Nitric oxide-induced lipophagic defects contribute to testosterone deficiency in rats with spinal cord injury.

Introduction: Males with acute spinal cord injury (SCI) frequently exhibit testosterone deficiency and reproductive dysfunction. While such incidence rates are high in chronic patients, the underlying mechanisms remain elusive. Methods and results: Herein, we generated a rat SCI model, which recapitulated complications in human males, including low testosterone levels and spermatogenic disorders. Proteomics analyses showed that the differentially expressed proteins were mostly enriched in lipid metabolism and steroid metabolism and biosynthesis. In SCI rats, we observed that testicular nitric oxide (NO) levels were elevated and lipid droplet-autophagosome co-localization in testicular interstitial cells was decreased. We hypothesized that NO impaired lipophagy in Leydig cells (LCs) to disrupt testosterone biosynthesis and spermatogenesis. As postulated, exogenous NO donor (S-nitroso-N-acetylpenicillamine (SNAP)) treatment markedly raised NO levels and disturbed lipophagy via the AMPK/mTOR/ULK1 pathway, and ultimately impaired testosterone production in mouse LCs. However, such alterations were not fully observed when cells were treated with an endogenous NO donor (L-arginine), suggesting that mouse LCs were devoid of an endogenous NO-production system. Alternatively, activated (M1) macrophages were predominant NO sources, as inducible NO synthase inhibition attenuated lipophagic defects and testosterone insufficiency in LCs in a macrophage-LC co-culture system. In scavenging NO (2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO)) we effectively restored lipophagy and testosterone levels both in vitro and in vivo, and importantly, spermatogenesis in vivo. Autophagy activation by LYN-1604 also promoted lipid degradation and testosterone synthesis. Discussion: In summary, we showed that NO-disrupted-lipophagy caused testosterone deficiency following SCI, and NO clearance or autophagy activation could be effective in preventing reproductive dysfunction in males with SCI.

Biomarkers of preschool children with autism spectrum disorder: quantitative analysis of whole-brain tissue component volumes, intelligence scores, ADOS-CSS, and ages of first-word production and walking onset.

BACKGROUND: Preschooling is a critical time for intervention in children with autism spectrum disorder (ASD); thus, we analyzed brain tissue component volumes (BTCVs) and clinical indicators in preschool children with ASD to identify new biomarkers for early screening. METHODS: Eighty preschool children (3-6 years) with ASD were retrospectively included. The whole-brain myelin content (MyC), white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), and non-WM/GM/MyC/CSF brain component volumes were obtained using synthetic magnetic resonance imaging (SyMRI). Clinical data, such as intelligence scores, autism diagnostic observation schedule-calibrated severity scores, age at first production of single words (AFSW), age at first production of phrases (AFP), and age at walking onset (AWO), were also collected. The correlation between the BTCV and clinical data was evaluated, and the effect of BTCVs on clinical data was assessed by a regression model. RESULTS: WM and GM volumes were positively correlated with intelligence scores (both P < 0.001), but WM and GM did not affect intelligence scores (P = 0.116, P = 0.290). AWO was positively correlated with AFSW and AFP (both P < 0.001). The multivariate linear regression analysis revealed that MyC, AFSW, AFP, and AWO were significantly different (P = 0.005, P < 0.001, P < 0.001). CONCLUSIONS: This study revealed positive correlations between WM and GM volumes and intelligence scores. Whole-brain MyC affected AFSW, AFP, and AWO in preschool children with ASD. Noninvasive quantification of BTCVs via SyMRI revealed a new visualizable and quantifiable biomarker (abnormal MyC) for early ASD screening in preschool children.

Extended HPV typing test performed better predict value for CIN2+ among elderly women in China.

Objective: The aim of this study was to examine the cervical cancer screening practices among women residing in Lingang New District of Shanghai. Moreover, the study aimed to delve into the characteristics of HPV infection and cervical lesions in older women (≥60 years old), seeking for more effective method for cervical cancer screening. Methods: This is a cross-sectional study enrolled women who were referred to colposcopy and cervical histological examination due to abnormal cytology or HPV tests from Shanghai Sixth People's Hospital between January 2018 and December 2022. Results: A total of 1,931 women (mean age: 41.8 ± 12.5, range: 18-88 years old) were enrolled, 119 individuals aged ≥ 60 and 1732 aged <60. The infection rates of HPV52, 33, 35, 56, 26 and 81 were significantly higher in the elderly group. Multiple HPV infection rates were also higher in this group and were associated with cervical lesions. The probability of LSIL, HSIL and Ca in women over 60 years old was significantly higher compared to women under 60. The top three HPV genotypes in elderly women with CIN2+ were HPV16, 52, and 58. The Yoden index was higher for extended typing for HPV 31/33/45/52/58(0.41) compared to cytology(0.29), high risk HPV without specific typing(0.07), cotest(cytology and high risk HPV, 0.06 or 0.30), or the current shunt strategy(0.07). Conclusions: Elderly women still need to continue cervical cancer screening, and extended typing test for HPV16/18/31/33/45/52/58 is a more effective method for this age group.

Electrophysiological indexes of ingroup bias in a group Stroop task: Evidence from an event-related potential study.

Although cognitive system assigns higher attentional resources to ingroup information than outgroup information, but it is unclear whether the ingroup bias can be measured by the processes that are related to allocation of attentional resources to ingroup information. Thus, a group Stroop task was developed to study the issues combining with event-related potential (ERP) technique in this study. Specifically, 34 subjects (17 female, mean age = 20.76 ±â€¯1.26) were firstly divided into blue or red group (17 subjects for each group); then they were asked to categorize four words of Stroop task into "our team" or "other team" based on the ink color (blue/red) of the words whose meaning were also red/blue. The behavioral results showed that outgroup ink color processing was interfered by ingroup word meaning, but the ingroup ink color processing was less/not interfered by outgroup word meaning. The ERP results showed that the amplitude of frontal N100 was enhanced when more attentional resources were automatically captured by ingroup information in early stage than outgroup information; P2/N2 amplitude was reduced or enhanced when outgroup information processing was interfered by ingroup information; enhanced P3b amplitude reflected that attention could be more easily allocated to ingroup information than outgroup information based on target. This study implied a novel direction to study the neural basis of ingroup bias by investigating the roles of ingroup bias in assigning attentional resources to group information.

Therapeutic effect of human umbilical cord mesenchymal stem cells and their conditioned medium on LPS-induced endometritis in mice.

AIM: To explore the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) and their conditioned medium (MSC-CM) in repairing the endometritis mouse model in vivo. METHODS: Lipopolysaccharide (LPS) was used to induce acute inflammation in endometritis mouse model. Mice were treated in six groups: control group (PBS), model group (LPS), LPS+MSC-CM (6 h) group, LPS+MSC-CM (12 h) group, LPS+MSCs (6 h) group and LPS+MSCs (12 h) group. Morphological and histological changes of mouse uterus were observed, and mouse uterine inflammation index myeloperoxidase (MPO) and related immune index TNF-α, IL-6 and IL-1ß levels were detected by ELISA. RESULTS: There exist remarkable inflammatory response and an obvious increase in the value of MPO, TNF-α, IL-1ß and IL-6 in the endometritis mouse model compared with the control group. Morphological and histological appearances were relieved after treated with hUC-MSCs and MSC-CM. Besides, the value of MPO, TNF-α, IL-1ß and IL-6 showed different degrees of decline. In comparison with LPS+MSC-CM (12 h) and LPS+MSCs (12 h) group, there was significant decrease in inflammatory indicators in LPS+MSC-CM (6 h) and LPS+MSCs (6 h) group. CONCLUSIONS: Intrauterine infusion of hUC-MSCs and MSC-CM can alleviate LPS induced endometritis.

Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty.

This study aimed to compare the postoperative analgesic efficacy and motor recovery of a novel lumbar plexus block (LPB) with that of a femoral nerve block (FNB) after total knee arthroplasty (TKA). Forty patients who underwent TKA were randomised equally into an lumbar plexus and sciatic nerve (LS) group (receiving novel LPB) and an femoral and sciatic nerves (FS) group (receiving FNB). The assessed variables were the onset time of pain, time to the first analgesic request, pain scores, motor block at 6, 12, and 24 h after TKA, and the number of patients receiving successful blockade for each branch of the lumbar plexus. In the LS group, the femoral, lateral femoral cutaneous, genitofemoral, iliohypogastric, ilioinguinal, and obturator nerves were blocked in 18, 20, 16, 18, 15, and 19 patients. Compared to the FS group, the LS group had a significantly shorter onset time of pain and time to the first analgesic request, a significantly larger total postoperative dose of sufentanil, significantly higher numeric rating scale scores for both rest and dynamic pain at 6, 12, and 24 h, and faster motor recovery. Novel ultrasound-guided LPB has a high blocking success rate and provides inferior postoperative analgesia, but faster motor recovery after TKA than FNB.

PRPF19 promotes the proliferation, migration, and inhibits autophagy in prostate cancer by suppressing SLC40A1.

Prostate cancer (PCa) is a common cancer and the leading cause of cancer-related death in men. To investigate the role of pre-mRNA processing factor 19 (PRPF19) in proliferation, migration of PCa, and evaluate the potential ability of PRPF19 as a therapeutic target. PRPF19 expression was analyzed from The Cancer Genome Atlas and GEPIA databank. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the transcription of PRPF9 and solute carrier family 40 member 1 (SLC40A1). Immunohistochemistry (IHC) was used to test PRPF9 expression in PCa tissues. The cell viability and 5-ethynyl-2'-deoxyuridine incorporation analysis were performed to assess cell proliferation. Transwell assay was performed to investigate the migration and invasion of cancer cells. Western blot was used to measure the expression level of PRPF9, E-cadherin, Vimentin and α-smooth muscle actin (α-SMA), SLC40A1, LC3, Beclin-1 and ATG7. Immunofluorescence assay was performed to measure LC3 expression in PCa cells. The bioinformatic analysis revealed PRPF19 was highly expressed in PCa which was certified by qRT-PCR, western blot and IHC detection in PCa tissues. The proliferation of PCa cells could be promoted by PRPF19 overexpression and suppressed by PRPF19 knockdown. Moreover, the migration and invasion of PCa cells could be positively regulated by PRPF19 which promoted the expression of E-cadherin, Vimentin, and α-SMA. Furthermore, the expression of LC3, Beclin-1, and ATG7 was negatively regulated by PRPF19, indicating that PRPF19 inhibited autophagy in PCa cells. In the double knockdown of PRPF19 and SLC40A1, PRPF19 repressed the mRNA and reduced protein level of SLC40A1, and SLC40A1 antagonized effects of PRPF19 on proliferation, migration and autophagy of PCa cells. PRPF19 promoted proliferation and migration, and inhibited autophagy in PCa by attenuating SLC40A1 expression, indicating PRPF19 was a potential therapeutic target for PCa treatment.

YAP suppresses human T-cell leukemia virus type 1 transcription.

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATL). HTLV-1 encodes Tax protein that activates transcription from viral long terminal repeats (LTR). Multiple cofactors are involved in the regulation of HTLV-1 transcription via association with Tax. Yes-associated protein (YAP), which is the key effector of Hippo pathway, is elevated and activated in ATL cells. In this study, we reported that YAP protein suppressed Tax activation of HTLV-1 5' LTR but not 3' LTR. The activation of the 5' LTR by Tax was potentiated when YAP was depleted. Moreover, overexpression of YAP repressed HTLV-1 plus-strand viral gene expression and virion production, whereas compromising YAP by RNA inference augmented the expression of HTLV-1 protein. As mechanisms of YAP-mediated viral transcription inhibition, we found that YAP interacted with Tax, and prevented the association between Tax and p300. It finally led to the inhibition of recruitment of Tax to the Tax-responsive element in the 5' LTR of HTLV-1. Taken together, our results demonstrate the negative regulatory function of YAP in Tax activation of HTLV-1 transcription. It may achieve sufficient transcriptional repression to maintain persistent infection and long-term latency of HTLV-1 in the host cells.

Transcriptomic, 16S ribosomal ribonucleic acid and network pharmacology analyses shed light on the anticoccidial mechanism of green tea polyphenols against Eimeria tenella infection in Wuliangshan black-boned chickens.

BACKGROUND: Eimeria tenella is an obligate intracellular parasitic protozoan that invades the chicken cecum and causes coccidiosis, which induces acute lesions and weight loss. Elucidating the anticoccidial mechanism of action of green tea polyphenols could aid the development of anticoccidial drugs and resolve the problem of drug resistance in E. tenella. METHODS: We constructed a model of E. tenella infection in Wuliangshan black-boned chickens, an indigenous breed of Yunnan Province, China, to study the efficacy of green tea polyphenols against the infection. Alterations in gene expression and in the microbial flora in the cecum were analyzed by ribonucleic acid (RNA) sequencing and 16S ribosomal RNA (rRNA) sequencing. Quantitative real-time polymerase chain reaction was used to verify the host gene expression data obtained by RNA sequencing. Network pharmacology and molecular docking were used to clarify the interactions between the component green tea polyphenols and the targeted proteins; potential anticoccidial herbs were also analyzed. RESULTS: Treatment with the green tea polyphenols led to a reduction in the lesion score and weight loss of the chickens induced by E. tenella infection. The expression of matrix metalloproteinase 7 (MMP7), MMP1, nitric oxide synthase 2 and ephrin type-A receptor 2 was significantly altered in the E. tenella infection plus green tea polyphenol-treated group and in the E. tenella infection group compared with the control group; these genes were also predicted targets of tea polyphenols. Furthermore, the tea polyphenol (-)-epigallocatechin gallate acted on most of the targets, and the molecular docking analysis showed that it has good affinity with interferon induced with helicase C domain 1 protein. 16S ribosomal RNA sequencing showed that the green tea polyphenols had a regulatory effect on changes in the fecal microbiota induced by E. tenella infection. In total, 171 herbs were predicted to act on two or three targets in MMP7, MMP1, nitric oxide synthase 2 and ephrin type-A receptor 2. CONCLUSIONS: Green tea polyphenols can directly or indirectly regulate host gene expression and alter the growth of microbiota. The results presented here shed light on the mechanism of action of green tea polyphenols against E. tenella infection in chickens, and have implications for the development of novel anticoccidial products.

Catalytic Desymmetrizing Baeyer-Villiger Oxidation of Quaternary Carbon-Containing Cyclobutane-1,3-diones.

The first highly enantioselective Baeyer-Villiger oxidation of quaternary carbon-containing cyclobutane-1,3-diones using chiral phosphoric acid catalysis and commercially available oxidants was reported. According to the structure of the substrates, two optimized reaction conditions were developed to afford the corresponding chiral tetronic acid products in ≤93% and ≤95% ee values. This reaction offers the first catalytic asymmetric approach to chiral 5,5-disubstituted tetronic acid derivatives. The synthetic potential of this method has been demonstrated by the formal asymmetric synthesis of (-)-vertinolide and the first catalytic asymmetric total synthesis of plakinidone B.

Extracellular Vesicles Derived From Hypoxia-Treated Human Adipose Stem Cells Increase Proliferation and Angiogenic Differentiation in Human Adipose Stem Cells.

BACKGROUND: Adipose-derived stem cells (ADSCs) are crucial in cell-assisted lipotransfer (CAL). ADSC-derived exosomes could improve the survival of CAL. Almost all relevant research now ignores ADSCs in favor of studying the proangiogenic potential of extracellular vesicles (EVs) on human umbilical vein endothelial cells (HUVECs). OBJECTIVES: Given the significance of ADSCs in CAL, the authors sought to verify that EVs from ADSCs under hypoxia treatment can enhance the angiogenic potential of ADSCs. METHODS: EVs were harvested from human ADSCs (hADSCs) under normoxia and hypoxia. A Cell Counting Kit-8 (CCK-8) assay was used to measure the proliferation of hADSCs. By examining the expression of CD31, vascular endothelial growth factor receptor 2, and vascular endothelial growth factor, the pro-angiogenic differentiation potential was assessed. Moreover, a tube formation experiment was carried out to evaluate the pro-angiogenic differentiation potential. RESULTS: Hypoxic EVs showed more significant pro-proliferative and pro-angiogenic potential. Angiogenesis was more vigorous in hADSCs treated with hypoxic EVs than in those treated with nomorxic EVs. The hADSCs treated with hypoxic EVs expressed higher angiogenic markers, according to real-time polymerase chain reaction (RT-PCR) and Western blot analysis, which revealed more angiogenic marker expression in hypoxic EV-treated hADSCs. The same result was demonstrated by tube formation on Matrigel in vitro. CONCLUSIONS: Hypoxic EVs significantly increased the proliferation and angiogenic differentiation potential of hADSCs. Hypoxic EV-treated ADSCs may be beneficial to CAL and prevascularized tissue-engineered constructs.

Molecular Epidemiological Investigation of Cyclospora spp. in Holstein Cattle in Partial Areas of the Yunnan Province, China.

Cyclospora spp. is a food-borne intestinal protozoan, which is widely distributed in the world and poses the risk of zoonosis. In order to reveal the prevalence of Cyclospora spp. in Holstein cattle in partial areas of the Yunnan Province, 524 fresh fecal samples of Holstein cattle were collected from Dali, Kunming, Chuxiong, and Qujing in Yunnan Province. A nested PCR amplification of the small subunit (SSU) rRNA gene of Cyclospora spp. was carried out, and the products of the nested PCR were further analyzed by restriction fragment length polymorphism (RFLP) using Bsp E Ⅰ. The results of the present study showed that 13 samples were positive for Cyclospora spp., and the total infection rate of Cyclospora sp. was 2.48%. The infection of Cyclospora spp. was detected in Dali, Qujing, and Chuxiong. Chuxiong showed the highest infection rate (5.71%), and infection rate in Dali and Qujing was 2.19% and 3.16%, respectively. Interestingly, the infection of Cyclospora spp. was not detected in Kunming. The infection of Cyclospora spp. showed no significant differences among different regions (p > 0.05). Cyclospora sp. infection was detected in all ages and sexes, but the differences were not significant (p > 0.05). Sequencing and phylogenetic analysis showed that five Cyclospora spp. samples were closely related to the Cyclospora spp. of humans, and the others were closely related to the Cyclospora spp. of bovines. The results of the present study suggested that there was an infection of Cyclospora spp. in Holstein cattle in the Yunnan Province, and the Cyclospora spp. showed a risk of zoonosis. Thus, the prevention and control of Cyclospora spp. should be strengthened in the Yunnan Province, China. The results of this investigation provide data references for the further research of Cyclosporiasis in Holstein cattle in the Yunnan Province.

Quantitative association of cerebral blood flow, relaxation times and proton density in young and middle-aged primary insomnia patients: A prospective study using three-dimensional arterial spin labeling and synthetic magnetic resonance imaging.

Objectives: To quantitatively measure the T1 value, T2 value, proton density (PD) value, and cerebral blood flow (CBF) in young and middle-aged primary insomnia (PI) patients, and analyze the correlations between relaxation times, PD, and CBF to explore potential brain changes. Methods: Cranial magnetic resonance (MR) images of 44 PI patients and 30 healthy subjects were prospectively collected for analysis. The T1, T2, PD, and CBF values of the frontal lobe, parietal lobe, temporal lobe, and occipital lobe were independently measured using three-dimensional arterial spin labeling (3D-ASL), synthetic magnetic resonance imaging (syMRI) and a whole-brain automatic segmentation method. The differences of these imaging indices were compared between PI patients and healthy subjects. Follow-up MR images were obtained from PI patients after 6 months to compare with pre-treatment images. The Wilcoxon signed rank test and Spearman rank were used for statistical analysis. Results: Bilateral CBF asymmetry was observed in 38 patients, with significant differences in both the T2 value and CBF between the four lobes of the brain (p < 0.01). However, no significant difference was found in the T1 and PD values between the bilateral lobes. A negative correlation was found between CBF and T2 values in the right four lobes of patients with primary insomnia (PI). During follow-up examinations, five PI patients showed a disappearance of insomnia symptoms and a decrease in CBF in both brain lobes. Conclusion: Insomnia symptoms may be associated with high CBF, and most PI patients have higher CBF and lower T2 values in the right cerebral hemispheres. The right hemisphere appears to play a critical role in the pathophysiology of PI. The 3D-ASL and syMRI technologies can provide a quantitative imaging basis for investigating the brain conditions and changes in young and middle-aged PI patients.

Identification of key genes and pathways associated with gender difference in osteonecrosis of the femoral head based on bioinformatics analysis.

OBJECTIVE: To identify different key genes and pathways between males and females by studying differentially expressed genes (DEGs). METHODS: The gene expression data of GSE123568 were downloaded from GEO database, including osteonecrosis of the femoral head (ONFH) samples from 3 females and 7 males, and DEGs between different gender were identified with R software. Protein-protein interaction (PPI) network was constructed to further analyze the interactions between overlapping DEGs, and finally, GO, KEGG and gene set enrichment analysis (GSEA) were conducted for enrichment analysis. RESULTS: 131 DEGs were identified between ONFH females and ONFH males, including 76 up-regulated genes and 55 down-regulated genes. And 10 hub genes were identified in PPI network, including SLC4A1, GYPA, CXCL8, IFIT1, GBP5, IFI44, IFI44L, IFIT3, KEL and AHSP. Functional enrichment analysis revealed that these genes were mainly enriched in cGMP-PKG signaling pathway, Fatty acid degradation, Non-alcoholic fatty liver disease, Systemic lupus erythematosus, Hematopoietic cell lineage and NO-cGMP-PKG signaling. CONCLUSIONS: NO-cGMP-PKG signaling may play an important role in the occurrence and development of ONFH. SLC4A1, GYPA, CXCL8, GBP5 and AHSP may be key genes associated with gender difference in the progression of ONFH, which may be ideal targets or prognostic markers for the treatment of ONFH.

Phytochemical Analysis and Anti-Ascaris suum Activity of Different Zanthoxylum Species In Vitro and In Vivo.

Zanthoxylum plants (ZPs), including multiple Chinese prickly ash species, are dual-purpose functional foods favored by the general population around the world in foods, cosmetics, and traditional medicines and have antipruritic, insecticidal, and fungicidal bioactivities. For the first time, the anti-roundworm bioactivity of ZPs and the active ingredients were compared and investigated. Through nontarget metabolomics following targeted quantitative analysis, qinbunamides, sanshools, sanshooel, asarinin, and sesamin were found to be the main different components of Zanthoxylum species. Coincidentally, the 12 chemical components were also the dominant anti-roundworm ingredients of ZP extracts. The extracts of three species of Chinese prickly ash (1 mg/mL) decreased the hatchability of roundworm eggs significantly, and the ChuanJiao seed killed roundworms (insecticidal rate 100%) and alleviated the symptoms of pneumonia in mice. Furthermore, retention time-accurate mass-tandem mass spectrometry-ion ratio (RT-AM-MS/MS-IR) were modeled by assaying 108 authentic compounds of ZP extracts, and 20 metabolites were confidently identified in biological samples from ZP extract-treated mice by analyzing the m/z values and the empirical substructures. This study provides a good reference for the proper application of ZPs.

Factors associated with prolonged duration of ultrasound-guided brachial plexus block for the upper limb fracture surgery: a cross-sectional study.

Background: Previous studies of factors associated with prolonged duration of ultrasound-guided brachial plexus block have included multiple surgical procedures or multiple anesthetic approaches, all of which are important confounders, and there is no study based on a single method of anesthesia exploring the factors affecting the resolution of brachial plexus block during upper limb surgery, especially in Asians. This study aimed to identify the risk factors affecting the prolonged duration of US-guided brachial plexus block in American Society of Anesthesiologists (ASA) I-II grade patients to improve postoperative analgesia. Methods: This study enrolled patients scheduled to undergo surgery for upper limb fracture in Anting Hospital, Shanghai from May 2021 to September 2021. Inclusion criteria: (I) patients aged 18 years and above; (II) ASA I-II grade patients; (III) success of US-guided brachial plexus block. Based on the median duration of brachial plexus block, patients were divided into a <5-hour group and a ≥5-hour group. The factors were selected base on previous studies conclution and clinical demographic characteristics of patients. Multivariable logistic regression was used to estimate relevant influencing factors. Results: A total of 129 patients (51.2% males; 51.01±16.54 years old) were analyzed. The duration of brachial plexus block was 2-12 hours, with a median duration of 5.09 hours. Multivariable analysis suggested that age 40-49 years [odds ratio (OR): 4.841; 95% confidence interval (CI): 1.033 to 22.695; P=0.045], 50-59 years (OR: 4.730, 95% CI: 1.149 to 19.474; P=0.031), 60 years (OR: 8.540; 95% CI: 1.605 to 45.449; P=0.012), gender (OR: 3.314; 95% CI: 1.330 to 8.257; P=0.010), alanine aminotransferase (ALT; OR: 5.817, 95% CI: 1.509 to 22.472; P=0.011), and glomerular filtration rate (GFR) <60 (OR: 22.700; 95% CI: 1.994 to 198.386; P=0.012) were the risk factors for the duration of brachial plexus block. Conclusions: It is advisable to use the lowest effective dose for the shortest possible time when using ropivacaine in upper limb fracture surgery patients with elevated ALT (≥40 U/L) and lower GFR (<60 mL/min) in male patients aged ≥60 years.

Repurposing of the FGFR inhibitor AZD4547 as a potent inhibitor of necroptosis by selectively targeting RIPK1.

Necroptosis is a form of regulated necrosis involved in various pathological diseases. The process of necroptosis is controlled by receptor-interacting kinase 1 (RIPK1), RIPK3, and pseudokinase mixed lineage kinase domain-like protein (MLKL), and pharmacological inhibition of these kinases has been shown to have therapeutic potentials in a variety of diseases. In this study, using drug repurposing strategy combined with high-throughput screening (HTS), we discovered that AZD4547, a previously reported FGFR inhibitor, is able to interfere with necroptosis through direct targeting of RIPK1 kinase. In both human and mouse cell models, AZD4547 blocked RIPK1-dependent necroptosis. In addition, AZD4547 rescued animals from TNF-induced lethal shock and inflammatory responses. Together, our study demonstrates that AZD4547 is a potent and selective inhibitor of RIPK1 with therapeutic potential for the treatment of inflammatory disorders that involve necroptosis.

Seroprevalence and risk factors of Toxoplasma gondii and Neospora caninum infection in black goats in Yunnan Province, Southwestern China.

Toxoplasma gondii and Neospora caninum are two obligate intracellular protozoan parasites that can cause reproductive failure and production losses. To date, there is no data of T. gondii and N. caninum seroprevalence in black goats in Yunnan Province, southwestern China. In the present study, a total of 734 serum samples were collected from black goats in four different counties of Yunnan Province. 734 and 590 serum samples were examined for antibodies against T. gondii and N. caninum by using MAT and indirect ELISA, respectively. A total of 123 and 76 samples were T. gondii-positive and N. caninum-positive, respectively. The overall seroprevalence of T. gondii in black goats was 16.76% (123/734, 95% CI: 14.06-19.46) with the titer ranged from 1:25 to 1:3200. The seroprevalence of N. caninum was 12.88% (76/590, 95% CI: 10.18-15.58). There was significant difference in seroprevalence of N. caninum in different regions (P < 0.01, χ2 = 30.63) and age groups (P < 0.05, χ2 = 11.85). Significant differences in seroprevalence of T. gondii were observed in different regions (P < 0.05, χ2 = 9.21) and different gender groups (P < 0.01, χ2 = 12.29). Results of seroprevalence of T. gondii and N. caninum indicated that T. gondii and N. caninum were prevalent parasites in black goats in Yunnan Province. This is the first report of seroprevalence of T. gondii and N. caninum in black goats in Yunnan Province. The results of this study indicated that some measures should be taken to control these two parasites and to reduce economic losses to the livestock industry in Yunnan Province.

Self-reference processing of fat-face and sick-face in individuals with different disgust sensitivity: Evidence from behavioral and neuroelectrophysiology.

Self-reference effect has been widely discussed. Previous scholars believed that self-related information can be processed faster is due to the positive attribute of self-concept which speeds up self-related information processing. When self-related information is given negative attributes, the self-reference effect will be weakened. In this study, fat and sick, two kinds of stimuli associated with disgust characteristics, were added to self- and other-faces. We found that disease stimuli, which are closely related to survival threats, eliminated the self-reference effect while the obesity stimuli only weakened the self-reference effect to a certain extent. Event-related potential (ERP) analysis demonstrated that sick-faces have a greater amplitude than standard-faces in the EPN and LPP components. We believe that this may be due to the urgency of the disease threat, which leads to the selective attention to the disease threat in the early perception stage and the allocation of more attention resources for rapid response in the later stage. In addition, we found that disgust sensitivity specifically maintains individuals' self-referential effects by dissociating individuals from others in disease contexts. These results further support the behavioral immune function of disgust as a gatekeeper of the self in potentially contaminated environments. In conclusion, our study showed that in the face of survival threat, the self-reference effect is eliminated, and disgust tried to slow down this elimination effect to protect self. This study extends the behavioral immunity theory to some extent and further deepens the understanding of the relationship between disgust and self.

The Association Between Long-Term Spicy-Food Consumption and the Incidence of Chronic Postsurgical Pain After Cesarean Delivery: An Observational Study.

Background: Our previous study found that a long-term diet incorporating spicy foods can reduce the human basal pain threshold. Capsaicin is the pungent ingredient in chili peppers. Transient receptor potential vanilloid type1 is the capsaicin receptor expressed in the oral cavity and is the primary sensory neuron of the "pain" pathway. Few studies have examined the association between long-term spicy diet and chronic postsurgical pain (CPSP). Women who underwent elective cesarean section (eCS) have consistent characteristics of CPSP. This study aimed to investigate the relationship between a long-term spicy diet and the incidence of CPSP after eCS. Methods: Participants were divided into a low frequency group (LF, numerical rating scale (NRS)<5) for spicy food consumption and a high frequency group (HF, NRS≥5) by receiver operator characteristic analysis. The primary outcome was the incidence of CPSP three months after eCS. Propensity score matching (PSM) analysis was performed between the two frequency groups. Stepwise logistic regression analysis was then performed. Results: Of the 1029 enrolled patients, data from 982 were analyzed 3 months after eCS. After PSM, the incidence of CPSP in the HF group (30.1% [108/359]) was higher than that in the LF group (19.8% [71/359]; P = 0.001). Compared with the LF group, the risk of CPSP in the HF group increased 1.61 times by 3 months (95% CI 1.18-2.20, P = 0.003). PSM results found that 1 year, the incidence of CPSP in the HF group (15.2% [56/369]) was higher than that in the LF group (8.1% [30/369], P = 0.003). Conclusion: With an NRS≥5 as a boundary, women who consumed spicy food ≥ 2 days/week were more likely to have CPSP than those who consumed spicy food < 2 days/week.