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Dynamic properties are essential for microtubule (MT) physiology. Current techniques for in vivo imaging of MTs present intrinsic limitations in elucidating the isotype-specific nuances of tubulins, which contribute to their versatile functions. Harnessing the power of the AlphaFold2 pipeline, we engineered a strategy for the minimally invasive fluorescence labeling of endogenous tubulin isotypes or those harboring missense mutations. We demonstrated that a specifically designed 16-amino acid linker, coupled with sfGFP11 from the split-sfGFP system and integration into the H1-S2 loop of tubulin, facilitated tubulin labeling without compromising MT dynamics, embryonic development, or ciliogenesis in Caenorhabditis elegans. Extending this technique to human cells and murine oocytes, we visualized MTs with the minimal background fluorescence and a pathogenic tubulin isoform with fidelity. The utility of our approach across biological contexts and species set an additional paradigm for studying tubulin dynamics and functional specificity, with implications for understanding tubulin-related diseases known as tubulinopathies. GFP-tagged tubulins have been widely used to monitor and visualize tubulin isotypes, but this is known to interfere with their cellular functions. This study describes a functional labeling strategy, guided by AlphaFold2 structural predictions, to label endogenous tubulins across diverse species while preserving functionality. [ABSTRACT FROM AUTHOR]

Hydraulic fracturing technology is an effective way to develop tight sandstone reservoirs with low porosity and permeability. The tight sandstone reservoir is heterogeneous and the heterogeneity characteristics has an important influence on fracture propagation. To investigate hydraulic fracture performance in heterogeneous tight reservoir, the X-ray diffraction experiments are carried out, the Weibull distribution method and finite element method are applied to establish the uniaxial compression model and the hydraulic fracture propagation model of heterogeneous tight sandstone. Meanwhile, the sensitivity of different heterogeneity characterization factors and the multi-fracture propagation mechanism during hydraulic fracture propagation is analyzed. The results indicate that the pressure transfer in the heterogeneous reservoir is non-uniform, showing a multi-point initiation fracture mode. For different heterogeneity characterization factors, the heterogeneity characteristics based on elastic modulus are the most sensitive. The multi-fracture propagation of heterogeneous tight sandstone reservoir is different from that of homogeneous reservoir, the fracture propagation morphology is more complex. With the increase of stress difference, the fracture propagation length increases. With the increase of injection rate, the fracture propagation length increases. With the increase of cluster spacing, the propagation length of multiple fractures tends to propagate evenly. This study clarifies the influence of heterogeneity on fracture propagation and provides some guidance for fracturing optimization of tight sandstone reservoirs. [ABSTRACT FROM AUTHOR]

Background: Tacheng tick virus 2 (TcTV-2) is an emerging tick-borne virus belonging to the genus Uukuvirus in the family Phenuiviridae. Initially isolated in 2019 from a patient in Xinjiang Uygur Autonomous Region (XUAR), northwestern China, who developed fever and headache after a tick bite, TcTV-2 was concurrently molecularly detected in hard ticks across various countries, including China, Kazakhstan, Romania, and Turkey. This study conducted a retrospective epidemiological investigation of TcTV-2 infection. Methodology: In this retrospective cohort study, we collected samples from 47 tick-bitten patients, 984 herdsmen, 7 Asian badgers, 13 red foxes, and 168 Hyalomma asiaticum tick egg batches. Patients' samples were primarily analyzed by using high-throughput sequencing, targeting the V3-V4 region of the bacterial 16S rRNA gene and viral cDNA libraries. Typical tick-borne pathogens were further confirmed using RT-PCR and detected in Asian badgers, red foxes and Hy. asiaticum tick egg batches. We also conducted enzyme-linked immunosorbent assay (ELISA) to detected specific IgM and IgG antibodies against TcTV-2 in herdsmen. Phylogenetic analysis was performed to genetically characterize TcTV-2 detected in this study. Principal findings: TcTV-2 was detected in various samples, including blood, urine, and throat swabs from 12.77% (6/47) tick-bitten patients. It was found in blood samples of 14.29% (1/7) of wild badgers, 7.69% (1/13) of red foxes, and 13.69% (23/168) of Hy. asiaticum egg batches. Furthermore, ELISA results revealed that 9.55% (94/984) of the serum samples (34 from males and 60 from females) were tested positive for TcTV-2-specific IgG, while 2.95% (29/984, 7 males and 22 females) showed positivity for TcTV-2-specific IgM. Additionally, 1.02% (10/984, 4 males and 6 females) of the sera tested positive for both TcTV-2-specific IgM and IgG. Phylogenetic analysis indicated that the TcTV-2 strains detected in this study were genetically similar, regardless of their origin and host species. Conclusions: Clinical symptoms of TcTV-2 infection in patients are nonspecific, with common symptoms including headache, fever, asthenia, vomiting, myalgia, rash, and meningitis-like signs. TcTV-2 can be detected in blood, urine, and throat swab samples of infected patients. Among local herdsmen, 9.55% tested positive for TcTV-2-specific IgG and 2.95% for TcTV-2-specific IgM. Importantly, TcTV-2 can be transovarially transmitted in Hy. asiaticum ticks, and the Asian badgers and red foxes are potential reservoirs of TcTV-2. Author summary: Tacheng tick virus 2 was initially identified in China through a metagenomic analysis of ticks. A patient bitten by a tick was subsequently found to be infected with the virus, suggesting an association with human febrile disease. Subsequent detections of TcTV-2 in various tick species have been reported in Kazakhstan, Romania, Turkey, Poland, Ukraine, and Georgia. However, the infection dynamics of this emerging tick-borne virus in humans and animals remain unclear. In this study, we identified 6 additional patients infected with TcTV-2, presenting with nonspecific clinical symptoms such as fever, asthenia, vomiting, myalgia, rash, and signs resembling meningitis. TcTV-2 was detectable in blood, urine, and throat swabs. Moreover, 9.55% of local herdsmen tested positive for TcTV-2-specific IgG and 2.95% tested positive for specific IgM. We also identified Asian badgers and red foxes as potential animal reservoirs, highlighting that TcTV-2 can be transovarially transmitted in Hyalomma asiaticum ticks. These findings significantly contribute to our understanding of the infection and transmission dynamics of this emerging tick-borne virus. [ABSTRACT FROM AUTHOR]

Partially encased concrete (PEC) has better mechanical properties as a structure where steel and concrete work together. Due to the increasing amount of construction waste, recycled aggregate concrete (RAC) is being considered by more people. However, although RAC has more points, the performance is inferior to natural aggregate concrete (NAC). To narrow or address this gap, lightweight, high-strength and corrosion-resistant CFRP can be used, also protecting the steel flange of the PEC structure. Therefore, carbon fiber reinforced polymer (CFRP) confined partially encased recycled coarse aggregate concrete columns were studied in this paper. With respect to different slenderness ratios, recycled coarse aggregate(RCA) replacement ratios, and number of CFRP layers, the performance of the proposed CFRP restrained columns are reported. The RCA replacement ratio is analyzed to be limited negative impact on the bearing capacity, generally within 6%. As for the slenderness ratio, the bearing capacity increased with it. However, wrapping CFRP significantly increased the bearing capacity. Considering the arch factor, a simple formula for calculating the ultimate strength of CFRP-confined partially encased RAC columns is developed based on EC4 and GB50017-2017. By comparison with the experimental values, the error is within 10%. [ABSTRACT FROM AUTHOR]

The corrosion resistance of FRP-reinforced ordinary concrete members under the combined action of harsh environments (i.e., alkaline or acidic solutions, salt solutions) and freeze-thaw cycles is still unclear. To study the mechanical and apparent deterioration of carbon/basalt/glass/aramid fiber cloth reinforced concrete under chemical and freeze-thaw coupling. Plain concrete blocks and FRP-bonded concrete blocks were fabricated. The tensile properties of the FRP sheet and epoxy resin sheet before and after chemical freezing, the compressive strength of the FRP reinforced test block, and the bending capacity of the prismatic test block pasted with FRP on the prefabricated crack side were tested. The deterioration mechanism of the test block was analyzed through the change of surface photos. Based on the experimental data, the Lam-Teng constitutive model of concrete reinforced by alkali-freeze coupling FRP is modified. The results indicate that, in terms of apparent properties, with the increase in the duration of chemical freeze-thaw erosion, the surface of epoxy resin sheets exhibits an increase in pores, along with the emergence of small cracks and wrinkles. The texture of FRP sheets becomes blurred, and cracks and wrinkles appear on the surface. In terms of failure modes, as the number of chemical coupling erosion cycles increases, the location of failure in epoxy resin sheets becomes uncertain, and the failure plane tilts towards the direction of the applied load. The failure mode of FRP sheets remains unchanged. However, the bonding strength between FRP sheets and concrete decreases, resulting in a weakened reinforcement effect. In terms of mechanical properties, FRP sheets undergo the most severe degradation in the coupled environment of acid freeze-thaw cycles. Among them, GFRP experiences the largest degradation in tensile strength, reaching up to 30.17%. In terms of tensile performance, the sheets rank from highest to lowest as follows: CFRP, BFRP, AFRP, and GFRP.As the duration of chemical freeze-coupled erosion increases, the loss rate of compressive strength for specimens bonded with CFRP is the smallest (9.62% in salt freeze-thaw environment), while the loss rate of bearing capacity is higher for specimens reinforced with GFRP (33.8% in acid freeze-thaw environment). In contrast, the loss rate of bearing capacity is lower for specimens reinforced with CFRP (13.6% in salt freeze-thaw environment), but still higher for specimens reinforced with GFRP (25.8% in acid freeze-thaw environment). [ABSTRACT FROM AUTHOR]

Introduction: The Electronic Nicotine Delivery Systems (ENDS) industry recently introduced non-tobacco nicotine (NTN), which is not tobacco-derived and is often marketed as "tobacco-free nicotine." Given its novelty, it is important to understand where young adults learn about NTN ENDS. This study examined sources of exposure to NTN ENDS and relationships with NTN ENDS use and susceptibility. Methods: We analyzed online survey data collected in Fall 2021 from 642 young adults (18–25 years) who had heard of NTN ENDS. We assessed 9 sources of NTN ENDS exposure (e.g., retail stores, social media) and examined associations between sources of exposure and NTN current (past-month) use, lifetime (non-current) use, and susceptibility to use, adjusting for demographics and other tobacco product use. Results: Participants reported current NTN ENDS use (37.4%), lifetime use (12.0%), susceptibility (18.5%), or no susceptibility to use (32.1%). The most common sources of NTN ENDS exposure were retail stores (87.7%) and social media (81.0%). Exposure to NTN ENDS via social media was associated with greater odds of current NTN ENDS use (vs. no susceptibility) (aOR = 1.83, 95%CI: 1.02–3.28). Exposure via online streaming platforms was associated with greater odds of current (aOR = 1.75, 95%CI: 1.08–2.82) and lifetime NTN ENDS use (aOR = 2.42, 95%CI: 1.25–4.68). Conclusions: Young adults were exposed to and learned about NTN ENDS from diverse sources, primarily retail shops and social media. Further, exposure via social media and streaming platforms were associated with NTN ENDS use. Future studies should explore the content of NTN information from various sources to inform prevention efforts. [ABSTRACT FROM AUTHOR]

Objective: To investigate the associations of Insulin-like growth factor-II (IGF2) gene, Insulin-like growth factor-II receptor (IGF2R) gene and Insulin-like growth factor-II binding protein 2 (IGF2BP2) gene polymorphisms with the susceptibility to gestational diabetes mellitus (GDM) in Chinese population. Methods: A total of 1703 pregnant women (835 GDM and 868 Non-GDM) were recruited in this case-control study. All participants underwent prenatal 75 g oral glucose tolerance test (OGTT) examinations during 24–28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Genotyping of candidate SNPs (IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs1374910, rs11705701, rs6777038, rs16860234, rs7651090) was performed on Sequenom MassARRAY platform. Logistic regression analysis was conducted to investigate the associations between candidate SNPs and risk of GDM. In addition, multifactor dimensionality reduction (MDR) method was applied to explore the effects of gene-gene interactions on GDM risk. Results: There were significant distribution differences between GDM group and non-GDM group in age, pre-pregnancy BMI, education level and family history of diabetes (P < 0.05). After adjusted for age, pre-pregnancy BMI, education level and family history of diabetes, there were no significant associations of the candidate SNPs polymorphisms and GDM risk (P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the candidate SNPs (P > 0.05). However, the fasting blood glucose (FBG) levels of rs6777038 CT carriers were significantly lower than TT carriers (4.69±0.69 vs. 5.03±1.57 mmol/L, P < 0.01), and the OGTT-2h levels of rs6777038 CC and CT genotype carriers were significantly lower than TT genotype carriers (8.10±1.91 and 8.08±1.87 vs. 8.99±2.90 mmol/L, P < 0.01). Conclusions: IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs11705701, rs6777038, rs16860234, rs7651090 polymorphisms were not significantly associated with GDM risk in Wuhan, China. Further lager multicenter researches are needed to confirm these results. [ABSTRACT FROM AUTHOR]

As one of the key materials used in the civil engineering industry, concrete has a global annual consumption of approximately 10 billion tons. Cement and fine aggregate are the main raw materials of concrete, and their production causes certain harm to the environment. As one of the countries with the largest production of industrial solid waste, China needs to handle solid waste properly. Researchers have proposed to use them as raw materials for concrete. In this paper, the effects of different lithium slag (LS) contents (0%, 10%, 20%, 40%) and different substitution rates of recycled fine aggregates (RFA) (0%, 10%, 20%, 30%) on the axial compressive strength and stress-strain curve of concrete are discussed. The results show that the axial compressive strength, elastic modulus, and peak strain of concrete can increase first and then decrease when LS is added, and the optimal is reached when the LS content is 20%. With the increase of the substitution rate of RFA, the axial compressive strength and elastic modulus of concrete decrease, but the peak strain increases. The appropriate amount of LS can make up for the mechanical defects caused by the addition of RFA to concrete. Based on the test data, the stress-strain curve relationship of lithium slag recycled fine aggregate concrete is proposed, which has a high degree of agreement compared with the test results, which can provide a reference for practical engineering applications. In this study, LS and RFA are innovatively applied to concrete, which provides a new way for the harmless utilization of solid waste and is of great significance for the control of environmental pollution and resource reuse. [ABSTRACT FROM AUTHOR]

In this paper, a daily gridded observation data across China from 1961 to 2022 were used to calculate daily potential evapotranspiration (PET). The observed variables included daily temperature, sunshine hours, average wind speed, and average relative humidity. PET was determined using the Penman-Monteith method recommended by the Food and Agriculture Organization (FAO). The long-term trend of PET was investigated in six regions of China during different seasons. To further compressed the influence of various meteorological factors on the PET trend, the contribution of each meteorological element to the long-term trend of PET was analyzed. The results indicate the following: (1) PET reaches its peak during summer which values from 145 to 640 mm, while it is lowest during winter from 21 to 244 mm. (2) The spatial patterns of PET trend changes are relatively similar across the four seasons, characterized by a decrease in the eastern regions and an increase in the western regions. The reduction is most significant during the summer and the range of trend is from -2.04 to 1.48 mm/day, while the increase becomes more pronounced in the winter which trend is from -0.34 to 0.53 mm/day. (3) The contribution of factors varies significantly across different regions. In spring and autumn, RH and U have little difference in contribution from other factors. But tsun is varies different from regions, the contribution value is largest in the northwest and smallest in the northeast. However, during summer, tsun become the most significant contributor in the YZ and SE regions, while in winter, Tm emerges as the most significant contributor to the PET trend in all six subregions. In SW, the contribution from U2 is the smallest in all seasons, with RH and Tm being the two crucial factors determining the PET trend in this region. [ABSTRACT FROM AUTHOR]

Skillful utilization of mental arithmetic can significantly improve students' mathematical computation ability. However, it was observed that primary school students often resort to reiterating the process of written arithmetic in their minds during mental arithmetic, which is not conducive to their numerical ability improvement. This paper devises a set of graphic teaching aids for primary school students' mental arithmetic improvement based on mental arithmetic strategies, schema theory, and working memory. To validate the effectiveness of schema teaching in enhancing mental arithmetic ability among primary school students, a controlled experiment was conducted with two groups of third-grade students randomly selected from a primary school in Jingshan City. The results, obtained through descriptive statistical analysis and the multitrait—multimethod approach (MTMM), indicated that the experimental group (n = 52) demonstrated significant improvements in speed, accuracy, and stability in mental addition and subtraction after a 14-day instruction period in schema teaching. This study offers a potent mental arithmetic teaching strategy for elementary mathematics education, which can lead to a comprehensive enhancement of students' mental calculation abilities. It also holds promise for inspiring innovative teaching methodologies in primary and secondary mathematics education in the future. [ABSTRACT FROM AUTHOR]

Background: The purpose of this paper is to explore the relationship between subjective well-being, social class identity, and Self-rated health among older persons,. Focusing on the mediating role of health and the impact of epidemic infectious diseases on these relationships. Methods: Based on the 2018 and 2021 China General Social Survey (CGSS) databases, the data were screened, and processed. Using Stata17, we employed ordered probit regression to examine the relationships among variables and Bootstrap methods to assess mediation effects, and the CGSS data for 2018 and 2021 were compared and analyzed. Results: Our results revealed that factors such as social class identity, health status, and personal income significantly positively impact older persons' subjective well-being (P<0.01). Notably, there was a partial mediating effect of health status between the subjective well-being of the elderly and social class identity. And findings showed that when older adults were affected by epidemic diseases, their subjective well-being, social class identity, and Self-rated health remained significantly positively correlated. Subjective well-being, social class identity. What is more noteworthy is that when affected by epidemic infectious diseases, older adults' subjective well-being, social class identity, and Self-rated health remained significantly positively correlated. The mediating role of self-rated health in older adults' subjective well-being and social class identity increased from 9.6% to 12.4%. Conclusions: In the face of epidemic infectious diseases, we need to pay more attention to the Self-rated health of the elderly, and the Chinese government should take effective measures to improve their health level, which will in turn improve the subjective well-being of the elderly and realize the goal of healthy aging. [ABSTRACT FROM AUTHOR]

Background: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. Materials and methods: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. Results: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745–0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0–A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B–D (p = 0.973); or who underwent non-curative treatments (p = 0.1). Conclusion: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies. [ABSTRACT FROM AUTHOR]

Background Previous studies have revealed the involvement of coffee and tea in the development of stroke and dementia. However, little is known about the association between the combination of coffee and tea and the risk of stroke, dementia, and poststroke dementia. Therefore, we aimed to investigate the associations of coffee and tea separately and in combination with the risk of developing stroke and dementia. Methods and findings This prospective cohort study included 365,682 participants (50 to 74 years old) from the UK Biobank. Participants joined the study from 2006 to 2010 and were followed up until 2020. We used Cox proportional hazards models to estimate the associations between coffee/tea consumption and incident stroke and dementia, adjusting for sex, age, ethnicity, qualification, income, body mass index (BMI), physical activity, alcohol status, smoking status, diet pattern, consumption of sugar-sweetened beverages, high-density lipoprotein (HDL), low-density lipoprotein (LDL), history of cancer, history of diabetes, history of cardiovascular arterial disease (CAD), and hypertension. Coffee and tea consumption was assessed at baseline. During a median follow-up of 11.4 years for new onset disease, 5,079 participants developed dementia, and 10,053 participants developed stroke. The associations of coffee and tea with stroke and dementia were nonlinear (P for nonlinear Conclusions We found that drinking coffee and tea separately or in combination were associated with lower risk of stroke and dementia. Intake of coffee alone or in combination with tea was associated with lower risk of poststroke dementia., Author(s): Yuan Zhang 1, Hongxi Yang 1,2, Shu Li 1, Wei-dong Li 3, Yaogang Wang 1,* Introduction Dementia is characterized by a progressive and unrelenting deterioration of mental capacity that [...]

Background: Echinolaelaps fukienensis is the dominant mite species parasitic on the body surface of the genus Niviventer. The mitochondrial genome (mitogenome) has its own independent genetic material and genetic system, and is now widely used in population genetics, genealogical biogeography, phylogeny and molecular evolution studies. Species diversity of the superfamily Dermanyssoidea is very rich, but its mitogenomes AT content is high, and it is difficult to amplify the complete mitogenome by routine PCR. To date, we have only obtained the mitogenomes of 6 species, scarcity on sequence data has greatly impeded the studies in the superfamily Dermanyssoidea. Methods: Echinolaelaps fukienensis were collected in 2019 from the body surface of Niviventer confucianus (Rodentia, Muridae) in Yunnan Province. The E. fukienensis mitogenome was determined and analyzed for the first time using the Illumina Novoseq 6000 platform. Phylogenetic analyses of the superfamily Dermanyssoidea were conducted based on the entire mitogenome sequences. Results: The E. fukienensis mitogenome was 14,402 bp, which is known the smallest genome of the superfamily Dermanyssoidea, encoding a total of 37 genes, including 13 PCGs, 22 tRNAs, 2 rRNAs and 1 control region. Most protein-coding genes use ATN as the start codon and TAN as the stop codon. AT and GC skew of atp8 genes in E. fukienensis were both 0. The average length of 22 tRNA genes of E. fukienensis was 64 bp, and secondary structures of tRNAs showed base mismatches and missing D-arms in many places. Compared with gene arrangement pattern of the hypothetical ancestor of arthropods, the E. fukienensis mitogenome shows a novel arrangement pattern. Phylogenetic tree supported the monophyly of the superfamily Dermanyssoidea. Echinolaelaps fukienensis being the least genetic distant (0.2762) and most closely related to Varroa destructor. Conclusions: This study analyzed comprehensive the structure and evolution of the E. fukienensis mitogenome for the first time, enriches molecular data of the genus Echinolaelaps, which will contribute to further understand phylogeny and rearrangement patterns of the superfamily Dermanyssoidea. [ABSTRACT FROM AUTHOR]

Background: Individuals with chronic low back pain (CLBP) exhibit altered brain function and trunk muscle activation. Aim: This study examined the effects of sling exercises on pain, function, and corticomuscular coherence (CMC) in healthy adults and individuals with CLBP. Methods: Eight individuals with CLBP and 15 healthy adults received sling exercise training for 6 weeks. Before and after training, participants performed two motor tasks: rapid arm lifts and repeated trunk flexion–extension tasks, and electromyography of the trunk muscles and electroencephalography of the sensorimotor cortex were recorded. Chi-squared test and Mann–Whitney U tests were used for between group comparison, and Wilcoxon signed-rank tests were used for pre- and post-training comparison. Spearman's Rank Correlation Coefficient (Rs) was used to identify for the relationship between motor performance and Corticomuscular coherence. Results: Sling exercises significantly improved pain (median from 3 to 1, p =.01) and Oswestry Disability Index scores (median from 2.5 to 2, p =.03) in the CLBP group. During rapid arm lifts, individuals with CLBP showed lower beta CMC of the transverse abdominis and internal oblique (Tra/IO) (0.8 vs. 0.49, p =.01) and lumbar erector spinae (0.70 vs. 0.38, p =.04) than the control group at baseline. During trunk flexion–extension, the CLBP group showed higher gamma CMC of the left Tra/IO than the control group at baseline (0.28 vs. 0.16 , p =.001). After training, all CMC became statistically non-significant between groups. The training induced improvement in anticipatory activation of the Tra/IO was positively correlated with the beta CMC (rs = 0.7851, p =.02). Conclusion: A 6-week sling exercises diminished pain and disability in patients with CLBP and improved the anticipatory activation and CMC in some trunk muscles. These improvements were associated with training induced changes in corticomuscular connectivity in individuals with CLBP. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis is a significant risk factor affecting patients' prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to develop a model with tumor necrosis as a variable to predict early tumor recurrence in HCC patients undergoing LR. Materials and methods: Patients who underwent LR between 2010 and 2018 for newly diagnosed HCC but did not receive neoadjuvant therapy were enrolled in this retrospective study. Six predictive factors based on pathological features—tumor size > 5 cm, multiple tumors, high-grade tumor differentiation, tumor necrosis, microvascular invasion, and cirrhosis—were chosen a priori based on clinical relevance to construct a multivariate logistic regression model. The variables were always retained in the model. The impact of each variable on early tumor recurrence within one year of LR was estimated and visualized using a nomogram. The nomogram's performance was evaluated using calibration plots with bootstrapping. Results: Early tumor recurrence was observed in 161 (21.3%) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence. Conclusion: We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory. [ABSTRACT FROM AUTHOR]

Viral infection triggers the activation of transcription factor IRF3, and its activity is precisely regulated for robust antiviral immune response and effective pathogen clearance. However, how full activation of IRF3 is achieved has not been well defined. Herein, we identified BLK as a key kinase that positively modulates IRF3-dependent signaling cascades and executes a pre-eminent antiviral effect. BLK deficiency attenuates RNA or DNA virus-induced ISRE activation, interferon production and the cellular antiviral response in human and murine cells, whereas overexpression of BLK has the opposite effects. BLK-deficient mice exhibit lower serum cytokine levels and higher lethality after VSV infection. Moreover, BLK deficiency impairs the secretion of downstream antiviral cytokines and promotes Senecavirus A (SVA) proliferation, thereby supporting SVA-induced oncolysis in an in vivo xenograft tumor model. Mechanistically, viral infection triggers BLK autophosphorylation at tyrosine 309. Subsequently, activated BLK directly binds and phosphorylates IRF3 at tyrosine 107, which further promotes TBK1-induced IRF3 S386 and S396 phosphorylation, facilitating sufficient IRF3 activation and downstream antiviral response. Collectively, our findings suggest that targeting BLK enhances viral clearance via specifically regulating IRF3 phosphorylation by a previously undefined mechanism. Author summary: Transcription factor IRF3-mediated type I interferon production is essential for antiviral innate immunity. Understanding how full activation of IRF3 is regulated is important to decipher the detailed mechanisms of IRF3-dependent signal transduction. Here, we report that BLK promotes IRF3 activation, leading to elevated antiviral cytokine production against multiple invading viruses both in vivo and in vitro. Upon viral infection, BLK undergoes Y309 autophosphorylation and directly phosphorylates IRF3 at Y107, together with TBK1-induced IRF3 S386 and S396 phosphorylation, to achieve sufficient IRF3 activation and elicit robust downstream antiviral responses. Overall, these data suggest that BLK is a critical effector of IRF3 phosphorylation. This study advances the understanding of the precise regulatory mechanisms of IRF3 activation. Manipulation of these mechanisms may help to develop novel therapeutics for infectious and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis and osteoarthritis are closely related. However, no high-quality studies have investigated the potential of micro-fragmented adipose tissue to treat patients with atherosclerosis accompanied by osteoarthritis. Methods: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, WANFANG DATA, and CQVIP were searched for potentially eligible studies published before October 13, 2022. Due to the statistical limitations of the existing relevant literature, it is not possible to make direct statistics on the patients with osteoarthritis accompanied by atherosclerosis treated by micro-fragmented adipose tissue. The primary outcome consisted of two parts: 1) Correlation between atherosclerosis and osteoarthritis; 2) Scores of the Knee injury and Osteoarthritis Outcome Score (KOOS). And secondary outcomes were pain assessed by visual analog scale (VAS) or numeric rating scale (NRS), quality of life (QoL) (assessed using tools apart from the KOOS), and adverse events (AEs). Random meta-analysis was conducted using STATA 14.0. Results: Nineteen studies were included. The metaanalysis evidenced a positive association between atherosclerosis and osteoarthritis (OR 1.17, CI 1.01–1.36). The mean absolute difference in KOOS subscale scores between pre- and post-treatment (mean with 95% confidence interval [CI]) was 19.65 (13.66, 25.63), 14.20 (4.64, 23.76), 19.95 (13.02, 26.89), 25.23 (14.80, 35.66), and 26.01 (13.68, 38.35) for pain, symptoms, activities of daily living (ADL), sports/recreation, and quality-of-life (QOL), respectively. The mean differences in VAS, resting VAS, activity VAS, and NRS between pre- and post-treatment was -8.24 (-10.66, —5.82), -3.61 (-4.49, -2.72), -4.17 (-4.89, -3.44), and -2.17 (-4.06, and -0.28), respectively. The mean difference in score of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EQ-5D, and University of California in Los Angeles (UCLA) between pre- and post-treatment was -24.81 (-40.80, -8.82), 0.07 (0.02, 0.12), and 0.30 (-0.42, 1.02), respectively. The mean difference in Tegner score and the International Knee Documentation Committee (IKDC) score between pre- and post-treatment was 0.67 (-0.62, 1.97) and 13.70 (6.35, 21.04), respectively. The use of micro-fragmented adipose tissue was associated with risk of bruising, bleeding, hematoma, drainage, infection, soreness, swelling, pain, and stiffness in harvest and injection sites. Conclusion: Atherosclerosis and osteoarthritis share common risk factors and comorbidity. And the use of micro-fragmented adipose tissue may benefit for improving symptoms of knee osteoarthritis accompanied by atherosclerosis although may lead to some mild adverse events. Randomized controlled trials with long-term follow-up are necessary for further evaluation because many limitations of this meta-analysis cannot be ignored. [ABSTRACT FROM AUTHOR]

Against the backdrop of the COVID-19 pandemic and China's pursuit of the "double circulation" strategy, scholars are increasingly focusing on ensuring high-quality economic development in China. In this regard, digital inclusive finance and consumer consumption are of utmost significance. This study employs panel data from 30 provinces and cities spanning 2011 to 2020 to explore the impact of digitized inclusive finance on consumer consumption and high-quality economic development through a spatial econometric model. Our findings indicate that integrating digital finance with consumer consumption and economic development fosters high-quality economic growth. Furthermore, our semi-parametric spatial lag model suggests a nonlinear relationship between digital inclusive finance and high-quality economic growth, shaped like an inverted "U". Additionally, we examine the mediating effect of consumer consumption on the relationship between digital inclusive finance and high-quality economic development. Our results reveal a substitution effect between digital inclusive financing and consumer consumption in promoting high-quality economic development. Therefore, it is essential to promote the development of digital inclusive finance, harness its positive spillover effects between regions, and encourage an increase in consumer consumption to optimize the consumption structure, upgrade and adjust the industrial structure, and spur growth in emerging industries. [ABSTRACT FROM AUTHOR]

This study explored how the holiday effect impacts the fluctuations in various scale indexes. Using differential and double-difference methods, the researchers of this study analyzed the impact of the lockdown in Wuhan, China on the holiday effect during the COVID-19 pandemic. The research objects used in this study include CSI All Share, CNI1000, CNI 2000, CNI Large Cap., CNI Mid-Cap., and CNI Small Cap. This study found that on behalf of the Chinese market index and the large, medium, and small-scale index, stock volatility is evident on the next day following successive holidays. Meanwhile, greater volatility is observed in small stocks' 4-day vacation (May 1, 11) than in a two-day vacation. The researchers discovered that the sealing effect causes investors to feel uncertain about the increased stock volatility. In terms of size, the net impact of the pandemic on the stock holiday effect is also greater for small stocks than for large stocks. This study's main contribution is the GARCH+DID hybrid method. [ABSTRACT FROM AUTHOR]

Objective: The effectiveness of sugemalimab vs. placebo in post-chemoradiotherapy patients with locally advanced, unresectable stage III NSCLC has been demonstrated and approved by China National Medical Products Administration. The purpose of this study was to assess the cost-effectiveness of sugemalimab vs. placebo for consolidation treatment of stage III NSCLC from the perspective of the Chinese healthcare system. Methods: A 3-state Markov model with a 3-week cycle length was performed to appraise the incremental cost-utility ratio (ICUR) of sugemalimab consolidation therapy based on the GEMSTONE-301 clinical trial over a 10-year time horizon. Only direct medical costs, including costs of drug (maintenance and subsequent treatment), routine follow-up, best supportive care, and terminal care in end of life were considered in this model. Costs and health utilities were obtained from local databases and published articles. Sensitivity and scenario analyses were adopted to evaluate the model uncertainty. Internal and external data sources were used to justify the plausibility of the extrapolated portion of the survival model chosen. Results: In comparison with the placebo, sugemalimab consolidation therapy was not cost-effective as it yielded an ICUR value of $90,277 and $49,692 for the concurrent chemoradiotherapy (cCRT) and the sequential chemoradiotherapy (sCRT) population at the willingness-to-pay (WTP) threshold of $37,663/QALYs, respectively. When taking the sugemalimab patient assistance program (PAP) into consideration, sugemalimab consolidation therapy was cost-effective with an ICUR dramatic decreases below the WTP. Sensitivity analyses demonstrated that the ICUR was most sensitive to the discount rate and subsequent treatment. However, none of the sensitive parameters could affect the cost-effective conclusions without or with PAP. Scenario analyses revealed that the model was particularly affected by assumptions regarding discount in sugemalimab, time horizon, mean duration of sugemalimab maintenance treatment. Conclusions: From the perspective of Chinese healthcare system, sugemalimab consolidation therapy was not a cost-effective strategy in cCRT and sCRT patients with unresectable stage III NSCLC. Given that the sugemalimab PAP was available, sugemalimab consolidation therapy became a cost-effective option. [ABSTRACT FROM AUTHOR]

Background: Amiodarone is commonly used during therapeutic hypothermia (TH) following cardiac arrest due to ventricular arrhythmias. However, electrophysiological changes and proarrhythmic risk after amiodarone treatment have not yet been explored in TH. Methods: Epicardial high-density bi-ventricular mapping was performed in pigs under baseline temperature (BT), TH (32–34°C), and amiodarone treatment during TH. The total activation time (TAT), conduction velocity (CV), local electrogram (LE) duration, and wavefront propagation from pre-specified segments were analyzed during sinus rhythm (SR) or right ventricular (RV) pacing (RVP), along with tissue expression of connexin 43. The vulnerability to ventricular arrhythmias was assessed. Results: Compared to BT, TH increased the global TAT, decreased the CV, and generated heterogeneous electrical substrate during SR and RVP. During TH, the CV reduction and LE duration prolongation were greater in the anterior mid RV than in the other areas, which changed the wavefront propagation in all animals. Compared to TH alone, amiodarone treatment during TH further increased the TAT and LE duration and decreased the CV. Heterogeneous conduction was partially attenuated after amiodarone treatment. After TH and amiodarone treatment, the connexin 43 expression in the anterior mid RV was lower than that in the other areas, compatible with the heterogeneous CV reduction. The animals under TH and amiodarone treatment had a higher incidence of inducible ventricular arrhythmias than those under BT or TH without amiodarone. Conclusion: Electrical heterogeneity during amiodarone treatment and TH was associated with vulnerability to ventricular arrhythmias. [ABSTRACT FROM AUTHOR]

The use of alcohol-based sanitizers has been recommended as an effective alternative to clean hands, especially in the case when hand washing is not doable. This is especially critical with the COVID-19 pandemic, where personal hygiene is an important factor to deter the spread of the virus. This study assesses and evaluates the differences in antibacterial efficacy and functionalities of five different commercial alcohol-based sanitizers with different formulations. All sanitizers were able to provide instant sanitization functionality, effectively killing 5x105 CFU/mL of inoculated bacteria. However, comparing pure alcohol-based sanitizers against alcohol-based sanitizers with a secondary active ingredient demonstrated that the addition of a secondary active ingredient enhanced the effectiveness and functionalities of the sanitizers. Alcohol-based sanitizers with secondary active ingredients demonstrated a more rapid antimicrobial mode of action, eradicating all 106 CFU/mL of bacteria within 15 seconds of contact, in contrast to the 30 min for purely alcohol-based sanitizers. The secondary active ingredient also provided additional anti-biofilm functionality to prevent opportunistic microbes from attaching and proliferating on the treated surface, leading to serious biofilm formation. On top of that, treatment of surfaces with alcohol-based sanitizers with secondary active ingredients also imparted prolonged antimicrobial protection to the surface lasting up to 24 h. On the other hand, purely alcohol-based sanitizers do not seem to possess such quality with the treated surface being vulnerable to microbial contamination within minutes after application. These results highlighted the benefits of adding a secondary active ingredient in sanitizer formulation. However, care needs to be taken to evaluate the type and concentration of antimicrobial agents chosen as the secondary active ingredient. [ABSTRACT FROM AUTHOR]

Background/objective: To determine the impact of microvascular invasion (MVI) on outcome in patients with solitary hepatocellular carcinoma (HCC) of ≤ 2 cm undergoing liver resection (LR). Methods: This retrospective study enrolled consecutive patients between 2007–2019 with newly diagnosed solitary HCC ≤ 2 cm who were undergoing LR at our institution. Overall survival (OS) and recurrent-free survival (RFS) were compared between patients with or without MVI. Results: Of the 229 patients included in this study, 71 had MVI. The median follow-up period was 28.8 months (interquartile range: 13.5–70.1). Although the 90-day mortality rate was 0, 18 deaths occurred during the study, and the 5-year survival rate was 87.1%. Tumor recurrence occurred in 45 cases, and 5-year RFS was 71.9%. The presence or absence of MVI did not significantly affect the OS and RFS rates (log rank test, p = 0.10 and 0.38, respectively). In univariate and multivariate analysis, the presence of MVI was not associated with OS and RFS. Conclusion: The presence of MVI was not associated with OS and RFS in patients with solitary HCC ≤ 2 cm who underwent LR in this cohort. [ABSTRACT FROM AUTHOR]

Ebola virus (EBOV) causes severe hemorrhagic fever in humans with high mortality. In Ebola virus disease (EVD) survivors, EBOV persistence in the eyes may break through the inner blood–retinal barrier (iBRB), leading to ocular complications and EVD recurrence. However, the mechanism by which EBOV affects the iBRB remains unclear. Here, we used the in vitro iBRB model to simulate EBOV in retinal tissue and found that Ebola virus-like particles (EBO-VLPs) could disrupt the iBRB. Cytokine screening revealed that EBO-VLPs stimulate pericytes to secrete vascular endothelial growth factor (VEGF) to cause iBRB breakdown. VEGF downregulates claudin-1 to disrupt the iBRB. Ebola glycoprotein is crucial for VEGF stimulation and iBRB breakdown. Furthermore, EBO-VLPs caused iBRB breakdown by stimulating VEGF in rats. This study provides a mechanistic insight into that EBOV disrupts the iBRB, which will assist in developing new strategies to treat EBOV persistence in EVD survivors. Author summary: Ebola virus (EBOV) persistence in eyes has been frequently reported and has become an enormous international public health challenge. EBOV persistence in the eyes may break through the inner blood–retinal–barrier (iBRB), leading to ocular complications and EBOV recurrence. However, the mechanism by which EBOV affects the iBRB remains unclear. Here, we found that Ebola virus-like particles stimulate retinal pericytes to secrete vascular endothelial growth factor (VEGF) to cause iBRB breakdown. VEGF causes iBRB breakdown by disrupting the tight junction protein claudin-1. Ebola glycoprotein plays a key role in VEGF stimulation and iBRB breakdown. Our study provides a mechanistic insight into that EBOV disrupts the iBRB, which will assist in developing new strategies to treat EBOV persistence in EBOV survivors. [ABSTRACT FROM AUTHOR]

In Fig 2, the control regions should have been one (CR) not two (CR1 and CR2). Please see the correct Fig 2 here.Graph: Fig 2 The complete mitogenome of Echinolaelaps fukienensis.Genes on the outside of the circle are coded on the major or J strand, whereas genes on the inside of the circle are on the complement (minor or N) strand.By Gangxian He; Wei Li; Bili Yuan and Wenge DongReported by Author; Author; Author; Author [Extracted from the article]

The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies. [ABSTRACT FROM AUTHOR]

The following information is missing from the Funding statement: This study was supported by the Cultivating Fund for National Natural Science Foundation of China of Shandong Provincial Qianfoshan Hospital (QYPY2019NSFC0603).By Chuanzhen Zhang; Wei Li; Xiyuan Li; Debin Wan; Savannah Mack; Jingjing Zhang; Karen Wagner; Chang Wang; Bowen Tan; Jason Chen; Ching-Wen Wu; Kaori Tsuji; Minoru Takeuchi; Ziping Chen; Bruce D. Hammock; Kent E. Pinkerton and Jun YangReported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

The construction of refuge spaces in rapidly urbanizing historic cities is a challenging task owing to their complex urban form, unique urban fabric, and historic preservation requirements. Refuge green space (RGS) is a green space that can serve as an emergency shelter in cities, providing a flexible means to increase the emergency shelter capacity for rapidly urbanized historic cities. After major earthquakes, spatial accessibility to GRSs is a critical planning strategy for disaster prevention and emergency response in historic cities. To match the RGS planning with the emergency service demand, we must examine the spatial disparity in access to existing RGSs. In this study, the urban area of Nanjing was selected as the target region to analyze the spatial disparity in access to RGSs using the Gaussian two-step floating catchment area method at four evacuation times (10, 20, 30, and 60 min). The results showed that the spatial accessibility exhibited clustering characteristics, where high-accessibility spaces were mainly distributed in the northern and southern regions of Nanjing. The increase in the evacuation time improved accessibility to RGSs, but the existing RGSs still could not sufficiently satisfy the emergency shelter needs of citizens. Based on the bivariate local Moran's I analysis of the RGS accessibility and population density, the spatial mismatch regions were dominant in the center of the urban area. These findings not only are expected to assist emergency planners by improving their strategic plans for emergency shelter investment in Nanjing and their ability to respond to catastrophic earthquakes, but also provide a strong reference for the construction of a safe environment in other rapidly developing historic cities that face earthquake threats. [ABSTRACT FROM AUTHOR]

Understanding the temporal and spatial distribution characteristics of the cultural heritage of the Yellow River Basin can effectively improve the scientific understanding of the historical changes, environmental evolution, and cultural and economic development of the Yellow River Basin and thus provide a scientific and reasonable decision-making basis for the protection and development of its cultural heritage. The research object of this paper are the national cultural relic protection units. These are examined using the GIS spatial analysis method to explore the spatial and temporal distribution characteristics and spatial structure of 2,102 national material cultural heritage sites in the Yellow River basin. The results show that the spatial distribution of cultural heritage has a significant spatial agglomeration effect. The whole basin is concentrated in stable high- and low-value areas, and the difference between the high- and low-value areas is clear. Some aspects of the spatial structure heterogeneity are strong, showing a low value dispersion distribution trend. In different periods, the distribution direction and scope of cultural heritage have low ranges of rotation, a clear direction, and a high degree of centripetal distribution. The spatial and temporal distribution of cultural heritage is the result of the combined action of natural geographical environment such as climate change, topography, river hydrology, and human environment such as administrative institutional changes, ideological evolution, and social and economic development. [ABSTRACT FROM AUTHOR]

Oncohistone mutations are crucial drivers for tumorigenesis, but how a living organism governs the loss-of-function oncohistone remains unclear. We generated a histone H2B triple knockout (3KO) strain in Caenorhabditis elegans, which decreased the embryonic H2B, disrupted cell divisions, and caused animal sterility. By performing genetic suppressor screens, we uncovered that mutations defective in the histone H3-H4 chaperone UNC-85 restored H2B 3KO fertility by decreasing chromatin H3-H4 levels. RNA interference of other H3-H4 chaperones or H3 or H4 histones also rescued H2B 3KO sterility. We showed that blocking H3-H4 chaperones recovered cell division in C. elegans carrying the oncohistone H2BE74K mutation that distorts the H2B-H4 interface and induces nucleosome instability. Our results indicate that reducing chromatin H3-H4 rescues the dysfunctional H2B in vivo and suggest that inhibiting H3-H4 chaperones may provide an effective therapeutic strategy for treating cancers resulting from loss-of-function H2B oncohistone. Author summary: Dysfunctional histones cause developmental defects and drive tumorigenesis. Using Caenorhabditis elegans to study histone H2B loss, we found that inhibiting histone H3-H4 chaperones restored fertility in H2B triple knockouts by decreasing chromatin H3-H4 levels. The blockade of H3-H4 chaperones recovered cell division in C. elegans carrying the oncohistone H2BE74K mutation that distorts the H2B-H4 interface and induces nucleosome instability. We suggest that the overall stoichiometry of histones within nucleosomes is more important than the actual abundances of histone dimers or tetramers and that inhibiting H3-H4 chaperones may provide an effective therapeutic strategy for treating cancers resulting from loss-of-function H2B oncohistone. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to examine the factors influencing China's new retail industry on corporate performance. We mainly design the adjustment effect of the internationalization of its new retail industry on corporate performance and proprietary assets. Design/Methodology/Approach: The framework is based on dynamic panel data of 590 listed companies in China's new retail industry from 2007 to 2019. Findings: We apply the concept of big data for the analysis and investigation, including the DOI explanatory variable for the degree of internationalization, Tobin's Q explained variable, and adjusted variable of proprietary assets (R&D intensity RDI, marketing intensity MI, and capital intensity CI). We found that the degree of internationalization of the new retail industry has a positive impact on corporate performance. Research limitations/implications: The resultant findings only reflect the setting of China's new retail marketplace. With the research model developed here in, future research can target cross-country studies of various forms of online and offline market sites to determine regional differences in the development of new retail activities. Originality/Value: The results show that the major new retail industry is a multi-channel concept that affects overall corporate performance. The authors focus on corporate performance, which is a moderating effect based on proprietary assets. [ABSTRACT FROM AUTHOR]

Giardia duodenalis, the causative agent of giardiasis, is among the most important causes of waterborne diarrheal diseases around the world. Giardia infection may persist over extended periods with intestinal inflammation, although minimal. Cyclooxygenase (COX)-2 is well known as an important inducer of inflammatory response, while the role it played in noninvasive Giardia infection remains elusive. Here we investigated the regulatory function of COX-2 in Giardia-induced pro-inflammatory response and defense-related nitric oxide (NO) generation in macrophage-like cell line, and identified the potential regulators. We initially found that Giardia challenge induced up-regulation of IL-1β, IL-6, TNF-α, prostaglandin (PG) E2, and COX-2 in macrophages, and pretreatment of the cells with COX-2 inhibitor NS398 reduced expressions of those pro-inflammatory factors. It was also observed that COX-2 inhibition could attenuate the up-regulated NO release and inducible NO synthase (iNOS) expression induced by Giardia. We further confirmed that Giardia-induced COX-2 up-regulation was mediated by the phosphorylation of p38 and ERK1/2 MAPKs and NF-κB. In addition, inhibition of reactive oxygen species (ROS) by NAC was shown to repress Giardia-induced activation of MAPK/NF-κB signaling, up-regulation of COX-2 and iNOS, increased levels of PGE2 and NO release, and up-expressions of IL-1β, IL-6, and TNF-α. Collectively, in this study, we revealed a critical role of COX-2 in modulating pro-inflammatory response and defense-related NO production in Giardia-macrophage interactions, and this process was evident to be controlled by ROS-dependent activation of MAPK/NF-κB signaling. The results can deepen our knowledge of anti-Giardia inflammatory response and host defense mechanisms. Author summary: During microbial infections, COX-2 has been well documented as a pro-inflammatory factor, while little is known about its regulatory function and mechanism. Here we described a novel role of COX-2 in regulating Giardia-induced pro-inflammatory response and defense-related NO enhancement, and this process was confirmed to be associated with ROS-dependent MAPK/NF-κB activation. The findings provide invaluable insights into the mechanisms underlying anti-Giardia host inflammatory responses, however, more research efforts should be directed to clarify why Giardia infection only induces mild inflammation in the small intestine of the host, so as to fully understand the pathogenesis of giardiasis. Anyway, in combination with the anti-apoptotic role of COX-2 in enterocytes during Giardia infection as noted recently, we could infer that COX-2 might have clinical implications for giardiasis treatment. [ABSTRACT FROM AUTHOR]

Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26–38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment. [ABSTRACT FROM AUTHOR]

Under the context of global warming, compound dry and hot events (CDHEs) will increase and bring serious losses to society and the economy. The projection of CDHEs is of great significance for policy-making and risk assessment. In this paper, two large ensemble simulations, CanESM2-LE and CESM-LE, are used to estimate the risk of extreme CDHEs under different warming scenarios in China. First, the biases of the model in the simulation of the temperature and precipitation over the China region are corrected, and the index of CDHEs is established based on a copula function. The results show that extreme CDHEs will occur more often in China with the increase in global warming and the more severe extreme CDHEs are, the greater the risk will be in the future with higher uncertainties. Events that would be attained once every 50 and 100 years in the current climate from CESM-LE (CAanESM2-LE) will be 1.2/1.6 (1.1/1.5) times and 1.3/2.3 (1.5/2.0) times more likely to occur in a 1.5°C/2.0°C warmer climate, respectively. Northwestern China will experience the greatest increase in the risk of extreme CDHEs. Extreme CDHEs expected once every 100 years in the current period over NW China are expected to occur approximately every 5 and 4 years under a 4.0°C warmer world in CanESM2-LE and CESM-LE, respectively. [ABSTRACT FROM AUTHOR]

The predictive value of non-invasive electrocardiographic examination findings for the risk of sudden cardiac death (SCD) in populations with structurally normal hearts remains unclear. This study aimed to investigate the characteristics of the QRS vectorcardiography of surface electrocardiography in patients with structurally normal hearts who experienced SCD. We consecutively enrolled patients who underwent vectorcardiography between March 2017 and December 2018 in a tertiary referral medical center. These patients didn't have structural heart diseases, histories of congestive heart failure, or reduced ejection fraction, and they were classified into SCD (with aborted SCD history and cerebral performance category score of 1) and control groups (with an intervention for atrioventricular node reentrant tachycardia and without SCD history). A total of 162 patients (mean age, 54.3±18.1 years; men, 75.9%), including 59 in the SCD group and 103 in the control group, underwent propensity analysis. The baseline demographic variables, underlying diseases, QRS loop descriptors (the percentage of the loop area, loop dispersion, and inter-lead QRS dispersion), and other electrocardiographic parameters were compared between the two groups. In the univariate and multivariate analyses, a smaller percentage of the loop area (odds ratio, 0.0003; 95% confidence interval, 0.00–0.02; p<0.001), more significant V4-5 dispersion (odds ratio, 1.04; 95% confidence interval, 1.02–1.07; p = 0.002), and longer QRS duration (odds ratio, 1.05; 95% confidence interval, 1.00–1.10; p = 0.04) were associated with SCD. In conclusion, the QRS loop descriptors of surface electrocardiography could be used as non-invasive markers to identify patients experiencing aborted SCD from a healthy population. A decreased percentage of loop area and elevated V4-5 QRS dispersion values assessed using vectorcardiography were associated with an increased risk of SCD in patients with structurally normal hearts. [ABSTRACT FROM AUTHOR]

A 65-day growth trial was conducted to investigate the dietary protein requirements for Culter mongolicus fingerlings. Isolipidic and isoenergetic diets were formulated with five dietary protein levels (32%, 37%, 42%, 47%, and 52%). Each diet was assigned to triplicate groups of 70 C. mongolicus fingerlings (0.99±0.08 g). The results indicated that weight gain and specific growth rate (SGR) increased with increasing dietary protein levels up to 47%. The activities of intestinal trypsin and lipase were the lowest in the 32% protein and 52% protein groups, while amylase activity reduced markedly in the 47% protein group. These results suggest that different dietary protein levels may cause different transformations of nutrients. The activities of superoxide dismutase (SOD) and lysozyme were not affected by varying dietary protein levels, except for those in the 32% protein group. In contrast, the content of malondialdehyde (MDA) increased with increasing dietary protein levels and reaching a maximum in the 52% protein group, suggesting that MDA accumulation depends on the protein concentration and the potential oxidative stress. Taken together, based on the broken-line analysis of SGR, we recommended the optimum dietary protein for C. mongolicus fingerlings to be 48.97%~49.31%. [ABSTRACT FROM AUTHOR]

Objective: To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. Methods: We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval. Results: Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80–1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66–0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57–0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events. Conclusion: Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases. [ABSTRACT FROM AUTHOR]

In boreal regions, the frequency of forest fires is increasing. In this study, thermogravimetric analysis was used to analyze the pyrolysis kinetics of dead surface combustibles in different forest types within the Daxing'an Mountains, China. The results show that the combustible material load of forest types, the Larix forest (LG) is relatively high. Base on the E of kinetic parameters, the LG, and Quercus forest (QM) forest types had relatively high combustibility values and comprehensive combustibility values for 1-, 10-, and 100-h time lags. According to the obtained P values, the pyrolysis of dead surface fuels with 1-, 10-, and 100-h time lags is relatively difficult in the Larix / Betula mixed forest (L-B) and QM forest types. Therefore, mixed forests of the LG, L-B, and QM tree species can be established as fire-resistant forests to establish a fire barrier, reduce the combustibility of forest stands, and reduce the possibility of forest fires. [ABSTRACT FROM AUTHOR]

While metabolic syndrome (MetS) is associated with frailty, the correlation of serum lactate dehydrogenase (sLDH) and frailty with MetS remain uncertain. To investigate the relationship between sLDH and frail components in the US with MetS. A total of 4,066 participants aged 40–90 years were assessed from the database of the third National Health and Nutrition Examination Survey, 1988–1994. The participants were classified into MetS and non-MetS groups. Multivariate logistic regression analysis with four models were performed to assess the odds ratio (OR) of the divided tertiles of sLDH levels with frailty, and frail components including slow walking (SW), weakness, exhaustion, low physical activity (LPA), and low body weight (LBW). Higher sLDH levels were positively associated with frailty in the MetS group (p = 0.024) but not in non-MetS group (p = 0.102). After covariate adjustments, the OR of frailty in the upper two tertiles compared to the lowest tertile and revealed statistical significance (p < 0.05). Frail components of SW, weakness, exhaustion, and LPA were associated with higher sLDH (p < 0.05) except for LBW in MetS and non-MetS groups. The results demonstrated the strong association of higher sLDH levels and frailty among US individuals with MetS. [ABSTRACT FROM AUTHOR]

Benzophenone (BPs) and 4-Methylbenzylidene Camphor are used as ultraviolet (UV) filters to protect the skin and hair in personal care products. The discharging of the three chemicals may endanger the receiving water ecosystem. In the present study, the mutagenicity of BP-6, BP-8, and 4-Methylbenzylidene Camphor was tested using the Salmonella typhimurium reverse mutation test (Ames test) in the system with and without rat liver microsomal preparations (S9). Four S.typhimurium strains, TA97, TA98, TA100, and TA102 were employed in the Ames tests. The mutagenicity was detected from all three chemicals. The addition of S9 increased the mutation ratios of three chemicals to four strains, except BP-6 to TA100 strain and 4-MBC to TA97 and TA98 strain. In the mixed experiment, all positive effects were detected in the absence of S9. However, the results all became negative in the presence of S9. For the mixture of BP-6 and 4-MBC, positive results were detected on four tester strains except for the TA100 strain. For the mixture of BP-6, BP-8, and 4-MBC, positive results were detected on four strains. The mixture test results showed antagonism in mutagenicity for the mixture of BP-6 and 4-MBC to TA98 and TA100 strains and the mixture of BP-6, BP-8, and 4-MBC to TA100 and TA102 strains. [ABSTRACT FROM AUTHOR]

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM2.5) exposure and Alzheimer's disease (AD), the PM2.5-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM2.5 via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM2.5 for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM2.5 exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM2.5 induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM2.5 exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM2.5 subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM2.5 after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM2.5-mediated development of AD. [ABSTRACT FROM AUTHOR]

Background: While the use of combination antiretroviral therapy (cART) has conferred significant reduction in morbidity and mortality, there are growing concerns about the metabolic complications of antiretroviral regimens in HIV-infected patients. The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) among people living with HIV (PLHIV) in Singapore. Methods: We conducted a retrospective study using the clinical database maintained by the Clinical HIV Programme at the National Centre for Infectious Diseases, Singapore. Treatment-experienced PLHIV on follow-up during 2015–2017 were included. MetS was defined as having three or more of the following five abnormalities: hypertriglyceridemia, HDL hypocholesterolemia, hypertension, obesity, and diabetes. Results: A total of 2,231 PLHIV were included in this study. 93.9% were men, and the median age at latest follow-up was 48 years. The median duration of HIV infection and duration of exposure to cART was 6.8 years and 5.7 years, respectively. All had been exposed to nucleoside reverse transcriptase inhibitors (NRTIs) as the first line of treatment, 93.9% to non-NRTIs, 28.6% to protease inhibitors (PIs) and 12.8% to integrase strand transfer inhibitors. The most common metabolic abnormality among PLHIV was HDL hypocholesterolemia (60.2%) followed by hypertriglyceridemia (45.5%). Of all the 2,231 individuals, 68.8% had at least one component of MetS. The overall prevalence of MetS was 23.6% (95% confidence interval 21.9%–25.4%). Of the 526 with MetS, the most common combination was HDL hypocholesterolemia, hypertriglyceridemia and hypertension (51.0%), followed by HDL hypocholesterolemia, hypertriglyceridemia, hypertension and diabetes (25.1%). Compared with PLHIV without MetS, a significantly higher proportion of those with MetS were ever on protease inhibitors (33.5% vs. 27.1%). Conclusion: MetS is common in PLHIV. In view of the progressive aging of HIV-infected population and long-term use of cART, regular monitoring for metabolic abnormalities, surveillance of drug effects and behavioural interventions are needed to optimize management and prevention of metabolic disorders in PLHIV. [ABSTRACT FROM AUTHOR]

Sufficient samples of extreme precipitation events are needed in order to obtain reliable estimates of the probability of their occurrence. Here, we use a large ensemble simulation with 50 members from the Canadian Earth System Model (CanESM2) under the representative concentration pathway 8.5 (RCP8.5) scenario to give future projection of the intensity and frequency of extreme precipitation events under different warming levels relative to the current climate over China. A bias-correction method based on quantile mapping is first used to remove systematic biases in the ensemble. The return value and return period are obtained by fitting enough annual maximum precipitation samples with the generalized extreme value to represent the intensity and frequency of extreme events, respectively. The results show that the average intensity of extreme precipitation in China will increase by nearly 8% per 1°C of global warming, which closely follows the Clausius–Clapeyron relation. Rarer extreme events will experience greater changes in frequency, especially under higher warming. The nationally averaged extreme precipitation events, presently expected to occur every 50 years (100 years) under the current climate conditions, are expected to occur approximately every 41 years (82 years), 32 years (62 years), 22 years (42 years) and 15 years (29 years) under warming levels of 1.5, 2.0, 3.0 and 4.0°C, respectively. Northwestern China (NW), southwestern China (SW) and the Yangtze River valley (YZ) exhibit the greatest increase in probability ratio (PR) under future climate condition. The risk of extreme precipitation events, currently expected to occur once every 50 years, will be nearly 11 (21) times more likely to occur under a climate warming by 3.0°C (4.0°C). Limiting warming to 1.5°C will help avoid approximately 40%-50%, 70%-80% and over 90% of the increase in the risk of extreme events in almost all subregions if the global mean surface temperature (GMST) continues warming to 2.0°C, 3.0°C and 4.0°C, respectively. Our study provides a useful information for the understanding the impact of climate change on the future risk of extreme events over China. [ABSTRACT FROM AUTHOR]

The number of new cases of leprosy reported worldwide has remained essentially unchanged for the last decade despite continued global use of free multidrug therapy (MDT) provided to any diagnosed leprosy patient. In order to more effectively interrupt the chain of transmission, new strategies will be required to detect those with latent disease who contribute to furthering transmission. To improve the ability to diagnose leprosy earlier in asymptomatic infected individuals, we examined the combined use of two well-known biomarkers of M. leprae infection, namely the presence of M. leprae DNA by PCR from earlobe slit skin smears (SSS) and positive antibody titers to the M. leprae-specific antigen, Phenolic Glycolipid I (anti-PGL-I) from leprosy patients and household contacts living in seven hyperendemic cities in the northern state of Pará, Brazilian Amazon. Combining both tests increased sensitivity, specificity and accuracy over either test alone. A total of 466 individuals were evaluated, including 87 newly diagnosed leprosy patients, 52 post-treated patients, 296 household contacts and 31 healthy endemic controls. The highest frequency of double positives (PGL-I+/RLEP+) were detected in the new case group (40/87, 46%) with lower numbers for treated (12/52, 23.1%), household contacts (46/296, 15.5%) and healthy endemic controls (0/31, 0%). The frequencies in these groups were reversed for double negatives (PGL-I-/RLEP-) for new cases (6/87, 6.9%), treated leprosy cases (15/52, 28.8%) and the highest in household contacts (108/296, 36.5%) and healthy endemic controls (24/31, 77.4%). The data strongly suggest that household contacts that are double positive have latent disease, are likely contributing to shedding and transmission of disease to their close contacts and are at the highest risk of progressing to clinical disease. Proposed strategies to reduce leprosy transmission in highly endemic areas may include chemoprophylactic treatment of this group of individuals to stop the spread of bacilli to eventually lower new case detection rates in these areas. [ABSTRACT FROM AUTHOR]

The recently reported "UK variant" (B.1.1.7) of SARS-CoV-2 is thought to be more infectious than previously circulating strains as a result of several changes, including the N501Y mutation. We present a 2.9-Å resolution cryo-electron microscopy (cryo-EM) structure of the complex between the ACE2 receptor and N501Y spike protein ectodomains that shows Y501 inserted into a cavity at the binding interface near Y41 of ACE2. This additional interaction provides a structural explanation for the increased ACE2 affinity of the N501Y mutant, and likely contributes to its increased infectivity. However, this mutation does not result in large structural changes, enabling important neutralization epitopes to be retained in the spike receptor binding domain. We confirmed this through biophysical assays and by determining cryo-EM structures of spike protein ectodomains bound to 2 representative potent neutralizing antibody fragments. [ABSTRACT FROM AUTHOR]

Streptomycin is considered to be one of the effective antibiotics for the treatment of plague. In order to investigate the streptomycin resistance of Y. pestis in China, we evaluated streptomycin susceptibility of 536 Y. pestis strains in China in vitro using the minimal inhibitory concentration (MIC) and screened streptomycin resistance-associated genes (strA and strB) by PCR method. A clinical Y. pestis isolate (S19960127) exhibited high-level resistance to streptomycin (the MIC was 4,096 mg/L). The strain (biovar antiqua) was isolated from a pneumonic plague outbreak in 1996 in Tibet Autonomous Region, China, belonging to the Marmota himalayana Qinghai–Tibet Plateau plague focus. In contrast to previously reported streptomycin resistance mediated by conjugative plasmids, the genome sequencing and allelic replacement experiments demonstrated that an rpsL gene (ribosomal protein S12) mutation with substitution of amino-acid 43 (K43R) was responsible for the high-level resistance to streptomycin in strain S19960127, which is consistent with the mutation reported in some streptomycin-resistant Mycobacterium tuberculosis strains. Streptomycin is used as the first-line treatment against plague in many countries. The emergence of streptomycin resistance in Y. pestis represents a critical public health problem. So streptomycin susceptibility monitoring of Y. pestis isolates should not only include plasmid-mediated resistance but also include the ribosomal protein S12 gene (rpsL) mutation, especially when treatment failure is suspected due to antibiotic resistance. Author summary: The plague natural foci are widely distributed in the world, and correspondingly, the plague still poses a significant threat to human health in some countries with endemic plague foci. Streptomycin is used as the first-line treatment against plague in many countries for the antibiotic is considered to be one of the effective antibiotics, particularly for the treatment of pneumonic plague. The resistance to streptomycin had been reported in Y. pestis strains from Madagascar in previous studies. In this study, we reported the high-level resistance to streptomycin in a clinical isolate of Y. pestis from a pneumonic patient in Tibet Autonomous Region, China, and a novel mechanism of streptomycin resistance, i.e. mutation in the rpsL gene were identified. The knowledge acquired about streptomycin resistance in Y. pestis will remain of great practical value. For the emergence of resistance to streptomycin in Y. pestis would render the treatment failure, thus corresponding antibiotic monitoring should be routinely carried out in countries threatened by plague. In addition, based on our further understanding about streptomycin resistance of Y. pestis isolates, such monitoring should not only include plasmid-mediated resistance but also include the ribosomal protein S12 gene (rpsL) mutation in Y. pestis isolates. [ABSTRACT FROM AUTHOR]