SP1 transcriptionally activates HTR2B to aggravate traumatic spinal cord injury by shifting microglial M1/M2 polarization.

BACKGROUND: Spinal cord injury (SCI) can result in structural and functional damage to the spinal cord, which may lead to loss of limb movement and sensation, loss of bowel and bladder control, and other complications. Previous studies have revealed the critical influence of trans-acting transcription factor 1 (SP1) in neurological pathologies, however, its role and mechanism in SCI have not been fully studied. METHODS: The study was performed using mouse microglia BV2 stimulated using lipopolysaccharide (LPS) and male adult mice subjected to spinal hitting. Western blotting was performed to detect protein expression of SP1, 5-hydroxytryptamine (serotonin) receptor 2B (HTR2B), BCL2-associated x protein (Bax), B-cell lymphoma-2 (Bcl-2), inducible nitric oxide synthase (iNOS), clusters of differentiation 86 (CD86), Arginase 1 (Arg-1) and clusters of differentiation 206 (CD206). Cell viability and apoptosis were analyzed by MTT assay and TUNEL assay. mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-4 (IL-4) and tumor necrosis factor-ß (TNF-ß) were quantified by quantitative real-time polymerase chain reaction. The association of SP1 and HTR2B was identified by chromatin immunoprecipitation assay and dual-luciferase reporter assay. HE staining assay was performed to analyze the pathological conditions of spinal cord tissues. RESULTS: LPS treatment induced cell apoptosis and inhibited microglia polarization from M1 to M2 phenotype, accompanied by an increase of Bax protein expression and a decrease of Bcl-2 protein expression, however, these effects were relieved after SP1 silencing. Mechanism assays revealed that SP1 transcriptionally activated HTR2B in BV2 cells, and HTR2B knockdown rescued LPS-induced effects on BV2 cell apoptosis and microglial M1/M2 polarization. Moreover, SP1 absence inhibited BV2 cell apoptosis and promoted microglia polarization from M1 to M2 phenotype by decreasing HTR2B expression. SCI mouse model assay further showed that SP1 downregulation could attenuate spinal hitting-induced promoting effects on cell apoptosis of spinal cord tissues and microglial M1 polarization. CONCLUSION: SP1 transcriptionally activated HTR2B to aggravate traumatic SCI by shifting microglial M1/M2 polarization.

Oral delivery of Eimeria acervulina transfected sequentially with two copies of the VP2 gene induces immunity against infectious bursal disease virus in chickens.

Chicken coccidiosis caused by Eimeria spp. can occur on almost all poultry farms, causing huge economic losses to the industry. Genetically manipulated Eimeria parasites as a vaccine vector to deliver viral antigens have been reported. In our preliminary study, transgenic E. acervulina expressing a VP2 gene (Ea-VP2) of the infectious bursal disease virus (IBDV) demonstrated partial protection against IBDV infection. To enhance immune responses, we aimed to increase the VP2 gene copy number in transgenic E. acervulina. In this study, we used a novel plasmid vector carrying a VP2 gene fused with three flag tags and a red fluorescent reporter gene (mCherry). The vector was introduced into Ea-VP2 sporozoites through nucleofection, leading to the generation of Ea-2VP2. Subsequent analysis revealed a notable escalation in the fluorescent rate, increasing from 0.11 to 95.1% following four consecutive passages facilitated by fluorescent-activated cell sorting. Verification via PCR, Western blot, and immunofluorescence confirmed the successful construction of the Ea-2VP2 population. Despite lower fecundity compared to wild-type E. acervulina, Ea-2VP2 maintained immunogenicity. Our research effectively created a transgenic E. acervulina strain transfected sequentially with two copies of the VP2 gene from IBDV. This modification resulted in an increased humoral immune response after primary immunization in chickens. Additionally, it demonstrated a degree of protection within the bursa against IBDV infection. Future studies will focus on further enhancing immune response levels.

NKAIN1, as an oncogene, promotes the proliferation and metastasis of breast cancer, affecting its prognosis.

Na, K-ATPase interaction (NKAIN) is a transmembrane protein family, which can interact with Na, K-ATPase ß1 subunit. NKAIN1 plays an important role in alcohol-dependent diseases such as endometrial and prostate cancers. However, the relationship between NKAIN1 and human breast cancer has not been studied. Hence, this study aimed to explore the relationship between NKAIN1 expression and breast cancer. Data used in this study were mainly from the Cancer Genome Atlas, including differential expression analysis, Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, multiple Cox regression analysis, co-expression gene analysis, and gene set enrichment analysis. Analyses were performed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunohistochemistry on 46 collected samples. The knockdown or overexpression of NKAIN1 in vitro in MCF-7 and MDA-MB-231 cell lines altered the proliferation and migration abilities of tumor cells. In vivo experiments further confirmed that NKAIN1 knockdown effectively inhibited the proliferation and migration of cancer cells. Therefore, our study identified NKAIN1 as an oncogene that is highly expressed in breast cancer tissues. The findings highlight the potential of NKAIN1 as a molecular biomarker of breast cancer.

Contrastive Multiscale Transformer for Image Dehazing.

Images obtained in an unfavorable environment may be affected by haze or fog, leading to fuzzy image details, low contrast, and loss of important information. Recently, significant progress has been achieved in the realm of image dehazing, largely due to the adoption of deep learning techniques. Owing to the lack of modules specifically designed to learn the unique characteristics of haze, existing deep neural network-based methods are impractical for processing images containing haze. In addition, most networks primarily focus on learning clear image information while disregarding potential features in hazy images. To address these limitations, we propose an innovative method called contrastive multiscale transformer for image dehazing (CMT-Net). This method uses the multiscale transformer to enable the network to learn global hazy features at multiple scales. Furthermore, we introduce feature combination attention and a haze-aware module to enhance the network's ability to handle varying concentrations of haze by assigning more weight to regions containing haze. Finally, we design a multistage contrastive learning loss incorporating different positive and negative samples at various stages to guide the network's learning process to restore real and non-hazy images. The experimental findings demonstrate that CMT-Net provides exceptional performance on established datasets and exhibits superior visual outcomes.

Predominance of the Blastocystis subtype ST5 among free-living sympatric rodents within pig farms in China suggests a novel transmission route from farms.

Blastocystis is a parasitic protist that can infect humans and various domestic and wild animals. However, there is limited research on the prevalence of this parasite among rodents, particularly those living in pig farm settings. Therefore, to investigate the occurrence, molecular characterization, and zoonotic potential of Blastocystis among rodents within pig farm environments, we conducted an investigation of 227 rodents and shrews from 34 pig farms located in Henan, Shaanxi, and Shanxi provinces of China using nested PCR of the SSU rRNA gene of Blastocystis. The potential transmission and public health implications were also assessed from a One Health perspective. Blastocystis was detected in 86 (37.9%) fecal samples. The highest infection rate was observed among Ruttus norvegicus (73.7%, 42/58), followed by Ruttus tanezumi (30.1%, 41/136), and Mus musculus (12.0%, 3/25). However, it was not detected among individuals with Apodemus agrarius (n = 1) and Crocidura shantungensis (n = 7). Five known zoonotic Blastocystis subtypes (ST1-ST5) were identified, with ST4 (51.2%, 44/86) and ST5 (40.7%, 35/86) being the predominant ones, followed by ST1 (3.5%, 3/86), ST3 (3.5%, 3/86), and ST2 (1.2%, 1/86). ST4 was prevalent among R. norvegicus (83.3%, 35/42), while ST5 dominated R. tanezumi (70.7%, 29/41). Furthermore, ST5 exhibited the widest distribution at pig farm level, accounting for 65.0% (13/20) of Blastocystis-positive pig farms. This investigation presents the first documented Blastocystis infection in R. tanezumi and M. musculus, highlighting the predominant presence of the zoonotic ST5 subtype in rodents for the first time. The results demonstrate that sympatric rodents can serve as natural reservoirs for Blastocystis and play a role in its transmission. These findings provide information on the dynamics of rodent transmission and emphasize the potential public health threat posed by zoonotic Blastocystis subtypes spillover from pig farms.

Long-Term Coherent Integration Algorithm for High-Speed Target Detection.

Long-term coherent integration (CI) can effectively improve the radar detection capability for high-speed targets. However, the range walk (RW) effect caused by high-speed motion significantly degrades the detection performance. To improve detection performance, this study proposes an improved algorithm based on the modified Radon inverse Fourier transform (denoted as IMRIFT). The proposed algorithm uses parameter searching for velocity estimation, designs a compensation function based on the relationship between velocity and distance walk and Doppler ambiguity terms, and performs CI based on the compensated signal. IMRIFT can achieve RW correction, avoid the blind-speed sidelobe (BSSL) effect caused by velocity mismatch, and improve detection performance, while ensuring low computational complexity. In addition, considering the relationship between energy concentration regions and bandwidth in the 2D frequency domain, a fast method based on IMIRFT is proposed, which can balance computational cost and detection capacity. Finally, a series of comparative experiments are conducted to demonstrate the effectiveness of the proposed algorithm and the fast method.

Low-Threshold Anti-Stokes Raman Microlaser on Thin-Film Lithium Niobate Chip.

Raman microlasers form on-chip versatile light sources by optical pumping, enabling numerical applications ranging from telecommunications to biological detection. Stimulated Raman scattering (SRS) lasing has been demonstrated in optical microresonators, leveraging high Q factors and small mode volume to generate downconverted photons based on the interaction of light with the Stokes vibrational mode. Unlike redshifted SRS, stimulated anti-Stokes Raman scattering (SARS) further involves the interplay between the pump photon and the SRS photon to generate an upconverted photon, depending on a highly efficient SRS signal as an essential prerequisite. Therefore, achieving SARS in microresonators is challenging due to the low lasing efficiencies of integrated Raman lasers caused by intrinsically low Raman gain. In this work, high-Q whispering gallery microresonators were fabricated by femtosecond laser photolithography assisted chemo-mechanical etching on thin-film lithium niobate (TFLN), which is a strong Raman-gain photonic platform. The high Q factor reached 4.42 × 106, which dramatically increased the circulating light intensity within a small volume. And a strong Stokes vibrational frequency of 264 cm-1 of lithium niobate was selectively excited, leading to a highly efficient SRS lasing signal with a conversion efficiency of 40.6%. And the threshold for SRS was only 0.33 mW, which is about half the best record previously reported on a TFLN platform. The combination of high Q factors, a small cavity size of 120 µm, and the excitation of a strong Raman mode allowed the formation of SARS lasing with only a 0.46 mW pump threshold.

Rainstorm and strong wind weathers largely increase greenhouse gases flux in shallow ponds.

Shallow-water ponds represent the hotspots of greenhouse gas (GHG) emissions. Most current studies focus on the temporal dynamics for GHGs in water, with little consideration given to the effects of weather changes. In this study, we measured and compared the concentrations and fluxes of CO2, CH4, and N2O from a pond in Northeast China under different meteorological conditions. Results showed that the rates of CO2, CH4, and N2O emissions from pond into the atmosphere during strong winds were 85.85 ± 7.55 mmol m-2 d-1, 22.05 ± 6.80 mmol m-2 d-1, and 10.87 ± 0.72 µmol m-2 d-1, respectively, significantly higher than those measured during non-rain weather. Among which, over 88 % of CH4 emissions were contributed by ebullition. Meanwhile, the CO2 and N2O flux were also significantly higher during heavy rainfall, reaching 100.05 ± 19.76 mmol m-2 d-1 and 5.90 ± 1.03 µmol m-2 d-1, respectively. Strong winds and precipitation induced sediment disturbances, high gas transport coefficients, reduced photosynthesis and oxygen greatly promoted the GHGs escape evasion. Wind speed, air pressure, solar radiation, and dissolved oxygen in water were important influencing factors. Our results emphasize the importance of capturing short-term weather disturbance events, especially rainstorm and strong winds, to accurately assess the annual GHG budget from these shallow water ecosystems.

Decreased stress shielding with poly-ether-ether-ketone tibial implant for total knee arthroplasty - A preliminary study using finite element analysis.

In total knee arthroplasty (TKA), the mechanical mismatch between cobalt-chromium (CoCr) alloy tibial implant and bone has been implicated in stress shielding and subsequent implant failure and bone resorption. This study investigates the biomechanical advantages of poly-ether-ether-ketone (PEEK) tibial implant, which exhibit properties analogous to those of the surrounding bone. A finite element analysis (FEA) was employed to assess and compare the biomechanical performances of PEEK and CoCr tibial implants in patients with and without osteoporosis. Four FEA models were constructed with PEEK and CoCr alloy implants in normal and osteoporotic tibias. Based on previous literature and our clinical experience, stresses measurements were taken at 16 points on the tibial plateau and 8 points on the two surfaces which were 10 mm and 20 mm apart from the tibial plateau, with specific regions quantified for stress shielding. The results showed significant differences in stress distribution between PEEK and CoCr implants. The PEEK implants exhibited higher equivalent stresses on the tibial plateau in all models (normal bone: 0.22 ± 0.07 MPa vs. 0.13 ± 0.06 MPa, p < 0.01; osteoporotic bone: 0.39 ± 0.06 MPa vs. 0.17 ± 0.07 MPa, p < 0.01). In non-osteoporotic models, the mean equivalent stresses on proximal tibial surfaces were similarly elevated for PEEK implants (0.29 ± 0.13 MPa vs. 0.21 ± 0.08 MPa, p = 0.02). The CoCr implants demonstrated more stress shielding across all measured regions (tibial plateau: 23.47% vs. 2.73%; surface 1: 15.93% vs. 1.37%; surface 2: 10.71% vs. 6.56%). These disparities were even more pronounced in osteoporotic models in the CoCr group (tibial plateau: 32.50% vs. 8.36%). The maximum equivalent stresses on the tibial plateau further supported this trend (normal bone: 1.02 MPa vs. 0.52 MPa; osteoporotic bone: 1.43 MPa vs. 0.67 MPa). These data confirm the hypothesis that a PEEK tibial implant can reduce peri-prosthetic stress shielding, suggesting that PEEK implants have the capability to distribute loads more uniformly and maintain a closer approximation to physiological conditions.

Significant inter-annual fluctuation in CO2 and CH4 diffusive fluxes from subtropical aquaculture ponds: Implications for climate change and carbon emission evaluations.

Aquaculture ponds are potential hotspots for carbon cycling and emission of greenhouse gases (GHGs) like CO2 and CH4, but they are often poorly assessed in the global GHG budget. This study determined the temporal variations of CO2 and CH4 concentrations and diffusive fluxes and their environmental drivers in coastal aquaculture ponds in southeastern China over a five-year period (2017-2021). The findings indicated that CH4 flux from aquaculture ponds fluctuated markedly year-to-year, and CO2 flux varied between positive and negative between years. The coefficient of inter-annual variation of CO2 and CH4 diffusive fluxes was 168% and 127%, respectively, highlighting the importance of long-term observations to improve GHG assessment from aquaculture ponds. In addition to chlorophyll-a and dissolved oxygen as the common environmental drivers, CO2 was further regulated by total dissolved phosphorus and CH4 by dissolved organic carbon. Feed conversion ratio correlated positively with both CO2 and CH4 concentrations and fluxes, showing that unconsumed feeds fueled microbial GHG production. A linear regression based on binned (averaged) monthly CO2 diffusive flux data, calculated from CO2 concentrations, can be used to estimate CH4 diffusive flux with a fair degree of confidence (r2 = 0.66; p < 0.001). This algorithm provides a simple and practical way to assess the total carbon diffusive flux from aquaculture ponds. Overall, this study provides new insights into mitigating the carbon footprint of aquaculture production and assessing the impact of aquaculture ponds on the regional and global scales.

Self-Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors.

Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self-destructive and multienzymatically active copper-quinone-GOx nanoparticles (abbreviated as CQG NPs) have been designed to induce harmonious and balanced pyroptosis and cuproptosis using the "Tai Chi mindset" to awaken the immune response for suppressing dormant and recurrent tumors. This cleverly designed material can disrupt the antioxidant defense mechanism of tumor cells by inhibiting the nuclear factor-erythroid 2-related factor 2 (NRF2)-quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis. Meanwhile, cuproptosis can be triggered by copper ions released from the self-destructive disintegration of CQG NPs and the sensitivity of cancer cells to cuproptosis is enhanced through the depletion of endogenous copper chelators via the Michael addition reaction between glutathione (GSH) and quinone ligand, oxygen production from catalase-like reaction, and starvation-induced glucose deficiency. More importantly, CQG NPs-induced pyroptosis and cuproptosis can promote immunosuppressive tumor microenvironment (TME) remodeling, enhance the infiltration of immune cells into the tumor, and activate robust systemic immunity. Collectively, this study provides a new strategy to resist tumor dormancy, prevent tumor recurrence, and improve the clinical prognosis of tumors.

MiR-4521 affects the propagation of Cryptosporidium parvum in HCT-8 cells through targeting foxm1 by regulating cell apoptosis.

Cryptosporidium parvum could regulate the expression of microRNAs of epithelial cells to facilitate its intracellular propagation. MiR-4521 has been reported to play an important role during the development and progression of tumors and infectious diseases by regulating cell proliferation, apoptosis, and autophagy. However, the implication of miR-4521 during C. parvum infection was still unknown. In this study, the expression of miR-4521 was found to be upregulated in HCT-8 cells infected with C. parvum from 8 h post-infection (pi) to 48 hpi, and its upregulation would be related with the TLR/NF-κB signal pathway during C. parvum infection. One potential target of miR-4521, foxm1, was down-regulated in HCT-8 cells from 24 hpi to 48 hpi, and the expression of foxm1 was negatively regulated by miR-4521. The target relationship between miR-4521 and foxm1 was further validated by using dual luciferase reporter assay. Further studies showed that miR-4521 promoted the propagation of C. parvum in HCT-8 cells through targeting foxm1 by regulating BCL2-mediating cell apoptosis. These results contribute to further understanding of the regulatory mechanisms of host miRNAs during Cryptosporidium infection.

GREB1L overexpression is associated with good clinical outcomes in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor among women worldwide. GREB1L is a protein-coding gene. Previous studies have shown that GREB1L plays a vital role in lung and gastric adenocarcinoma. Currently, there is no relevant report about its role in breast cancer. METHODS: The Cancer Genome Atlas database was used to compare the expression level of GREB1L between tumor and normal tissues. The TISIDB website was used for prognosis analysis. The LinkedOmics database was used to predict the potential biological mechanism of GREB1L in breast cancer. Immunohistochemistry was used to detect the GREB1L expression level in breast tissue. Western blotting was used to detect the GREB1L expression level in cell lines. Transwell assays, CCK-8 cell proliferation assays, and colony formation assays were used to detect the migration, invasion, proliferation, and colony formation abilities of cells. Subcutaneous xenograft models were used to detect the in vivo tumor formation abilities of cells. RESULTS: GREB1L is highly expressed in breast cancer tissues and breast cancer cells. KEGG enrichment analysis suggested that GREB1L participates in the regulation of the Hedgehog signaling pathway; changes in GREB1L expression affected the migration and invasion abilities of MCF7 and MDA-MB-231 cells. Although changes in GREB1L expression did not affect their proliferation and colony formation abilities in vitro and in vivo, they affected the expression of tumor metastasis-related genes in vivo. The overexpression of GREB1L in breast cancer predicted a favorable prognosis. CONCLUSION: These results showed that GREB1L is involved in the development of breast cancer, and it may be a potential molecular marker for predicting the prognosis of breast cancer.

Transcription factors NF-YB involved in embryogenesis and hormones responses in Dimocarpus Longan Lour.

Introduction: NF-YB transcription factor is an important regulatory factor in plant embryonic development. Results: In this study, 15 longan NF-YB (DlNF-YB) family genes were systematically identified in the whole genome of longan, and a comprehensive bioinformatics analysis of DlNF-YB family was performed. Comparative transcriptome analysis of DlNF-YBs expression in different tissues, early somatic embryogenesis (SE), and under different light and temperature treatments revealed its specific expression profiles and potential biological functions in longan SE. The qRT-PCR results implied that the expression patterns of DlNF-YBs were different during SE and the zygotic embryo development of longan. Supplementary 2,4-D, NPA, and PP333 in longan EC notably inhibited the expression of DlNF-YBs; ABA, IAA, and GA3 suppressed the expressions of DlNF-YB6 and DlNF-YB9, but IAA and GA3 induced the other DlNF-YBs. Subcellular localization indicated that DlNF-YB6 and DlNF-YB9 were located in the nucleus. Furthermore, verification by the modified 5'RNA Ligase Mediated Rapid Amplification of cDNA Ends (5' RLM-RACE) method demonstrated that DlNF-YB6 was targeted by dlo-miR2118e, and dlo-miR2118e regulated longan somatic embryogenesis (SE) by targeting DlNF-YB6. Compared with CaMV35S- actuated GUS expression, DlNF-YB6 and DlNF-YB9 promoters significantly drove GUS expression. Meanwhile, promoter activities were induced to the highest by GA3 but suppressed by IAA. ABA induced the activities of the promoter of DlNF-YB9, whereas it inhibited the promoter of DlNF-YB6. Discussion: Hence, DlNF-YB might play a prominent role in longan somatic and zygotic embryo development, and it is involved in complex plant hormones signaling pathways.

Integrated transcriptomic and metabolomic analysis reveals the metabolic programming of GM-CSF- and M-CSF- differentiated mouse macrophages.

Macrophages play a critical role in the inflammatory response and tumor development. Macrophages are primarily divided into pro-inflammatory M1-like and anti-inflammatory M2-like macrophages based on their activation status and functions. In vitro macrophage models could be derived from mouse bone marrow cells stimulated with two types of differentiation factors: GM-CSF (GM-BMDMs) and M-CSF (M-BMDMs), to represent M1- and M2-like macrophages, respectively. Since macrophage differentiation requires coordinated metabolic reprogramming and transcriptional rewiring in order to fulfill their distinct roles, we combined both transcriptome and metabolome analysis, coupled with experimental validation, to gain insight into the metabolic status of GM- and M-BMDMs. The data revealed higher levels of the tricarboxylic acid cycle (TCA cycle), oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and urea and ornithine production from arginine in GM-BMDMs, and a preference for glycolysis, fatty acid storage, bile acid metabolism, and citrulline and nitric oxide (NO) production from arginine in M-BMDMs. Correlation analysis with the proteomic data showed high consistency in the mRNA and protein levels of metabolic genes. Similar results were also obtained when compared to RNA-seq data of human monocyte derived macrophages from the GEO database. Furthermore, canonical macrophage functions such as inflammatory response and phagocytosis were tightly associated with the representative metabolic pathways. In the current study, we identified the core metabolites, metabolic genes, and functional terms of the two distinct mouse macrophage populations. We also distinguished the metabolic influences of the differentiation factors GM-CSF and M-CSF, and wish to provide valuable information for in vitro macrophage studies.

Molecular Characterization of Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi and Escherichia coli in Dairy Goat Kids with Diarrhea in Partial Regions of Shaanxi Province, China.

Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi and Escherichia coli are important diarrheal pathogens threatening the health of humans and various animals. Goats, especially pre-weaned goat kids, that carry these pathogens are important reservoirs related to human infection. In the present study, PCR-based sequencing techniques were applied to characterize Cryptosporidium spp., G. duodenalis, E. bieneusi and E. coli in 202 fecal samples of diarrheal kids for Guanzhong dairy goats from five locations in Shaanxi Province. The positive rates of Cryptosporidium spp., G. duodenalis, E. bieneusi and E. coli were 37.6% (76/202), 16.3% (33/202), 55.4% (112/202) and 78.7% (159/202) in these goat kids, respectively. Co-infection of two to four pathogens was found in 114 of 202 fecal samples. Significant differences (p < 0.001) in the positive rates of Cryptosporidium spp. and G. duodenalis were found among locations and age groups. Furthermore, two Cryptosporidium species (C. parvum and C. xiaoi), two G. duodenalis assemblages (E and A), nine E. bieneusi genotypes (CHG3, CHG1, BEB6, CHG5, CHG2, SX1, CHG28, COS-II and CD6) and two E. coli pathotypes (EPEC and EHEC) were identified. As for Cryptosporidium, two (IIdA19G1 and IIdA19G2) and two (XXIIIa and XXIIIg) subtypes were recognized in samples positive for C. parvum and C. xiaoi, respectively. A phylogenetic analysis based on the ITS locus of E. bieneusi indicated that all nine genotypes of E. bieneusi identified in this study belonged to the group 2. Four virulence factors (ehxA, eae, stx2 and stx1) of EPEC and EHEC were found in E. coli strains. Collectively, this study explored the colonization frequency of Cryptosporidium spp., G. duodenalis, E. bieneusi and E. coli in diarrheal kids of Guanzhong dairy goats in Shaanxi Province and expanded our understanding of the genetic composition and zoonotic potential of these pathogens in goats.

High genotype diversity and zoonotic potential of Enterocytozoon bieneusi in yaks (Bos grunniens) from Ganzi Tibetan Autonomous Prefecture, Sichuan Province.

Enterocytozoon bieneusi is a common pathogen in humans and various animals, threatening the breeding industry and public health. However, there is limited information on the molecular characteristics of E. bieneusi in yaks, an economically important animal mainly domesticated in the Qinghai Tibet Plateau in China. In the present study, nested PCR targeting the ITS gene region was applied to investigate the positive rates and genetic diversity of E. bieneusi in 223 faecal samples of yaks from three locations in Ganzi Tibetan Autonomous Prefecture, Sichuan Province. The total positive rate of E. bieneusi was 23.8% (53/223). Significant differences in positive rates were identified among yaks from three locations (χ2 = 8.535, p = 0.014) and four age groups (χ2 = 17.259, p = 0.001), with the highest positive rates in yaks from Yajiang and aged < 6 months, respectively. Sequence analysis identified seven known (EbpC, LW1, LQ10, PigEBITS5, ESH-01, J and BEB4) and five novel (Ganzi1-5) ITS genotypes. Phylogenetic analysis showed eight genotypes (EbpC, LW1, LQ10, PigEBITS5, ESH-01, Ganzi1, Ganzi2 and Ganzi4) in group 1 and three genotypes (J, BEB4 and Ganzi3) in group 2, indicating high genotype diversity and zoonotic potential of E. bieneusi in yaks from Ganzi. Considering the increasing zoonotic genotypes in yaks in the present study compared with previous findings, interventions should be developed to reduce the potential transmission of E. bieneusi between humans and animals.

Title: Grande diversité génotypique et potentiel zoonotique d'Enterocytozoon bieneusi chez les yaks (Bos grunniens) de la préfecture autonome tibétaine de Ganzi, province du Sichuan. Abstract: Enterocytozoon bieneusi est un agent pathogène courant chez l'homme et chez divers animaux, menaçant l'industrie de l'élevage et la santé publique. Cependant, il existe peu d'informations sur les caractéristiques moléculaires d'E. bieneusi chez les yaks, un animal important pour l'économie, principalement domestiqué sur le plateau du Qinghai au Tibet en Chine. Dans la présente étude, une PCR imbriquée ciblant la région du gène ITS a été appliquée pour étudier la positivité et la diversité génétique d'E. bieneusi dans 223 échantillons fécaux de yaks provenant de trois sites de la préfecture autonome tibétaine de Ganzi, province du Sichuan. Le taux total de positivité pour E. bieneusi était de 23,8 % (53/223). Des différences significatives dans les taux positifs ont été identifiées parmi les yaks de trois emplacements (χ2 = 8,535, P = 0,014) et de quatre groupes d'âge (χ2 = 17,259, P = 0,001), avec les taux positifs les plus élevés respectivement chez les yaks de Yajiang et ceux âgés de moins de 6 mois. L'analyse de séquence a identifié sept génotypes ITS connus (EbpC, LW1, LQ10, PigEBITS5, ESH-01, J et BEB4) et cinq nouveaux (Ganzi1­5). L'analyse phylogénétique a montré huit génotypes (EbpC, LW1, LQ10, PigEBITS5, ESH-01, Ganzi1, Ganzi2 et Ganzi4) dans le groupe 1 et trois génotypes (J, BEB4 et Ganzi3) dans le groupe 2, indiquant une diversité génotypique élevée et un potentiel zoonotique d'E. bieneusi chez les yaks de Ganzi. Compte tenu de l'augmentation des génotypes zoonotiques chez les yaks dans la présente étude par rapport aux résultats précédents, des interventions devraient être développées pour réduire la transmission potentielle d'E. bieneusi entre les humains et les animaux.

Effect of lorecivivint on osteoarthritis: A systematic review and meta-analysis.

Objective: To comprehensively evaluate the effectiveness and safety of lorecivivint inhibitors in the treatment of osteoarthritis through meta-analysis. Methods: A comprehensive literature search on lorecivivint inhibitors in osteoarthritis was performed using electronic databases such as PubMed, Embase, Web of Science, and CochraneLibrary up to July 30, 2022. Two reviewers independently screened, evaluated, and reviewed the eligible studies. Data analysis and processing were carried out using RevMan 5.4 software. Results: A total of six studies involving 3056 participants were included. Meta-analysis showed that compared with the control group, lorecivivint significantly increased WOMAC discomfort (0.03 mg Week 12) (MD = -0.21, 95% CI [-1.94 - 1.53]; P = 0.81), WOMAC function (0.07 mg Week 24) (MD = -1.81, 95% CI [-4.74 - 1.12]; P = 0.23) and Joint space width (0.23 mg Week 24) (MD = -1.16, 95% CI [-3.69 - 1.38]; P = 0.37). Conclusion: A new treatment method combining Wnt pathway modulators with intra-articular CLK2/DYRK1A inhibitors could be a promising therapy for treating osteoarthritis. Lorecivivint was found to significantly improve WOMAC discomfort, WOMAC function, and joint space width in osteoarthritis patients. It is anticipated to be a reliable, safe, and effective treatment option for osteoarthritis with significant therapeutic utility and potential applications.

Consequences of using poly-ether-ether-ketone versus traditional implant on tibial cement penetration and short-term clinical outcomes during total knee arthroplasty: a randomized controlled trial.

BACKGROUND: The use of poly-ether-ether-ketone (PEEK) prosthesis during total knee arthroplasty (TKA) is a relatively new concept. Several studies have suggested that the thickness of cement penetration during TKA may affect the stability of the implants. The present study aimed to compare the cement penetration and clinical performance between PEEK and traditional cobalt chromium molybdenum (CoCrMo) prosthesis during TKA. METHODS: This study was a randomized controlled trial with level I of evidence. A total of 48 patients were randomly assigned to either the PEEK group (n = 24) or the CoCrMo group (n = 24). Mean bone cement penetration under the tibial baseplate was assessed radiographically in four zones in the anteroposterior view and two zones in the lateral view, in accordance with the Knee Society Scoring System. Furthermore, parameters such as the Knee Society Score (KSS), visual analogue scale (VAS) scores, complications and survivorship at 1 year postoperatively were also compared. RESULTS: According to the results of this study, the mean bone cement penetration exhibited no significant difference between PEEK and CoCrMo groups (2.49 ± 0.61 mm vs. 2.53 ± 0.68 mm, p = 0.85). Additionally, there were no remarkable differences in the KSS clinical score, functional score, and VAS score between the two groups. Moreover, complications and survivorship were also statistically compared between the groups and presented no significant differences. CONCLUSIONS: Based on the current findings, it can be concluded that PEEK implant present similar bone cement penetration, short-term clinical outcomes, and survivorship with traditional CoCrMo implant in TKA without added complications. Trial registration Chinese Clinical Trial Registry (ChiCTR2100047563).

Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA.

Introduction: The prognosis of bladder cancer (BLCA) and response to immune checkpoint inhibitors (ICIs) are determined by multiple factors. Existed biomarkers for predicting the effect of immunotherapy cannot accurately predict the response of BLCA patients to ICIs. Methods: To further accurately stratify patients' response to ICIs and identify potential novel predictive biomarkers, we used the known T cell exhaustion (TEX)-related specific pathways, including tumor necrosis factor (TNF), interleukin (IL)-2, interferon (IFN)-g, and T- cell cytotoxicpathways, combined with weighted correlation network analysis (WGCNA) to analyze the characteristics of TEX in BLCA in detail, constructed a TEX model. Results: This model including 28 genes can robustly predict the survival of BLCA and immunotherapeutic efficacy. This model could divide BLCA into two groups, TEXhigh and TEXlow, with significantly different prognoses, clinical features, and reactivity to ICIs. The critical characteristic genes, such as potential biomarkers Charged Multivesicular Body Protein 4C (CHMP4C), SH2 Domain Containing 2A (SH2D2A), Prickle Planar Cell Polarity Protein 3 (PRICKLE3) and Zinc Finger Protein 165 (ZNF165) were verified in BLCA clinical samples by real-time quantitative chain reaction (qPCR) and immunohistochemistry (IHC). Discussion: Our findings show that the TEX model can serve as biological markers for predicting the response to ICIs, and the involving molecules in the TEX model might provide new potential targets for immunotherapy in BLCA.