GAA improved the ADG, decreased the value of F:G, and affected blood measures and antioxidant variables. Supplementing 0.2% GAA into the diet was optimal for feeding efficiency and most of the measured blood measures. Supplementing 0.2% GAA into the diet increased the a* (redness) values, and b* (yellowness) values, and the amount of creatine kinase (CK), muscle glycogen, creatinine (CRE), and laminin (LN) in LT muscles. However, it decreased the drip loss, L* (lightness) value, and lactate dehydrogenase (LDH) content of LT muscles. Drip loss and shear force decreased in SM muscles, as did the amount of type IV collagen (CV–IV). In conclusion, supplementing 0.2% GAA into the diet could enhance feed efficiency to improve beef growth and meat quality.

Water temperature affects the peak pressure damping of transient flows in viscoelastic pipes. Owing to the viscoelastic properties of pipes, the accuracy of peak pressure damping simulations hinges on both viscoelastic and frictional factors. In simulations, the influence of both factors on peak pressure damping at different water temperatures is unclear. In this study, the Kelvin–Voigt model with both a quasi-steady friction model and modified Brunone model was employed. Based on experimental data, the accuracy of simulated peak pressure damping was verified at four different water temperatures (13.8, 25, 31, and 38.5 °C). From the perspective of energy transfer and dissipation, the influence of viscoelastic and frictional factors on peak pressure damping were clarified, and the applicability of different friction models was determined based on the contributions of viscoelastic and frictional factors to peak pressure damping. The numerical results indicate that the viscoelastic properties of pipes have a greater impact on peak pressure damping than their frictional properties at 25, 31, and 38.5 °C. Higher temperatures result in a delay in the rate of work and a decrease in the frequency of work performed by viscoelastic pipes. Viscoelastic properties play a more important role than frictional ones in calculating peak pressure damping as the water temperature increases. In addition, the one-dimensional quasi-steady friction model can accurately simulate peak pressure damping within a specified water temperature range.

Sorghum-sudangrass hybrid silage has poor fermentation characteristics owing to a high moisture content. Accordingly, a 3 × 4+1 factorial design was applied to investigate the effects of adding different types and amounts of hay (corn stalk, wheat straw, and alfalfa hay at 12.5 kg t-1, 25 kg t-1, 37.5 kg t-1, and 50 kg t-1) on the nutritive value, fermentation quality, 72 h dry matter digestibility, and gas dynamics in vitro to simulate the rumen fermentation of sorghum-sudangrass hybrid silage. Separated silage of sorghum-sudangrass hybrids had a high butyric acid content and a FLIEG’s scores evaluation ranking of only “Fair.” The addition of hay significantly improved the fermentation quality of mixed silage. With respect to hay type, adding wheat straw had the best fermentation quality, alfalfa hay had the best nutritive value, in vitro dry matter digestibility (IVDMD) (662.41 g kg-1), constant fractional rate (C) (0.28 mL h-1), and the average gas production rate (AGPR) (32.70 mL h-1) content. There were no differences in the cumulative gas production at 72 h (GP72h), asymptotic gas production generated at a constant fractional rate (A), and lag time before gas production commenced (lag) among the three hay types. With respect to quantity, 25 kg t-1 hay had the best fermentation quality, 50 kg t-1 hay had the best nutritive value and highest IVDMD content (662.81 g kg-1), 37.5 kg t-1 hay had the highest C (0.28 mL h-1) and AGPR (31.48 mL h-1) contents, 25 kg t-1 hay had the highest Half time (2.20 h), and there were no significant differences in GP72h, A, and lag among the four amounts. Considering both nutritive value and fermentation quality, the best mixed silage mode was 37.5 kg t-1 wheat straw.

An experiment was conducted to determine the effects of adding different amounts of daidzein in diet on the fermentation parameters and bacterial community composition in the rumen of finishing cattle. A total of thirty head of 2-year-old finishing Xianan cattle were divided by weight into three groups and randomly allotted by group to one of three dietary treatments: (1) control; (2) 500 mg/kg daidzein and (3) 1000 mg/kg daidzein. All cattle were slaughtered to obtain rumen samples after a 80-d feeding trial. Results showed that adding 500 mg/kg daidzein reduced the operational taxonomic units (OTU) numbers, Shannon index and Chao1 index compared with control and 1000 mg/kg daidzein groups. Compared with control group at phylum level, Planctomycetos and Tenericutes were significantly more abundant in 500 mg/kg daidzein group, Verrucomicrobia and Fusobacteria were significantly rarer in 1000 mg/kg daidzein group. Compared with control group at genus level, Prevotella and Ruminococcus were significantly more abundant in 500 mg/kg daidzein group, Prevotella was significantly more abundant and Dethiosulfatibacter was significantly rarer in 1000 mg/kg daidzein group. Adding 1000 mg/kg daidzein significantly improved the total volatile fatty acids (TVFA) concentration and acetate content and significantly reduced the butyrate content compared with control group. Daidzein changed the fermentation parameters mainly by impacting the abundance of Prevotella and Ruminococcus. Current results suggest that adding 1000 mg/kg daidzein in diets can improve the rumen fermentation function for finishing Xianan cattle.

Uridine diphosphate glucose pyrophosphorylase (UDP-glucose pyrophosphorylase, UGPase), as one of the key enzymes in polysaccharide synthesis, plays important roles in the growth and development of plants. In this study, the DoUGP gene of Dendrobium officinale was overexpressed. The expression of DoUGP and genes playing roles in the same and other saccharide synthesis pathways was determined, and the total soluble polysaccharide was also tested in wild-type and transgenic seedlings. We also performed freezing and osmotic stress treatments to determine whether overexpression of DoUGP could influence stress resistance in transgenic seedlings. Results showed that mRNA expression levels of DoUGP and its metabolic upstream and downstream genes in the transgenic seedlings were increased compared to the expression of these genes in wild-type seedlings. Additionally, most CSLA genes involved in the biosynthesis of mannan polysaccharides were significantly upregulated. The total polysaccharide and mannose content of transgenic seedlings were increased compared to the content of wild type, and enhanced stress tolerance was found in the overexpressed seedlings compared to the wild type.