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Abstract Apoptosis is a genetically programmed form of cell death that is substantially conserved across the evolutionary tree. Apoptotic cell elimination includes recognition, phagocytosis, and degradation. Failure to clear apoptotic cells can ultimately cause a series of human diseases, such as systemic lupus erythematosus, Alzheimer's disease, atherosclerosis, and cancer. Consequently, the timely and effective removal of apoptotic cells is crucial to maintaining the body's homeostasis. GPCRs belong to the largest membrane receptor family. Its intracellular domain exerts an effect on the trimer G protein. By combining with a variety of ligands, the extracellular domain of G protein initiates the dissociation of G protein trimers and progressively transmits signals downstream. Presently, numerous G protein‐coupled receptors (GPCRs) have been identified as participants in the apoptosis signal transduction pathway and the apoptotic cell clearance pathway. Therefore, studies on the mechanism of GPCRs in the clearance of apoptotic cells is important for the development of GPCRs therapeutics.

Some rock joints exhibit significant brittleness, characterized by a sharp decrease in shear stress upon reaching the peak strength. However, existing models often fail to accurately represent this behavior and are encumbered by numerous parameters lacking clear mechanical significance. This study presents a new statistical damage constitutive model rooted in both damage mechanics and statistics, containing only three model parameters. The proposed model encompasses all stages of joint shearing, including the compaction stage, linear stage, plastic yielding stage, drop stage, strain softening stage, and residual strength stage. To derive the analytical expression of the constitutive model, three boundary conditions are introduced. Experimental data from both natural and artificial rock joints is utilized to validate the model, resulting in average absolute relative errors ranging from 3% to 8%. Moreover, a comparative analysis with established models illustrates that the proposed model captures stress drop and post-peak strain softening more effectively, with model parameters possessing clearer mechanical interpretations. Furthermore, parameter analysis is conducted to investigate the impacts of model parameters on the curves and unveil the relationship between these parameters and the mechanical properties of rock joints. Importantly, the proposed model is straightforward in form, and all model parameters can be obtained from direct shear tests, thus facilitating the utilization in numerical simulations.

Abstract Background A few previous cross-sectional studies investigated correlated factors of suicidal ideation or suicide attempts among suicide prevention hotline callers; however, scarcely any evidence was from a longitudinal study. In addition, it is still unclear whether improvements in some suicide risk factors could reduce the occurrence of subsequent suicidal acts. This longitudinal study focusing on the risk factors for subsequent suicidal acts among adolescent and young adult callers with high suicide risk aims to fill this gap. Methods This study recruited 12–25-year-old high-risk callers to a China nationwide suicide prevention hotline. Potential risk factors, including hopefulness, psychological distress, depression, history of suicide attempts, alcohol or substance misuse, and acute life events, were examined during the index calls, and improvements in hopefulness, psychological distress, and suicide intent were assessed before ending the index calls. The recruited callers were followed up 12 months after their index calls. The primary outcome was the occurrence of suicidal acts (suicide attempts or suicide death) during follow-up. Kaplan–Meier survival curves, log-rank tests, and Cox proportional hazards model were used. Results During the follow-up period, 271 of 1656 high-risk adolescent and young adult callers attempted suicide, and seven callers died by suicide. After adjusting for demographic variables, low hopefulness (Hazard Ratio [HR] = 2.03, 95% Confidence Interval [CI]=[1.47, 2.80]) at the beginning of the index call was associated with a higher risk for subsequent suicidal acts, whereas improvements in psychological distress (HR = 0.61, 95%CI [0.41, 0.89]) and suicidal intent (HR = 0.56, 95%CI [0.38, 0.84]) during the index call reduced the risk of subsequent suicidal acts. In addition, alcohol or substance misuse (Model 2, HR = 1.65, 95%CI [1.11, 2.46]) and suicide attempt history(Model 1: one episode, HR = 1.96, 95%CI=[1.05, 3.66]; two or more episodes, HR = 2.81, 95%CI [1.59, 4.96]. Model 2: one episode, HR = 2.26, 95%CI [1.06, 4.82]; two or more episodes: HR = 3.28, 95%CI [1.63, 6.60]) were risk factors for subsequent suicidal acts. Conclusions While suicide prevention hotline operators deliver brief psychological interventions to high-risk adolescent and young adult callers, priority should be given to callers with low hopefulness and to the alleviation of callers’ high psychological distress and suicide intent.

ABSTRACT: Coccidiosis, which is caused by Eimeria species, results in huge economic losses to the poultry industry. Arbor Acres (AA) broilers and yellow-feathered broilers are the dominant broilers in northern and southern China, respectively. However, their susceptibility to coccidiosis has not been fully compared. In this study, the susceptibility of yellow-feathered broilers, AA broilers and Lohmann pink layers to E. tenella was evaluated based on mortality rate, relative body weight gain rate, intestinal lesion score, oocyst output, anticoccidial index (ACI), and cecum weight and length. The yellow-feathered broilers were shown to produce significantly fewer oocysts with higher intestinal lesion score compared to AA broilers, which had the highest growth rates and ACI scores. Subsequently, changes in the cecal microbiota of the 3 chicken lines before and after high-dose infection (1 × 104 oocysts) with E. tenella were determined by 16S rRNA sequencing. The results showed that composition of the microbiota changed dramatically after infection. The abundance of Firmicutes and Bacteroidetes in the infected chickens decreased, and Proteobacteria increased significantly among the different chicken lines. At the genus level, Escherichia increased significantly in all 3 groups of infected chickens, but Lactobacillus decreased to 0% in the infected yellow-feathered broilers. The results of the study indicate that the susceptibility to E. tenella varies among the 3 chicken lines, and that changes in intestinal microbiota by E. tenella-infection among the different chicken lines had a similar trend, but to different degrees. This study provides basic knowledge of the susceptibility in the 3 chicken lines, which can be helpful for the control and prevention of coccidiosis.

ObjectivesTo avoid the oncologic risks of ipsilateral regional flaps, this study aimed to explore the feasibility and clinical outcomes of the contralateral-based facial artery myomucosal island flap (C-FAMMIF) for oral T2–T3 oncologic defects reconstruction.MethodsA study of flap anatomy was conducted on 7 cadaver samples and a cohort of 24 patients who received C-FAMMIF reconstruction after malignancy resection were retrospectively researched. A balanced anterolateral thigh flap (ALT) group of 47 patients was extracted as control group using propensity score matching method. Progression-free survival (PFS), functional outcomes, and donor site complications were assessed.ResultsConsistent blood supply and drainage through facial artery and vein with median maximum pedicle length of 106 mm supported contralateral reconstruction. The superficial vein drainage pattern indicated safer flap harvest at contralateral neck under circumstances of ipsilateral neck dissections. The pedicle and marginal facial nerve formed three anatomical patterns. The surgical management of each was described. Patients with ipsilateral pN+ neck accounted for 41.7% and 40.4% in the C-FAMMIF and ALT group, respectively. The 2-year PFS rate between the C-FAMMIF and ALT groups was not significantly different (88.2% in C-FAMMIF group and 84.6% in ALT group, respectively, p = 0.6358). Promising recoveries were observed for swallowing function and tactile sensation. The donor sites healed upon primary closure without trismus or permanent facial palsy.ConclusionOur findings suggested that C-FAMMIF is feasible and safe for T2-T3 oral oncologic defect reconstruction in patients with ipsilateral cN+ neck.

Abstract Background The ageing of the population has become an escalating problem in China, which has led to an increasing demand for healthcare throughout society. The care services of elderly institutions, as a more mature way of aging, can alleviate various social problems brought about by ageing to a certain extent. The aim of this paper is to explore the degree of acceptance of institutional care by rural elderly people in Shandong Province and the factors that influence whether rural elderly people accept institutional care services. Methodology Based on the theory of planned behavior, an analytical framework was constructed for the willingness of rural elderly people to receive nursing services from elderly care institutions. Using survey data from 192 rural elderly people in Shandong Province, descriptive statistics, binary logistic regression, and horizontal comparative analysis methods were used to analyze the willingness of rural elderly people to provide for the elderly and its influencing factors. Result Only 17.71% of respondents expressed willingness to receive services from elderly care institutions. Among them, education level, trust in elderly care institutions, and support from adult children have a significant positive impact on whether rural elderly people receive nursing services from elderly care institutions; The number of children, the level of understanding of elderly care institutions, neighbors' choices of elderly care methods, and their ability to contribute to the family have a significant negative impact on whether rural elderly people receive nursing services from elderly care institutions. There are significant differences in the willingness and influencing factors of rural elderly people to provide for the elderly among different regions. Conclusion The non-acceptance of institutional care by rural older people is a general phenomenon rather than a sample characteristic, thus justifying the supplementary status of institutional care services. The pension intention of the rural elderly in Shandong Province is obviously affected by personal will factors, and the influencing factors are various. The traditional concept of old-age care in Shandong province has a strong path-dependent effect on the choice of the rural elderly. There is heterogeneity in the willingness and influencing factors of the rural elderly in different regions and countries. Based on this, this paper puts forward the following suggestions: strengthen the spiritual and cultural construction of residents; The government should pay attention to the correct guidance of public opinion; And increase pension subsidies. It is hoped that reduce the burden of national elderly care through these suggestions.

Laser powder bed fusion (LPBF) is one of the high-precision additive manufacturing techniques for producing complex 3D components. It is well known that defects appear in additive-manufactured parts, and they deeply affect the fatigue properties; even heat treatment is performed after printing. In order to meet the safe-life design requirements of additive-manufactured aircraft structures, the effects of build direction and heat treatment on defects and fatigue properties need to be quantified. Hence, Ti6Al4V alloy samples with different build directions were designed and printed by LPBF. X-ray computed tomography was used to quantitatively analyze the defect size, the sphericity, and the defect orientation. And their effects on fatigue properties were studied. An extended effective defect size and a defect-based fatigue anisotropy evaluation process are proposed to qualify the effects of the defect size, sphericity, and defect orientation. It is shown that the build direction can affect the porosity distribution and maximum defect size, while the annealing treatment can cause the coalescence of small defects and higher porosity. The defect orientation exhibited a fluctuating trend of 0°–90°–0°–90°–0° as the volume increased. The elongated lack of fusion defects related to the build direction was the main crack source and could lead to fatigue anisotropy of LPBF Ti6Al4V.

The objective of this study was to evaluate the effects of pre-exercise L-citrulline supplementation on the athletic performance of Yili speed-racing horses during a high-intensity exercise. On the 20th day of the experiment, blood samples were collected at 3 h and 6 h post-supplementation to measure the amino acid and polyamine concentrations. On the 38th day of the experiment, the horses participated in a 2000 m speed race, and three distinct blood samples were gathered for assessing blood gases, hematological parameters, the plasma biochemistry, antioxidant parameters, and NO concentrations. The results indicate that the L-citrulline group showed a significant increase in the plasma citrulline and arginine concentrations. Conversely, the concentrations of alanine, serine, and threonine were significantly decreased. The glycine concentration decreased significantly, while there was a trend towards an increase in the glutamine concentration. Additionally, the levels of putrescine and spermidine in the plasma of the L-citrulline group were significantly increased. In terms of exercise performance, L-citrulline can improve the exercise performance of sport horses, significantly reduce the immediate post-race lactate levels in Yili horses, and accelerate the recovery of blood gas levels after an exercise. Furthermore, in the L-citrulline group of Yili horses, The levels of the total protein of plasma, superoxide dismutase, catalase, and lactate dehydrogenase were significantly increased both 2 h before and 2 h after the race. The total antioxidant capacity showed a highly significant increase, while the malondialdehyde content significantly decreased. In the immediate post-race period, the creatinine content in the L-citrulline group significantly increased. In conclusion, this study demonstrates that L-citrulline supplementation can influence the circulating concentrations of L-citrulline and arginine in Yili horses, enhance the antioxidant capacity, reduce lactate levels, and improve physiological and biochemical blood parameters, thereby having a beneficial effect on the exercise performance of athletic horses.

Abstract The impact of Tim-3 (T cell immunoglobulin and mucin domain-containing protein 3) on cisplatin-induced acute kidney injury was investigated in this study. Cisplatin-induced Tim-3 expression in mice kidney tissues and proximal tubule-derived BUMPT cells in a time-dependent manner. Compared with wild-type mice, Tim-3 knockout mice have higher levels of serum creatinine and urea nitrogen, enhanced TUNEL staining signals, more severe 8-OHdG (8-hydroxy-2’ -deoxyguanosine) accumulation, and increased cleavage of caspase 3. The purified soluble Tim-3 (sTim-3) protein was used to intervene in cisplatin-stimulated BUMPT cells by competitively binding to the Tim-3 ligand. sTim-3 obviously increased the cisplatin-induced cell apoptosis. Under cisplatin treatment conditions, Tim-3 knockout or sTim-3 promoted the expression of TNF-α (tumor necrosis factor-alpha) and IL-1β (Interleukin-1 beta) and inhibited the expression of IL-10 (interleukin-10). NF-κB (nuclear factor kappa light chain enhancer of activated B cells) P65 inhibitor PDTC or TPCA1 lowed the increased levels of creatinine and BUN (blood urea nitrogen) in cisplatin-treated Tim-3 knockout mice serum and the increased cleavage of caspase 3 in sTim-3 and cisplatin-treated BUMPT cells. Moreover, sTim-3 enhanced mitochondrial oxidative stress in cisplatin-induced BUMPT cells, which can be mitigated by PDTC. These data indicate that Tim-3 may protect against renal injury by inhibiting NF-κB-mediated inflammation and oxidative stress.

Silicon fertilisers are widely utilised to achieve higher productivity in global terrestrial ecosystems, but their impact on the carbon cycle remains unclear. In this study, we used a meta-analysis approach to quantify the response of carbon pools and fluxes in terrestrial ecosystems worldwide to the application of silicon fertiliser while also investigating the factors influencing this response. The findings indicated that silicon fertiliser application led to significant increases in various carbon components: plant aboveground carbon increased by 22.9%, plant belowground carbon increased by 17.3%, litter carbon increased by 8.3%, and the SOC content increased by 8.6%. Furthermore, the net photosynthetic rate of plants was significantly enhanced by 28.1% through the application of silicon fertiliser, along with a notable increase of 36.9% in the net primary productivity of ecosystems, which exhibited a strong correlation with alterations in ecosystem carbon pools. A considerable reduction of 29.6% in soil CH4 emissions was observed, whereas the influence of silicon fertiliser on the litter decomposition rate and net soil CO2 emissions was not statistically significant. Moreover, fertilisation (such as vegetation and soil types), climatic conditions, and silicon fertiliser application techniques have been found to affect the responses of carbon pools and fluxes to silicon fertiliser application. Finally, a potential mechanism by which silicon fertilisation can affect plant growth, litterfall, soil organic carbon stability, and soil carbon emissions directly and indirectly by changing the available silicon and soil pH is proposed to explain the positive effects of silicon fertiliser application on terrestrial ecosystem carbon pools. This effect may change owing to the influence of fertilisation technology, fertilisation, climate, and other factors.

ABSTRACT: Avian coccidiosis caused by Eimeria is a serious parasitic disease that poses a threat to the poultry industry. Currently, prevention and treatment mainly rely on the administration of anticoccidials and live oocyst vaccines. However, the prevalence of drug resistance and the inherent limitations of live vaccines have driven the development of novel vaccines. In this study, the surface protein (Et-SAG14), a previously annotated rhoptry protein (Eten5-B), and a gametocyte phosphoglucomutase (Et-PGM1) were characterized and the vaccine potential of the recombinant proteins were evaluated. Et-SAG14 was dispersed in the form of particles in the sporozoite and merozoite stages, whereas Et-PGM1 was distributed in the apical part of the sporozoite and merozoite stages. The previously annotated rhoptry Eten5-B was found not to be located in the rhoptry but distributed in the cytoplasm of sporozoites and merozoites. Immunization with rEten5-B significantly elevated host interferon gamma (IFN-γ) and interleukin 10 (IL-10) transcript levels and exhibited moderate anticoccidial effects with an anticoccidial index (ACI) of 161. Unexpectedly, both recombinant Et-SAG14 and Et-PGM1 immunization significantly reduced host IFN-γ and IL-10 transcription levels, and did not show protection against E. tenella challenge (ACI < 80). These results suggest that the rEten5-B protein can trigger immune protection against E. tenella and may be a potential and effective subunit vaccine for the control of coccidiosis in poultry.

Penis et testis cervi is one of the precious traditional Chinese medicines (TCMs) in China, which, when authentic, is sourced from species of Cervi nippon Temmink (C. Nippon) and Cervi elaphus Linnaeus (C. elaphus L). Authentication of species of Penis et testis cervi remains technically challenging. This study attempted to modify the species-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) method using restriction enzyme Hpy188III for the identification of Penis et testis cervi species. First, the cytochrome b (Cyt b) and cytochrome c oxidase subunit I (COI) genes in mitochondrial DNA from two authentic species and their counterfeits or adulterants were downloaded and analyzed with bioinformatics tools to establish the phylogenetic tree, then a series of primers were designed, and the restriction enzyme sites were confirmed. Genomic DNA was extracted from all samples by the improved SDS method. Species-specific PCR reactions were optimized to differentiate authentic Sika deer and Red deer Penis et testis cervi from their counterfeits or adulterants. PCR-RFLP using single restriction enzyme Hpy188III was performed in Cyt b regions to identify the species of Sika deer and Red deer. Simultaneously, recombination plasmid carrying the cyt b fragment could be cloned, sequenced, and blasted. The assay specificity and sensitivity were evaluated, and 30 batches of commercial samples were validated. The phylogenetic tree showed that the physico-chemical properties of Sika deer and Red deer variants were similar. Sufficient DNA extracts were extracted from all samples used in the improved SDS method. Establishment and optimization of a species-specific PCR reactions and PCR-RFLP system were undertaken to identify deer species in Penis et testis cervi samples. A specific PCR-RFLP pattern with three distinct products of sizes 155, 113, and 204 bp was exhibited in Sika deer species, and two distinct products of 204 and 268 bp in size were evident in Red deer species, which were significantly different from the pattern of the counterfeits or adulterants. The distinctive PCR-RFLP fingerprint pattern using the restriction enzyme Hpy188III is a rapid and reliable assay for identification of the Penis et testis cervi species.

As the final step in apoptosis, apoptotic cells (ACs) are swiftly removed by specialized phagocytes, such as macrophages, or nonprofessional phagocytes, such as epidermal cells. Genetic studies of model organisms such as Caenorhabditis elegans have helped to elucidate the mechanisms of AC clearance and the underlying causes of disorders related to the dysregulation of these pathways. C. elegans possesses six class B scavenger receptor homologs, but whether they affect apoptosis is unknown. Here, we show that only the loss of function of scav‐3, the C. elegans homolog of human lysosomal integral membrane protein‐2, resulted in a considerable accumulation of cell corpses, which was caused by a failure in degradation rather than engulfment. SCAV‐3 was found to be widely distributed and localized in lysosomes to maintain the integrity of the lysosomal membrane. Further study revealed that loss of scav‐3 had no effect on phagosome maturation or the recruitment of lysosomes to phagosomes carrying cell corpses. Moreover, we discovered that the hydrolytic enzymes contained in the lysosomes were reduced in phagosomes in scav‐3 mutants. Thus, hydrolases may leak from the damaged lysosome during phagolysosome formation due to the loss of scav‐3 function, which reduces lysosome digestion activity and thus directly contributes to the elimination of ACs.

The effect of the mixing method (normal and ethanol-assisted) on selected properties of natu-ral rubber with butadiene rubber blends (NR/BR 80/20) was investigated. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) were used to evaluate the properties. In addition, the mechanical tensile properties, tear resistance and ther-mal aging, as well as vulcanization characteristic were determined. It was found that ethanol-assisted mixing can significantly improve the mechanical properties and thermal stability of the blends as are-sult of better dispersion of additives in the rubber matrix.

Straw covering is a protective tillage measure in agricultural production, but there is relatively little research on the allelopathic effects of corn straw on weeds and foxtail millet. This experiment studied the allelopathic effects of corn straw on four weeds (Chenopodium album, Setaria viridis, Echinochloa crus-galli and Amaranthus retroflexus) in foxtail millet fields, and also measured the growth indicators of foxtail millet. The study consisted of Petri dish and field experiments. Five treatments were used in the Petri dish experiment: clear water as control (0 g/L, TCK) and four types of corn straw water extracts. They were, respectively, the stock solution (100 g/L, T1), 10 X dilution (10 g/L, T2), 50 X dilution (2 g/L, T3), and 100 X dilution (1 g/L, T4) of corn straw water extracts. Additionally, seven treatments were set up in the field experiment, consisting of three corn straw covering treatments, with covering amounts of 3000 (Z1), 6000 (Z2) and 12,000 kg/ha (Z3), and four control treatments—one treatment with no corn straw cover (CK) and three treatments involving the use of a black film to create the same shading area as the corn straw covered area, with black film coverage areas of 50% (PZ1), 70% (PZ2), and 100% (PZ3), respectively. The results showed that the corn straw water extract reduced the germination rate of the seeds of the four weeds. The T1 treatment resulted in the allelopathic promotion of C. album growth but the inhibition of S. viridis, E. crus-galli, and A. retroflexus growth. Treatments T2, T3, and T4 all induced the allelopathic promotion of the growth of the four weeds. The order of the effects of the corn straw water extracts on the comprehensive allelopathy index of the four weed seeds was as follows: C. album > S. viridis > A. retroflexus > E. crus-galli. With an increase in the corn straw mulching amount, the density and total coverage of the four weeds showed a gradual downward trend, whereas the plant control effect and fresh weight control effect showed a gradual upward trend. All indices showed the best results under 12,000 kg/ha of mulching and returning to the field. Overall, corn straw coverage significantly impacted the net photosynthetic rate and transpiration rate of foxtail millet and increased the yield of foxtail millet. Under coverages of 6000 and 12,000 kg/ha, the growth of foxtail millet is better. Based on our findings, we recommend a corn straw coverage of 12,000 kg/ha for the allelopathic control of weeds in foxtail millet fields.

Objective: To explore the effect of traditional Chinese medicine (TCM) nursing on relieving postoperative pain in patients with anorectal diseases. Method: Three English and three Chinese databases (PubMed, Embase, the Cochrane Library, the China National Knowledge Internet, Wanfang Data and the China Science and Technology Journal Database) were systematically searched for case-controlled or prospective studies evaluating the impact of TCM nursing on postoperative pain in patients with anorectal diseases from the date of library construction until June 20, 2022. The Newcastle–Ottawa Scale was adopted to evaluate the quality of the observational studies. The effect of TCM care on pain based on the Visual Analogue Scale (VAS), the effective pain relief rate, the wound healing time and the length of hospital stay were systematically analysed. Result: After a systematic search and screening, a total of 15 documents were included in this study. The systematic evaluation showed that TCM care reduced the VAS score (mean difference (MD): 1.15（95 % Confidence Interval (CI): 1.96, −1.06; P

The emerging new VOC B.1.1.529 (Omicron) variant has raised serious concerns due to multiple mutations, reported significant immune escape, and unprecedented rapid spreading speed. Currently, studies describing the neutralization ability of different homologous and heterologous booster vaccination against Omicron are still lacking. In this study, we explored the immunogenicity of COVID-19 breakthrough patients, BBIBP-CorV homologous booster group and BBIBP-CorV/ZF2001 heterologous booster group against SARS-CoV-2 pseudotypes corresponding to the prototype, Beta, Delta, and the emergent Omicron variant. Notably, at 14 days post two-dose inactivated vaccines, pVNT titre increased to 67.4 GMTs against prototype, 8.85 against Beta and 35.07 against Delta, while neutralization activity against Omicron was below the lower limit of quantitation in 80% of the samples. At day 14 post BBIBP-CorV homologous booster vaccination, GMTs of pVNT significantly increased to 285.6, 215.7, 250.8, 48.73 against prototype, Beta, Delta, and Omicron, while at day 14 post ZF2001 heterologous booster vaccination, GMTs of pVNT significantly increased to 1436.00, 789.6, 1501.00, 95.86, respectively. Post booster vaccination, 100% samples showed positive neutralization activity against Omicron, albeit illustrated a significant reduction (5.86- to 14.98-fold) of pVNT against Omicron compared to prototype at 14 days after the homologous or heterologous vaccine boosters. Overall, our study demonstrates that vaccine-induced immune protection might more likely be escaped by Omicron compared to prototypes and other VOCs. After two doses of inactivated whole-virion vaccines as the “priming” shot, a third heterologous protein subunit vaccine and a homologous inactivated vaccine booster could improve neutralization against Omicron.

Wireworms and white grubs are destructive underground pests in maize fields in China. Cyantraniliprole has good control effect on coleoptera pests. Here, we evaluated the toxicity of cyantraniliprole to the second instar larvae of Anomala corpulenta Motschulsky and third-instar of larvae of Pleonomus canaliculatus Faldermann and the effects of sublethal concentrations on the activity of antioxidant and detoxification enzymes. We also explored the efficacy of cyantraniliprole on underground pests under indoor and field conditions. The LC50 of cyantraniliprole for the third instar larvae of P. canaliculatus was 23.3712 mg/L, and that for the second instar larvae of A. corpulenta was 5.9715 mg/L. Cyantraniliprole can activate the activity of superoxide dismutase (SOD), peroxidase (POD), and glutathione S-transferase (GST) to different degrees at a sublethal dose. According to the pot experiment and the control efficacy test in the field, the indoor control effect of cyantraniliprole seed treatment on P. canaliculatus and white grubs was approximately 80%, and the maximum increase in yield achieved through cyantraniliprole application was approximately 15% in the field efficacy test. Cyantraniliprole has a strong control effect on wireworms and white grubs, so it can be used to treat seeds to control underground pests in maize fields.

This study aimed to explore the evolution of Jingdang and Famen towns near the Zhouyuan site, the capital city site of the Western Zhou Dynasty in China, to elucidate the relationship between township development and the essential ancient relics conservation areas. Based on the remote sensing satellite images from 1982 to 2022, combining with historical demographic data, this study used four methods, including land use classification, land use transfer matrix, landscape pattern center of gravity changes, and population count statistics, to study the spatial–temporal evolution of land, population, and ecology in the region over the past 40 years. The results showed that under the strict relic conservation regimen, these two towns are in a declining stage. To improve their decaying status, some potential strategies valuable for township development are proposed to balance the relationship between relic conservation and township development for their mutual benefit and coexistence.

Friction stir welding (FSW) has been adopted in the aerospace industry for fabricating structural alloys due to the low melting point and high thermal conductivity of aviation aluminum alloys. However, welding residual stresses can lead to secondary deformation in friction stir welded (FSWed) structures. Additionally, microstructural characteristics impact the crack growth rates and directions in these structures. Therefore, it is necessary to investigate the effects of residual stress and microstructure on the fatigue responses of FSWed joints. In this paper, we studied the fatigue crack growth behavior of two homogeneous and dissimilar FSWed joints with varying welding parameters, namely 2024-T3 and 7075-T6. The residual stresses were measured with the X-ray diffraction method. The dislocations and precipitates in different zones of the FSWed joints were analyzed via transmission electron microscopy (TEM). The results demonstrated that the residual stress significantly affected the fatigue crack growth rate and direction; the tensile residual stress promoted fatigue crack growth and offset the decrease in the fatigue crack growth rate that occurred due to grain refinement. The results of the microstructural analysis indicated that dislocation density and sliding resistance increased with the decrease in rotational speed and led to a decreased rate of fatigue crack propagation.

ObjectivesAssess the validity of the Chinese version of the Dominic Interactive (DI), a 91-item, video-based diagnostic screening instrument for children that assesses four internalized disorders (phobias, separation anxiety disorder, generalized anxiety disorder, and major depressive disorder) and three externalized disorders (attention-deficit/hyperactivity disorder, conduct disorder, oppositional defiant disorder).Methods(1) Compare DI-generated “probable” or “possible” diagnoses to diagnoses based on the Development and Well-Being Assessment (DAWBA) instrument in 113 psychiatric outpatients and 20 community controls. (2) Administer DI to 1,479 children from elementary schools in Tianjin.ResultsIn the validation sample, DI with DAWBA concordance was much greater for internalized disorders (mean Kappa = 0.56) than for externalized disorders (mean kappa = 0.11). The positive predictive value of DI diagnoses ranged from 0.96 (generalized anxiety disorder) to 25% (oppositional defiant disorder) and negative from 0.81 to 0.96. Using “probable” cuts provides better results. In the survey, prevalence of probable DI disorders ranged from 1.0% (conduct disorder) to 13.1% (phobias). Internal consistency of all DI items was excellent (Cronbach alpha = 0.93) and that of the seven subscales ranged from 0.64 (phobias) to 0.87 (major depressive disorder). In multilevel SEM analyses, SRMR (Standardized root mean square residual) or each of the seven diagnoses was below 0.08 and each coefficient of determination was below 0.60.ConclusionThe Chinese DI is a convenient method of screening common mental disorders in Chinese children mainly for internalized disorders, which are the most prevalent diagnoses in that population. However its high negative predictive values for externalized could be used for screening.

The immunity potency upon natural infection or vaccination is the main concern for the vaccine strategy of severe acute respiratory syndrome coronavirus 2（SARS COV-2 variant）, especially the recently reported Omicron variant (B.1.1.529). In this study, 200 recipients immunized with three doses of a COVID-19-inactivated vaccine were enrolled, whose serum samples were collected within 2 months after the third immunization. The neutralizing activity of sera against the pseudotyped Omicron variant, prototype, and Delta variant was determined. Our results demonstrated that the positive neutralization activity was 95.5% for the Omicron variant, 99.5% for the prototype, and 98.5% for the Delta variant. The geometric mean titers （GMT） for the Omicron variant was 49 and maintained sustained immune levels for 2 months, which decreased by 4.9-fold and 3.0-fold compared with the prototype (GMT, 239) and Delta variant (GMT, 148), respectively. In summary, our study demonstrated that three doses of a COVID-19-inactivated vaccine effectively yielded potent cross-neutralizing activity against the Omicron variant at 2 months after the third vaccination.

The "replication crisis" is a methodological problem in which many scientific research findings have been difficult or impossible to replicate. Because the reproducibility of empirical results is an essential aspect of the scientific method, such failures endanger the credibility of theories based on them and possibly significant portions of scientific knowledge. An instance of the replication crisis, analytic replication, pertains to reproducing published results through computational reanalysis of the authors' original data. However, direct replications are costly, time-consuming, and unrewarded in today's publishing standards. We propose that bioinformatics and computational biology students replicate recent discoveries as part of their curriculum. Considering the above, we performed a pilot study in one of the graduate-level courses we developed and taught at our University. The course is entitled Intro to R Programming and is meant for students in our Master's and PhD programs who have little to no programming skills. As the course emphasized real-world data analysis, we thought it would be an appropriate setting to carry out this study. The primary objective was to expose the students to real biological data analysis problems. These include locating and downloading the needed datasets, understanding any underlying conventions and annotations, understanding the analytical methods, and regenerating multiple graphs from their assigned article. The secondary goal was to determine whether the assigned articles contained sufficient information for a graduate-level student to replicate its figures. Overall, the students successfully reproduced 39% of the figures. The main obstacles were the need for more advanced programming skills and the incomplete documentation of the applied methods. Students were engaged, enthusiastic, and focused throughout the semester. We believe that this teaching approach will allow students to make fundamental scientific contributions under appropriate supervision. It will teach them about the scientific process, the importance of reporting standards, and the importance of openness.

The phagocytic receptor CED-1 mediates apoptotic cell recognition by phagocytic cells, enabling cell corpse clearance in Caenorhabditis elegans. Whether appropriate levels of CED-1 are maintained for executing the engulfment function remains unknown. Here, we identified the C. elegans E3 ubiquitin ligase tripartite motif containing-21 (TRIM-21) as a component of the CED-1 pathway for apoptotic cell clearance. When the NPXY motif of CED-1 was bound to the adaptor protein CED-6 or the YXXL motif of CED-1 was phosphorylated by tyrosine kinase SRC-1 and subsequently bound to the adaptor protein NCK-1 containing the SH2 domain, TRIM-21 functioned in conjunction with UBC-21 to catalyze K48-linked poly-ubiquitination on CED-1, targeting it for proteasomal degradation. In the absence of TRIM-21, CED-1 accumulated post-translationally and drove cell corpse degradation defects, as evidenced by direct binding to VHA-10. These findings reveal a unique mechanism for the maintenance of appropriate levels of CED-1 to regulate apoptotic cell clearance.

Ubiquitination, a critical post-translational modification of proteins, refers to the covalent attachment of ubiquitin to the substrate and is involved in various biological processes such as protein stability regulation, DNA damage repair, and apoptosis, among others. E3 ubiquitin ligases are essential enzymes of the ubiquitin pathway with high substrate specificity and precisely regulate specific proteins’ turnover. As one of the most well-studied forms of programmed cell death, apoptosis is substantially conserved across the evolutionary tree. The final critical stage in apoptosis is the removal of apoptotic cells by professional and non-professional phagocytes. Apoptosis and apoptotic cell clearance are crucial for the normal development, differentiation, and growth of multicellular organisms, as well as their association with a variety of inflammatory and immune diseases. In this review, we discuss the role of ubiquitination and deubiquitination in apoptosis and apoptotic cell clearance.

BackgroundAlthough evidence-based and effective treatments are available for people with major depressive disorder (MDD), a substantial number do not seek or receive help. Therefore, this study aimed to (1) investigate the total help-seeking rate and first-time help-seeking choices; (2) explore the perceived helpfulness of 23 potential sources; and (3) evaluate the factors related to help-seeking behaviors among patients with MDD.Materials and MethodsData came from the Tianjin Mental Health Survey (TJMHS), which included a representative sample of adult community residents (n = 11,748) in the Chinese municipality of Tianjin. Of these, 439 individuals were diagnosed with lifetime MDD according to the Diagnostic and Statistical Manual-fourth edition (DSM-IV) and administered a help-seeking questionnaire.ResultsIn a survey, 28.2% of patients with MDD living community reported that they had ever sought any help during their entire lifetime before the interview, with 8.2% seeking help in mental healthcare settings, 8.0% only in other healthcare settings, and 12.0% only in non-healthcare sources (e.g., family, friends, and spiritual advisor). Among help-seekers, the first help mainly was sought in non-healthcare sources (61.3%), followed by healthcare settings (25.8%) and mental healthcare settings (12.9%). The majority of MDD individuals thought the non-healthcare sources were not helpful and mental healthcare settings were helpful or possibly helpful to solve mental problems. Female, having 10–12 or higher education years, comorbid anxiety disorders were associated with increased help-seeking.ConclusionA small percentage of individuals with MDD living in community of Tianjin sought help. They preferred non-healthcare sources to healthcare settings. Demographic and clinical features were associated with help-seeking behaviors.

Abstract Background To explore the relationship between geographical differences of mortality and related risk factors in ischemic heart disease (IHD) in China. Methods Data were collected from the nationally representative China Mortality Surveillance System to calculate annual IHD mortality counts (2010–2015). Descriptive analysis was used to analyze the IHD mortality among Chinese population from 2010 to 2015. Negative binomial regression was used to investigate potential spatiotemporal variation and correlations with age, gender, urbanization, and region. Results The overall IHD mortality was 221.17/100,000, accounting for 1.51 million deaths in 2015. The standardized IHD mortality rate increased by 5.51% from 2010 to 2015 among people aged 40 years and older. Multilevel analysis indicated significant differences in gender, regions, and age. High urbanization rate (risk ratio [RR] = 0.728, 95% confidence interval [CI] = (0.631, 0.840)) and average high-density lipoprotein (HDL) (RR = 0.741, 95%CI: 0.616,0.891) were negatively associated with IHD mortality. IHD mortality was significantly higher in populations with a low rate of medical insurance coverage (RR = 1.218, 95%CI: 1.007, 1.473), as well as the average body mass index (BMI) (RR = 1.436, 95%CI: 1.135, 1.817) and systolic blood pressure (SBP) (RR = 1.310, 95%CI: 1.019, 1.684). While the relationship with current smoking rate, excessive intake of red meat, insufficient vegetable or fruits intake didn’t show the statistical significance. The negative correlation between the average sedentary time and IHD mortality was not conclusive due to the possible deviation of the data. Conclusions The mortality of IHD showed an upward trend for people aged 40 years and older in China during 2010–2015, which should be paid attention to. Therefore, some risk factors should be controlled, such as SBP, overweight/obesity. HDL is a protective factor, as well as higher urbanization rate, family income level, and medical insurance coverage.

To realize the unmanned automation of the full mechanized caving, the bottleneck problem of coal-gangue interface detection in top coal caving must be solved first. Targeting coal-gangue interface detection on fully mechanized mining face, an alternative scheme to detect coal-gangue interface based on vibration signal analysis of the tail boom support of the longwall mining machine. It is found that when coal and gangue fall, the characteristics of vibration signals generated by coal and gangue shocking the tail boom are different. First, EEMD algorithm is used to decompose the original vibration signals into intrinsic mode functions (IMFs). Each IMF represents the distribution of energy from high to low. EEMD algorithm can restrain the mode mixing phenomenon caused by empirical mode decomposition (EMD). The energy of vibration signals will change in different frequency bands when the top-coal fall down or the coal-gangue fall down. According the information theory, we define EEMD energy entropy to describe this change. Experimental results show that EEMD energy entropy of top-coal caving is always greater than that of coal-gangue caving. Thus, the Mahalanobis distance metric method based on EEMD energy entropy is proposed for coal-gangue interface detection. The results show the proposed method can be used as a robust empirical method for coal-gangue interface detection.

Long non-coding RNAs (lncRNAs) play a significant role in post-translational modifications of proteins, yet the importance of lncRNAs for SUMOylation is unknown. rhabdomyosarcoma 2 associated transcript (RMST) expression in glioma tissues and normal brain tissues was measured by quantitative real-time PCR and in situ hybridization. The functional roles of RMST in astrocytomas were demonstrated by a series of in vitro experiments. The potential mechanisms of RMST for SUMOylation were investigated by RNA immunoprecipitation, RNA pull-down, western blotting, and coimmunoprecipitation assays. We first demonstrated the oncogenic activity of lncRNA RMST by inhibiting glioma cells mitophagy. We also first determined that RMST is an enhancer of FUS SUMOylation, especially boosting SUMO1 modification at K333. SUMOylation induced by RMST contributes to the interaction between FUS and heterogeneous nuclear ribonucleoprotein D (hnRNPD) and stabilized their expression and cells mitophagy. Importantly, lncRNA RMST could serve as a promising prognostic factor for glioma patients. Our results demonstrated a previously unknown function of lncRNAs worked as an enhancer in FUS SUMOylation, and RMST will be a significant guide for the development of medications targeting gliomas. Keywords: lncRNA, SUMOylation, oncogene, GBM

Abstract Objective The traditional approaches for diagnosing catheter-related bloodstream infection(CRBSI) is time consuming, which could not meet the clinical requirement. Our aim was to investigate the value of serum procalcitonin(PCT) in predicting CRBSI in first-ever acute ischemic stroke patients with central venous catheters (CVCs). Methods This was a retrospective study. First-ever acute ischemic stroke patients hospitalized in neurological intensive care unit(NICU) of Aerospace Center Hospital and NICU of Beijing Chaoyang Hospital during January 2010 and December 2017 with clinically suspected CRBSI were enrolled. Peripheral blood white blood cell (WBC) count, neutrophils percentage(NE%), the levels of serum PCT, dwell time of catheterization and outcome of the patients were collected. According to the diagnosis of CRBSI or not, they were divided into CRBSI group and no CRBSI group. We used receiver operating characteristic curve (ROC) to evaluate the value of serum PCT levels in predicting CRBSI in patients with clinically suspected CRBSI. Results Forty-five patients with suspected CRBSI were included in this study, and 13 patients were diagnosed with CRBSI. Comparing to those in no CRBSI group, the maximum body temperature (Tmax) (p = 0.036) and the PCT levels (P = 0.013) in CRBSI group were both significantly higher. The area under ROC of the serum PCT levels and the Tmax to predict the CRBSI were 0.803 (0.95CI,0.660–0.946) and 0.680 (0.95CI,0.529–0.832) respectively. The PCT cut-off value was 0.780 ng/ml, with the sensitivity 69.23%, specificity 87.50%, positive predictive values 69.23% and negative predictive values 87.50%. Conclusion It could be helpful to adopt PCT as a rapid diagnostic biomarker for first-ever acute stroke patients with suspected CRBSI.

Xyloglucan is a quantitatively major polysaccharide in the primary cell walls of flowering plants and has been reported to affect plants’ ability to tolerate toxic elements. However, it is not known if altering the amounts of xyloglucan in the wall influences the uptake and translocation of inorganic arsenic (As). Here, we identified two Nicotiana tabacum genes that encode xyloglucan-specific xylosyltransferases (XXT), which we named NtXXT1 and NtXXT2. We used CRISPR-Cas9 technology to generate ntxxt1, ntxxt2, and ntxxt1/2 mutant tobacco plants to determine if preventing xyloglucan synthesis affects plant growth and their ability to accumulate As. We show that NtXXT1 and NtXXT2 are required for xyloglucan biosynthesis because no discernible amounts of xyloglucan were present in the cell walls of the ntxxt1/2 double mutant. The tobacco double mutant (ntxxt1/2) and the corresponding Arabidopsis mutant (atxxt1/2) do not have severe growth defects but do have a short root hair phenotype and a slow growth rate. This phenotype is rescued by overexpressing NtXXT1 or NtXXT2 in atxxt1/2. Growing ntxxt mutants in the presence of AsIII or AsV showed that the absence of cell wall xyloglucan affects the accumulation and translocation of As. Most notably, root retention of As increased substantially and the amounts of As translocated to the shoots decreased in ntxxt1/2. Our results suggest that xyloglucan-deficient plants provide a strategy for the phytoremediation of As contaminated soils.

Background: Concerns are increasing over the mechanisms of drug resistance pathogens among non-gonococcal urethritis (NGU) or cervicitis. The study aims to explore the distribution of Ureaplasm urealyticum (U. urealyticum) and Mycoplasma homins (M. homins) isolates, characteristics of multidrug resistance, and the underlying mechanism to allow clinicians to deliver rational therapy for NGU. Methods: Samples from cervical secretions of 246 patients with NGU were collected. Mycoplasma culture and drug susceptibility tests were performed, respectively. The resistance genes were detected by multiplex Polymerase Chain Reaction (PCR), and the PCR products were cloned and sequenced. Results: Out of 246 samples, the overall prevalence of U. urealyticum and/or M. hominis infection was 39.02% (96/246). In 96 culture positive samples, the overall infection rate of U. urealyticum was higher than that of the single M. hominis (46.87% vs. 28.13%) (p < 0.05), and the coinfection rate was 25.00% (24/96). Each U. urealyticum and M. hominis isolate exhibited resistance to at least three types of antimicrobial agents (manifest by more than 70% resistance to erythromycin, tetracycline, ciprofloxacin, and spiramycin, followed by ofloxacin, roxithromycin, azithromycin and josamycine (with resistance thereto of more than 50%)). More than 80% of U. urealyticum and M. hominis isolates were susceptible to minomycine and doxycycline, whereas 81.16% and 77.44% of both U. urealyticum and M. hominis isolates were also susceptible to minomycine and doxycycline. Surprisingly, the resistance rate of the mixed infection was higher that of erythromycin, tetracycline and ciprofloxacin comparison to the single infection (p < 0.05). All tetracycline-resistant isolates carried the tetM gene and 50% of erythromycin-resistant isolates carried the ermA gene. Conclusions: Among outpatients with recurrent NGU, the U. urealyticum infection dominated, followed by M. hominis, mixed U. urealyticum and M. hominis infection. Minomycine and doxycycline are recommended for empirical clinical treatment. The determination of U. urealyticum and M. hominis infection, antibiotic susceptibility testing is crucial for effective therapy.

Reciprocal toolpaths with four-axis simultaneous motion of five-axis or four-axis machine tools are commonly used in the machining of blades which are widely applied in high-end equipment such as the aero-engine and the marine steam turbine. Due to the complex geometry of the blades, the tool orientation always suffers from frequent swing for this kind of toolpaths, which induces unnecessary acceleration/deceleration of the feed axes, thus degrading processing efficiency and quality. Although there are tool orientation optimization methods aiming at solving the above problem, they are mainly proposed for universal processing of the toolpaths for complex surfaces. Different from them, this paper proposes a piecewise decoupling tool orientation re-scheduling method for this kind of toolpath specifically, which takes full use of the characteristic of the reciprocal toolpaths of the blades, and takes the monotonous variation of rotation axes as an additional constraint. The re-scheduling process is realized based on the construction of a S-θ plane, where the scheduling problem is converted to the adjustment of a S-θ curve inside a feasible channel. Through two procedures, namely linearization scheduling and control-point assigning-based smoothing, the tool orientation path expressed by the S-θ curve can be effectively scheduled in a piecewise manner, and the smoothness between two adjacent pieces of the toolpaths can be ensured directly. The whole algorithm is lightweight and does not involve complex iterative operations or functional optimization solutions. Simulation and experimental tests verify the feasibility and superiority of this method. The results show that the machining efficiency of the blade is improved by 24.5%, due to the reduction of the requirement on highest feed-axis kinematics parameters after rescheduling. In addition, compared with the existing methods, the proposed method not only can improve the dynamics of feed axes in multi-axis machining, but also has advantages in computational complexity and monotonic variation property of the tool orientation.

A decentralized credit system was proposed and its construction application was given.Decentralized credit system could be constructed by expanding the transaction structure of “digital currency commodity” based on block chain,expanding the function of consensus protocol and adding specific accounts.Also,the decentralized credit system was applied to the PKI enhancement and supervision system IKP so that IKP system did not need global fund in operation.Moreover,by introducing the hierarchical “virtual currency commodity” supply adjustment mechanism in the decentralized credit system to alleviate the difficulty of regulating the “virtual currency commodity” supply of “digital currency commodity” based on block chain,the precise “virtual currency commodity” supply regulation can be achieved.

As an important medicine homologous food, Chinese jujube is rich in nutrition and medicinal value. To enhance the bioactive compounds level of Chinese jujube products, three kinds of fungi strains (Rhizopus oryzae, Aspergillus niger and Monascus purpureus) were firstly selected to evaluate their effects on total soluble phenolic compounds (TSPC) and total soluble flavonoids compounds (TSFC) contents during liquid state fermentation of Chinese jujube. As the best strain, the highest contents of TSPC and TSFC could increase by 102.1% (26.02 mg GAE/g DW) and 722.8% (18.76 mg RE/g DW) under M. purpureus fermentation when compared to the unfermented sample, respectively. Qualitative and quantitative analysis of individual polyphenol compounds indicated that proto-catechuic acid, p-hydroxybenzoic acid and chlorogenic acid showed the highest level in the fer-mented Chinese jujube at the 7th day, which was enhanced by 16.72-, 14.05- and 6.03-fold when compared to the control, respectively. Combining with RNA sequencing, function annotation of CAZymes database and polyphenol profiling, three potential transformation pathways of poly-phenol compounds were proposed in the fermented Chinese jujube by M. purpureus, such as the conversion of insoluble bound phenolic acids, rutin and anthocyanin degradation. These findings would be beneficial for better understanding of the biotransformation mechanism of polyphenol compounds in fungi fermentation.

Background: The residual SYNTAX score (RSS) is considered a powerful prognostic indicator for determining a reasonable revascularization strategy in patients undergoing percutaneous coronary intervention (PCI), but the absence of clinical parameters is one of the limitations of RSS, especially in the chronic renal insufficiency (CRI) comorbidity setting. The present work aimed to investigate the incremental prognostic value of clinical residual SYNTAX score (CRSS) compared with RSS in CRI cases after PCI.Methods: Totally 2,468 consecutive CRI cases who underwent PCI from January 2014 to September 2017 were included in this retrospective analysis. CRSS was obtained by multiplying RSS by the modified ACEF score. Individuals with CRSS >0 were considered to have incomplete revascularization and stratified by CRSS tertiles, the remaining cases constituted the complete revascularization (CR) group. The outcomes between these groups were compared.Results: At a median follow-up of 3 years, compared with CR group, individuals with CRSS >12 showed elevated rates of all clinical outcomes, and those with CRSS ≤ 12 showed similar all-cause and cardiac mortality rates. In multivariable analysis, CRSS was a powerful independent predictive factor of all clinical outcomes. The net reclassification improvement levels of CRSS over RSS for all-cause and cardiac mortality rates were 10.3% (p = 0.007) and 16.4% (p < 0.001), respectively. Compared with RSS, CRSS markedly ameliorated all-cause and cardiac mortality risk stratification.Conclusions: Compared with RSS, CRSS has incremental predictability for long-term all-cause and cardiac mortality in CRI cases following PCI.

Exosomes are natural nanoscale bilayer phospholipid vesicles that can be secreted by almost all types of cells and are detected in almost all types of body fluids. Exosomes are effective mediators of cell–cell signaling communication because of their ability to carry and transfer a variety of bioactive molecules, including non-coding RNAs. Non-coding RNAs have also been found to exert strong effects on a variety of biological processes, including tumorigenesis. Many researchers have established that exosomes encapsulate bioactive non-coding RNAs that alter the biological phenotype of specific target cells in an autocrine or a paracrine manner. However, the mechanism by which the producer cells package non-coding RNAs into exosomes is not well understood. This review focuses on the current research on exosomal non-coding RNAs, including the biogenesis of exosomes, the possible mechanism of sorting non-coding RNAs, their biological functions, and their potential for clinical application in the future.

Background Despite wide usage across all areas of medicine, it is uncertain how useful standard reference ranges of laboratory values are for critically ill patients.Objectives The aim of this study is to assess the distributions of standard laboratory measurements in more than 330 selected intensive care units (ICUs) across the USA, Amsterdam, Beijing and Tarragona; compare differences and similarities across different geographical locations and evaluate how they may be associated with differences in length of stay (LOS) and mortality in the ICU.Methods A multi-centre, retrospective, cross-sectional study of data from five databases for adult patients first admitted to an ICU between 2001 and 2019 was conducted. The included databases contained patient-level data regarding demographics, interventions, clinical outcomes and laboratory results. Kernel density estimation functions were applied to the distributions of laboratory tests, and the overlapping coefficient and Cohen standardised mean difference were used to quantify differences in these distributions.Results The 259 382 patients studied across five databases in four countries showed a high degree of heterogeneity with regard to demographics, case mix, interventions and outcomes. A high level of divergence in the studied laboratory results (creatinine, haemoglobin, lactate, sodium) from the locally used reference ranges was observed, even when stratified by outcome.Conclusion Standardised reference ranges have limited relevance to ICU patients across a range of geographies. The development of context-specific reference ranges, especially as it relates to clinical outcomes like LOS and mortality, may be more useful to clinicians.

It has been suggested that Staufen (Stau) is key in controlling the variability of the posterior boundary of the Hb anterior domain (xHb). However, the mechanism that underlies this control is elusive. Here, we quantified the dynamic 3D expression of segmentation genes in Drosophila embryos. With improved control of measurement errors, we show that the xHb of stau– mutants reproducibly moves posteriorly by 10% of the embryo length (EL) to the wild type (WT) position in the nuclear cycle (nc) 14, and that its variability over short time windows is comparable to that of the WT. Moreover, for stau– mutants, the upstream Bicoid (Bcd) gradients show equivalent relative intensity noise to that of the WT in nc12–nc14, and the downstream Even-skipped (Eve) and cephalic furrow (CF) show the same positional errors as these factors in WT. Our results indicate that threshold-dependent activation and self-organized filtering are not mutually exclusive and could both be implemented in early Drosophila embryogenesis.

Epithelial ovarian cancer (EOC) is the most malignant gynecological carcinoma and is of a high incidence of death due to detection at late stages when metastasis already occurs. However, the mechanism underlying metastasis of EOC remains unclear. Analysis of the open database and experiments with immunochemistry showed that LRRC4 is lowly expressed in high-grade serous ovarian cancer (HGSC) cells and during EOC metastasis. The 3D cell culture system and the orthotopic ovarian xenograft model infected with LRRC4-containing adeno-associated virus serotype 9 (AAV9) were used to confirm collective invasion and metastasis of cells in vitro and in vivo. Phos-tag SDS-PAGE was used to detect the phosphorylation of LRRC4 and PIK3R1. A number of experiments with methods such as co-immunoprecipitation and immunoblotting were performed to explore the mechanism for the actions of LRRC4 and PIK3R1 in EOC metastasis. An inverse correlation between LRRC4 and E-cadherin expression was detected in the regions of invasion in primary EOC tissues and metastatic ascites. LRRC4 binds to the cSH2 domain of PIK3R1 and inhibits the activity of PIK3R1, without disrupting the physical interactions between PIK3R1 and PIK3CA. LRRC4 inhibits EOC metastasis by targeting E-cadherin-dependent collective cell invasion and does so by inhibiting the PIK3R1-mediated AKT/GSK3β/β-catenin signaling pathway. LRRC4 functions as a tumor suppressor gene to inhibit EOC collective invasion and metastasis in vitro and in vivo and does so by directly binding to the cSH2 domain of PIK3R1 to exert its regulatory function. Our findings provide a potential novel approach for metastasis prognosis and a new strategy for the treatment of EOC.

Background: The aim of this study was to investigate the prevalence and characteristics of SCCmec genotypes and drug resistance of methicillin-resistant Staphylococcus aureus (MRSA) isolated from intensive care units (ICU) at obstetrics & gynaecology departments in a tertiary hospital. Methods: MRSA obtained from patients admitted to the ICU were isolated and identified by using the Vitek 2 Compact System with GP21 342 cards. Antimicrobial susceptibility profiles and MRSA screening were determined by using the broth microdilution method according to CLSI guidelines. Determination of resistant genes and SCCmec genotypes were performed by multiplex PCR. Results: Of the 283 patients evaluated, 120 (42.4%) isolates were phenotypically and genotypically confirmed to be MRSA. Among 120 strains, 15 (12.5%) strains were SCCmec type II, 96 (80%) strains were SCCmec type III and 9 (7.5%) strains were undifferentiated type. All MRSA strains were recognized as multidrug resistant, exhibiting 100% resistance to cefoxitin and oxacillin, followed by erythromycin and levofloxacin (more than 80% and 90% respectively). Different SCCmec genotypes in MRAS isolates showed distinct antimicrobial agent patterns. SCCmec type II was highly resistant to clindamycin (93.3%) with lower resistance to tetracycline (26.7%) with SCCmec type III being highly resistant to gentamicin (91.7%). Undifferentiated strains were resistant to Cotrimoxazole (77.8%). There was a statistical difference among type II, type III and Undifferentiated strains (P < 0.05). Of interest, a high prevalence of resistance to rifampicin (more than 75%) was also noted in the hospital. With different SCCmec genotypes, MRSA isolates were sensitive to minocycline, quinupristin, teicoplanin, vancomycin and nitrofurantoin. Conclusions: Our data indicate that SCCmec type II and SCCmec type III of MRSA are circulating in the ICU and constitute a major source for the infection spread. It is necessary to increase surveillance of MRSA in the ICU and develop adequate infection prevention strategies.

Abstract Background Despite the overwhelming number of investigations on AKT, little is known about lncRNA on AKT regulation, especially in GBM cells. Methods RNA-binding protein immunoprecipitation assay (RIP) and RNA pulldown were used to confirm the binding of LINC00470 and fused in sarcoma (FUS). Confocal imaging, co-immunoprecipitation (Co-IP) and GST pulldown assays were used to detect the interaction between FUS and AKT. EdU assay, CCK-8 assay, and intracranial xenograft assays were performed to demonstrate the effect of LINC00470 on the malignant phenotype of GBM cells. RT-qPCR and Western blotting were performed to test the effect of LINC00470 on AKT and pAKT. Results In this study, we demonstrated that LINC00470 was a positive regulator for AKT activation in GBM. LINC00470 bound to FUS and AKT to form a ternary complex, anchoring FUS in the cytoplasm to increase AKT activity. Higher pAKT activated by LINC00470 inhibited ubiquitination of HK1, which affected glycolysis, and inhibited cell autophagy. Furthermore, higher LINC00470 expression was associated with GBM tumorigenesis and poor patient prognosis. Conclusions Our findings revealed a noncanonical AKT activation signaling pathway, i.e., LINC00470 directly interacts with FUS, serving as an AKT activator to promote GBM progression. LINC00470 has an important referential significance to evaluate the prognosis of patients.

Abstract Membrane-bound transcription factors (MTFs) are transcription factors (TFs) that are anchored in membranes in a dormant state. Activated by external or internal stimuli, MTFs are released from parent membranes and are transported to the nucleus. Existing research indicates that some plasma membrane (PM)-bound proteins and some endoplasmic reticulum (ER) membrane-bound proteins have the ability to enter the nucleus. Upon specific signal recognition cues, some PM-bound TFs undergo proteolytic cleavage to liberate the intracellular fragments that enter the nucleus to control gene transcription. However, lipid-anchored PM-bound proteins enter the nucleus in their full length for depalmitoylation. In addition, some PM-bound TFs exist as full-length proteins in cell nucleus via trafficking to the Golgi and the ER, where membrane-releasing mechanisms rely on endocytosis. In contrast, the ER membrane-bound TFs relocate to the nucleus directly or by trafficking to the Golgi. In both of these pathways, only the fragments of the ER membrane-bound TFs transit to the nucleus. Several different nuclear trafficking modes of MTFs are summarized in this review, providing an effective supplement to the mechanisms of signal transduction and gene regulation. Moreover, targeting intracellular movement pathways of disease-associated MTFs may significantly improve the survival of patients.

Abstract Background SIX homeobox 3 (SIX3) is a member of the sine oculis homeobox transcription factor family. It plays a vital role in the nervous system development. Our previous study showed that the SIX3 gene is hypermethylated, and its expression is decreased in astrocytoma, but the role of SIX3 remains unknown. Methods Chromatin-immunoprecipitation (ChIP) and luciferase reporter assay were used to confirm the binding of SIX3 to the promoter regions of aurora kinase A (AURKA) and aurora kinase B (AURKB). Confocal imaging and co-immunoprecipitation (Co-IP) were used to detect the interaction between AURKA and AURKB. Flow cytometry was performed to assess the effect of SIX3 on cell cycle distribution. Colony formation, EdU incorporation, transwell, and intracranial xenograft assays were performed to demonstrate the effect of SIX3 on the malignant phenotype of astrocytoma cells. Results SIX3 is identified as a novel negative transcriptional regulator of AURKA and AURKB, and it decreases the expression of AURKA and AURKB in a dose-dependent manner in astrocytoma cells. Importantly, interactions between AURKA and AURKB stabilize and protect AURKA/B from degradation, and overexpression of SIX3 does not affect these interactions; SIX3 also acts as a tumor suppressor, and it increases p53 activity and expression at the post-translational level by the negative regulation of AURKA or AURKB, reduces the events of numerical centrosomal aberrations and misaligned chromosomes, and significantly inhibits the proliferation, invasion, and tumorigenesis of astrocytoma in vitro and in vivo. Moreover, experiments using primary cultured astrocytoma cells indicate that astrocytoma patients with a low expression of SIX3 and mutant p53 are more sensitive to treatment with aurora kinase inhibitors. Conclusion SIX3 is a novel negative transcriptional regulator and acts as a tumor suppressor that directly represses the transcription of AURKA and AURKB in astrocytoma. For the first time, the functional interaction of AURKA and AURKB has been found, which aids in the protection of their stability, and partially explains their constant high expression and activity in cancers. SIX3 is a potential biomarker that could be used to predict the response of astrocytoma patients to aurora kinase inhibitors.

Abstract Circular RNAs, a novel class of endogenous noncoding RNAs, are characterized by their covalently closed loop structures without a 5′ cap or a 3′ Poly A tail. Although the mechanisms of circular RNAs’ generation and function are not fully clear, recent research has shown that circular RNAs may function as potential molecular markers for disease diagnosis and treatment and play an important role in the initiation and progression of human diseases, especially in tumours. This review summarizes some information about categories, biogenesis, functions at the molecular level, properties of circular RNAs and the possibility of circular RNAs as biomarkers in cancers.

Circular RNAs (circRNAs) were discovered in the 1970s, but they have drawn increasing attention in recent years. Currently, we know that circRNAs are not “wrongly spliced” during transcription but play important roles in the initiation and development of various diseases, including cancers. Recently, a growing number of studies have suggested that cancer stem cells (CSCs) may contribute to the origination and maintenance of cancers. This review briefly introduces the major functions of circRNAs, including interacting with other noncoding RNAs, competing with pre-mRNA splicing, binding with proteins to form a scaffold, promoting protein nuclear translocation and even translating proteins in a cap-independent manner. Furthermore, we describe the regulatory mechanism of circRNAs in CSC phenotypes and discuss the potential clinical applications of circRNAs in CSC-targeted therapy, including functioning as new biomarkers, acting as vaccines and breaking the therapeutic resistance of CSCs. Finally, we discuss the major limitations and challenges in the field, which will be beneficial for the future clinical use of circRNAs.

CircRNAs (circular RNAs) are a class of RNAs generated from circularization with multiple novel functions. Recent studies have revealed the aberrant expression and aberrant functions of circRNAs in various tumors; thus, circRNAs have been recognized as promising cancer biomarkers. However, the underlying mechanisms behind their aberrant expression and functions remain unclear. In this review, we discuss at length the cancer-specific deregulation of circRNAs and the potential underlying aberrant events in circRNA biogenesis, localization and removal in cancer cells.