Differences in Contents and Formation Methods of Clinical Questions in Chinese and Korean Clinical Practice Guidelines of Acupuncture-Moxibustion: Scoping Review.

OBJECTIVE: To analyze the differences in the needs of users and the value orientation of clinical practice guidelines (CPGs) by comparing the contents and formation methods of clinical questions in Chinese and Korean CPGs of acupuncture-moxibustion (Acup-Mox). METHODS: The full text of CPGs was systematically searched from the official websites of Chinese and Korean traditional medicine societies and Acup-Mox associations, with the topic "Acup-Mox for treating diseases" and the retrieval time up to September 28, 2022. Two researchers screened the CPGs independently, and extracted the guidelines' topics, content, quantity and formation methods of clinical questions. The quantitative data were collected by counting the frequency, and the qualitative data were classified and described by thematic analysis. RESULTS: A total of 29 guidelines were included in this study, including 20 Chinese guidelines (305 questions) and 9 Korean guidelines (223 questions). The differences lie in the aspects of content and diversity, and formation method. As for content and diversity, Chinese guidelines focused mainly on the questions related to treatment such as the operation of specific intervention (86, 28.2%), efficacy of intervention (78, 25.6%), and also involving questions in diagnosis, prevention, and prognosis. While the clinical questions in Korean guidelines were concentrated to efficacy of intervention (218, 97.8%). As for formation method, in Chinese guidelines, questions were usually collected directly from clinicians, and then determined and optimized by experts. In Korean guidelines, frequently used clinical Acup-Mox interventions would be screened first. Then the expert group would set up corresponding intervention control measures so as to form clinical questions related to treatment efficacy. CONCLUSIONS: The differences reflect the different needs of clinical practitioners, and the different aims or concepts in developing Acup-Mox guidelines between China and South Korea. Chinese guidelines emphasized promoting operation protocols and techniques of Acup-Mox for practical use, while Korean guidelines emphasized promoting the frequently used clinical intervention therapies. It is speculated that the guidelines from these two countries would play different roles in guiding clinical operation and supporting medical decision. In terms of formation methods of clinical questions, it is suggested to attach importance to optimizing process in formatting clinical questions to improve the clinical applicability of CPGs of Acup-Mox.

Development of a single LMS loop three channels analog adaptive co-site interference cancelling system.

Co-site interference is becoming prominent on some independent platforms (e.g., airplanes, satellites, space stations, and vessels). Although many digital multichannel cancellation algorithms have been investigated, the saturation problem of the receiver front-end caused by severe co-site interference should be addressed first with analog RF cancellation. Many studies are currently being conducted to develop an analog adaptive co-site interference cancellation system (AACICS). However, double LMS (Least Mean Square) loop in every channel raises the complexity and implemented difficulty. Above all, the interference cancellation in the scene of antenna swaying has received little attention, which severely limits the effective suppression of wideband interference. This study developed an analog 3-channel adaptive co-site wideband interference cancellation system (AACWICS-3ch) with one LMS loop in every channel and established the equivalent model of the AACWICS-3ch. The steady-state weight and interference cancellation ratio (ICR) were obtained by analyzing and solving the equivalent model. An in-depth analysis was conducted on the quantitative relationship correlations between the interference cancellation bandwidth, ICR, system gain, and antenna swing amplitude. Results reveal that AACWICS-3ch can greatly enhance the interference cancellation performance compared to 2-channel analog adaptive co-site interference cancellation system (AACICS-2ch). The maximum improved ICR is greater than 30 dB, and it overcomes the complexity of double LMS loop cancellation system with the increasing of channel. Finally, simulations and experiments validated the improvement of interference cancellation performance in AACWICS-3ch.

Codonopsis pilosula polysaccharides promote osteogenic differentiation and inhibit lipogenic differentiation of rat bone marrow stem cells by activating ß-catenin.

Aberrant bone marrow mesenchymal stem cell (BMSC) lineage differentiation leads to osteoporosis. Codonopsis pilosula polysaccharides (CPPs) have been widely used in traditional Chinese medicines, due to their multiple pharmacological actions. However, little is known regarding their effects on BMSC differentiation. This study aimed to identify the effects and mechanisms of CPPs on osteogenic and adipogenic differentiation in rat BMSCs. An osteoporosis model was established in Sprague-Dawley (SD) rats through bilateral ovariectomy (OVX), and be applied to observe the effect of CPPs on osteoporosis in vivo. The ability of CPPs to affect rBMSC proliferation was determined using the CCK-8 assay, and the osteogenic differentiation of rBMSCs measured by ALP and Alizarin Red S staining. The adipogenic differentiation of rBMSCs was measured by Oil Red O staining. The mRNA and protein levels related to osteogenesis and adipogenic differentiation of rBMSCs were measured using qRT-PCR and western blotting, respectively. Cellular immunofluorescence was used to detect cytokine expression and localisation in rBMSCs. We observed that CPPs ameliorated bone loss in OVX rats. CPPs considerably enhanced osteogenic differentiation by increasing ALP activity and the prevalence of mineralised nodules and promoting the mRNA and protein expression of osteogenic differentiation markers (RUNX2, COL I, ALP, and OPN). Furthermore, it inhibited the accumulation of lipid vesicles in the cytoplasm and the mRNA and protein expression levels of adipogenic differentiation markers (PPARγ and C/EBPα) in a concentration-dependent manner. Meanwhile, CPPs notably increased the mRNA and protein expression of ß-catenin, the core protein of the Wnt/ß-catenin signaling pathway, in a concentration-dependent manner. Adding DKK1, a mature inhibitor of the Wnt/ß-catenin signaling pathway, partially suppressed CPP-stimulated ß-catenin activation, and reversed the acceleration of osteogenic differentiation and the inhibition of lipogenic differentiation. Our observations demonstrated CPPs ameliorate bone loss in OVX rats in vivo, and favour osteogenic differentiation while inhibit adipogenic differentiation of rBMSCs in vitro. The findings suggested that CPPs could serve as functional foods for bone health, and have great potential for the prevention and treatment of osteoporosis.

Mussel-Inspired Wet-Adhesive Multifunctional Organohydrogel with Extreme Environmental Tolerance for Wearable Strain Sensor.

As a flexible artificial material, the conductive hydrogel has broad application prospects in flexible wearable electronics, soft robotics, and biomedical monitoring. However, traditional hydrogels still face many challenges, such as long-term stability, availability in extreme environments, and long-lasting adhesion to the skin surface under sweaty or humid conditions. To circumvent the above issues, one kind of ionic conductive hydrogel was prepared by a simple one-pot method that dissolved chitosan (CS), 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), tannic acid (TA), and 2-methoxy-ethyl acrylate (MEA) into dimethyl sulfoxide (DMSO)/H2O solvent. The resulting hydrogel showed excellent tensile properties (1440%), extreme environmental tolerance (-40-60 °C), adhesion (72 KPa at porcine skin), ionic conductivity (0.87 S m-1), and high-efficiency antibacterial property. Furthermore, the produced organohydrogel strain sensor exhibited high strain sensitivity (GF = 4.07), excellent signal sensing capabilities (human joint movement, microexpression, and sound signals), and long-term cyclic stability (400 cycles). Looking beyond, this work provides a simple and promising strategy for using hydrogel sensors in extreme environments for e-skin, health monitoring, and wearable electronic devices.

Deep learning for real-time detection of nasopharyngeal carcinoma during nasopharyngeal endoscopy.

Nasopharyngeal carcinoma (NPC) is known for high curability during early stage of the disease, and early diagnosis relies on nasopharyngeal endoscopy and subsequent pathological biopsy. To enhance the early diagnosis rate by aiding physicians in the real-time identification of NPC and directing biopsy site selection during endoscopy, we assembled a dataset comprising 2,429 nasopharyngeal endoscopy video frames from 690 patients across three medical centers. With these data, we developed a deep learning-based NPC detection model using the you only look once (YOLO) network. Our model demonstrated high performance, with precision, recall, mean average precision, and F1-score values of 0.977, 0.943, 0.977, and 0.960, respectively, for internal test set and 0.825, 0.743, 0.814, and 0.780 for external test set at 0.5 intersection over union. Remarkably, our model demonstrated a high inference speed (52.9 FPS), surpassing the average frame rate (25.0 FPS) of endoscopy videos, thus making real-time detection in endoscopy feasible.

Adverse childhood experiences in patients with schizophrenia: related factors and clinical implications.

The relationship between adverse childhood experiences (ACEs) and the development of psychotic symptoms is not well understood. Therefore, this study aimed to investigate the frequency and distribution of ACEs among patients with schizophrenia and their potential correlation with symptomatology and personality pathology. We conducted a cross-sectional study involving 571 patients with schizophrenia in Shanghai, China. Symptomatology was assessed using the Positive and Negative Symptoms Scale (PANSS) and personality pathology was assessed using the Personality Diagnostic Questionnaire Fourth Edition Plus (PDQ-4+). ACEs were assessed using the Child Trauma Questionnaire-Short Form (CTQ-SF). ACEs were highly prevalent, with 80.8% of the patients with schizophrenia reporting at least one ACE. The three most common types of ACE were physical neglect (69.8%), emotional neglect (28.2%), and emotional abuse (22.9%). For specific ACE, emotional abuse was significantly associated with PD traits, whereas emotional and physical neglect types of ACE was significantly associated with negative symptoms. A higher level of physical abuse was more commonly reported by men, younger individuals, and those with a higher level of antisocial PD traits. Higher levels of physical neglect were associated with more severe negative symptoms. ACEs are commonly observed in patients with schizophrenia. Therefore, it is strongly recommended that this clinical population be provided with a comprehensive assessment and individualized intervention for those exposed to specific ACEs.

Treatment-related outcome from patient report outcome (PRO) of children with severe and moderate hemophilia A in China: An analysis report of registration data from patient organization "hemophilia home care center".

OBJECTIVES: To assess current treatment-related outcomes for children with severe and moderate haemophilia A (cHA) in China. METHODS: This cross-section Patient Report Outcome (PRO) report collected PRO data of severe and moderate cHAs registered in the 'Hemophilia Home Care Center' database (http://web.bjxueyou.cn) between January 2021 and November 2022. Data included records of bleeding, activities, and concentrates consumption. All patients had a confirmed diagnosis of moderate or severe haemophilia A (FVIII: C ≤ 5%) and were < 18 years old. RESULTS: Among 1038 analysable cases, 9.6% of children with inhibitors had a higher rate of intracranial haemorrhage, dropout school rate, and higher FVIII consumption than children without inhibitors. Among 100 children with inhibitors, 36 patients were treated without immune tolerance induction (ITI), 14 patients with irregular treatment and 50 patients received ITI. Children with ITI had a lower ABR (2.4 (0,6.6) vs. 13.4 (9.5, 26.6), p<.001) and AJBR (0 (0, 3.1) vs. 8.9 (1.6, 19.3), p < .001) compared to those without ITI. Among 938 children without inhibitors, 28.5% received on-demand treatment and 71.5% received prophylaxis. Of 528 children with 1343.8 (1050.4, 2922.9)IU/kg/year median FVIII consumption, 43.0% received low-dose, 43.2% received intermediate-dose, and 13.8% received high-dose regimen; these children with prophylaxis had a lower ABR (3.1 (0, 10.7) vs. 12.8 (2.4, 45.5), p < .001), AJBR (0.5 (0, 3.9) vs. 3.0 (0, 12.0), p < .001) and disability rate (9.0% vs.18.5%, p = .032) compared to children who received on-demand treatment. CONCLUSION: The high rate of drop-out of school and disability still present a huge gap to meet the needs in China. It is necessary to improve the level of medical accessibility and medicine affordability and strengthen the patient/parent's education in China.

Validation of a metabolite-GWAS network for Populus trichocarpa family 1 UDP-glycosyltransferases.

Metabolite genome-wide association studies (mGWASs) are increasingly used to discover the genetic basis of target phenotypes in plants such as Populus trichocarpa, a biofuel feedstock and model woody plant species. Despite their growing importance in plant genetics and metabolomics, few mGWASs are experimentally validated. Here, we present a functional genomics workflow for validating mGWAS-predicted enzyme-substrate relationships. We focus on uridine diphosphate-glycosyltransferases (UGTs), a large family of enzymes that catalyze sugar transfer to a variety of plant secondary metabolites involved in defense, signaling, and lignification. Glycosylation influences physiological roles, localization within cells and tissues, and metabolic fates of these metabolites. UGTs have substantially expanded in P. trichocarpa, presenting a challenge for large-scale characterization. Using a high-throughput assay, we produced substrate acceptance profiles for 40 previously uncharacterized candidate enzymes. Assays confirmed 10 of 13 leaf mGWAS associations, and a focused metabolite screen demonstrated varying levels of substrate specificity among UGTs. A substrate binding model case study of UGT-23 rationalized observed enzyme activities and mGWAS associations, including glycosylation of trichocarpinene to produce trichocarpin, a major higher-order salicylate in P. trichocarpa. We identified UGTs putatively involved in lignan, flavonoid, salicylate, and phytohormone metabolism, with potential implications for cell wall biosynthesis, nitrogen uptake, and biotic and abiotic stress response that determine sustainable biomass crop production. Our results provide new support for in silico analyses and evidence-based guidance for in vivo functional characterization.

Experimental study on the effect of caffeine hydrogel on the expression of TGF -ß1, α-SMA and collagen in hypertrophic scar of rabbit ears.

This study evaluated the effects of topical use of caffeine hydrogel on hypertrophic scar in a rabbit ear wound model. Nine rabbits were randomly divided into three groups: control group, caffeine hydrogel group and matrix group. Punched defects were established on each rabbit's ear which resulted in a hypertrophic scar. When the wound epithelialization and scar hyperplasia could be seen, control group did not do any treatment, while caffeine hydrogel group and matrix group were treated with caffeine hydrogel and hydrogel matrix, respectively. After 3 weeks of administration, the general morphological changes of scar were observed, and the scar tissue of rabbit ears was stained with HE and Masson. The relative expressions of TGF ß-1, α-SMA, type Ⅰ collagen and type Ⅲ collagen in scar tissue were detected by Western blot. In all three groups, findings showed that caffeine hydrogel can inhibit scar growth by reducing the expression of TGF ß-1, reducing the proliferation of fibroblasts, improving collagen arrangement and reducing collagen deposition. The overall study shows efficacy and mechanism of caffeine. It concluded that caffeine could be an effective therapeutic agent for hypertrophic scars.

Secure semantic optical communication scheme based on the multi-head attention mechanism.

In this paper, an artificial-intelligence-based secure semantic optical communication scheme is proposed. The semantic features of the original text information are extracted using Transformer. Compared with other networks, Transformer reduces the complexity of the structure and the associated training cost by using the multi-head attention mechanism. To solve the security problem, the encryption scheme is applied to an orthogonal frequency division multiplexed passive optical network (OFDM-PON). The proposed scheme applies chaotic sequences to produce masking vectors. We encrypt the constellation and frequency, achieving a large key space of 1 × 10270. To prove that Transformer can effectively extract the semantic features of text, we have computed the values of ROUGE-1, ROUGE-2, and ROUGE-L, which are 40.9, 18.02, and 37.17, respectively. An encrypted 16 quadrature amplitude modulation (16QAM) OFDM signal transmission over a 2 km seven-core fiber with a data rate of 78.5 Gbits/s was experimentally demonstrated. During the experiments, the bit error rate (BER) was analyzed and the results show that the proposed system improves efficiency and security in an OFDM-PON system.

Occurrence of microplastics in Antarctic fishes: Abundance, size, shape, and polymer composition.

Presence of microplastics (MPs) in Antarctic ecosystems has attracted global attention, due to the potential threat to the Antarctic marine organisms. However, data on the occurrence of MPs in Antarctic fishes remains very limited. This study investigated the abundance and characteristics of MPs in four species of Antarctic fish (n = 114). The highest mean abundance of MPs was detected in Trematomus eulepidotus (1.7 ± 0.61 items/individual), followed by that in Chionodraco rastrospinosus (1.4 ± 0.26 items/individual), Notolepis coatsi (1.1 ± 0.57 items/individual), and Electrona carlsbergi (0.72 ± 0.19 items/individual). MPs in Notolepis coatsi (mean 747 µm) had the highest mean size, followed by that in Trematomus eulepidotus (653 µm), Chionodraco rastrospinosus (629 µm), and Electrona carlsbergi (473 µm). This is possibly attributed to the feeding habits and egestion behaviors of different Antarctic fishes. Fiber was consistently the predominant shape of MPs in Trematomus eulepidotus, Chionodraco rastrospinosus, and Electrona carlsbergi, accounting for 82 %, 76 %, and 60 % of total items of MPs, respectively. Polypropylene, polyamide, and polyethylene were the predominant polymer composition of MPs in Antarctic fishes, collectively contributed 63-86 % of total items of MPs. This may be because these types of MPs have been widely used in global household materials. To our knowledge, this is the most comprehensive study examining the occurrence of MPs in Antarctic fishes. This study provides fundamental data for evaluating the risks of MP exposure for Antarctic fishes.

The toxic mechanism of 6:2 Cl-PFESA in adolescent male rats: Endocrine disorders and liver inflammation regulated by the gut microbiota-gut-testis/liver axis.

In previous studies, 6:2 chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA), a perfluorooctanesulfonate alternative, has been demonstrated to be toxic to mammals. However, the toxic mechanism of 6:2 Cl-PFESA in mammals is unknown. Herein, adolescent male rats were administered 50 µg/kg/Day 6:2 Cl-PFESA for 28 days (oral gavage) to estimate the toxicity of 6:2 Cl-PFESA and investigate its toxic mechanism. Significant changes in some hematological indicators (e.g., aspartate transaminase and neutrophils) and liver sections (inflammatory cell infiltration) indicated that 6:2 Cl-PFESA exposure caused rat hepatotoxicity. Six steroid hormones (e.g., testosterone, progesterone, and cortisol) in serum and thirteen genes in testicles (related to the pathway of steroid hormone biosynthesis) were significantly regulated in 6:2 Cl-PFESA-treated rats. This suggested that 6:2 Cl-PFESA induced rat endocrine disorders. Compared to the controls, the mean relative abundance of Ruminococcaceae, Pasteurellaceae, Micrococcaceae, and Desulfovibrionaceae was significantly regulated by 1.3-, 0.40-, 0.32-, and 3.2-fold in the 6:2 Cl-PFESA rats, respectively. The 6:2 Cl-PFESA treatment also significantly disturbed 47 gut metabolites (29 upregulated and 18 downregulated), mainly bile acids, short-chain fatty acids, and amino acids. In summary, 6:2 Cl-PFESA induced endocrine disorders and liver inflammation in rats by altering the gut microbiota-gut-testis/liver axis. This study first reveals the toxic mechanism of 6:2 Cl-PFESA in mammals through a multiomics approach and provides comprehensive insight into the toxic mechanism of 6:2 Cl-PFESA.

The effectiveness of sewage sludge biochar amendment with Boehmeria nivea L. in improving physicochemical properties and rehabilitating microbial communities in mine tailings.

Biochar amendment can be adopted to improve soil substrate, in turn facilitated phytoremediation. However, improvements to the properties of tailings following different feedstocks of biochar amendment in phytoremediation, particularly the impacts on nitrogen cycle and the related nitrogen-fixing microorganisms remain unclear. In this study, a 100-day pot experiment was designed to determine the co-effects of different combinations of woody and non-woody biochar, namely hibiscus cannabinus core biochar (HB), sewage sludge biochar (SB), chicken manure biochar (MB) and two crops (Cassia alata L., Boehmeria nivea L.). It was found that, on the one hand, biochar amendment directly immobilized heavy metal (loid) contamination in the tailings; on the other hand, biochar amendment, particularly non-woody SB, improved soil properties (i.e., the combination of SB with crops increased the total nitrogen content by 4.7-7.5 times). This indirectly improved phytostabilization (i.e., SB increased crop height 1.5-1.8 fold, root length 3.3-3.7 fold, decreased NH4NO3-extractable Pb, Cu, Cd and also increased the relative abundance of nitrogen-fixing bacteria such as Mesorhizobium, Bradyrhizobium, and Rhizobium). Besides this, redundant analysis shown that the carbon, nitrogen sources, and pH provided by the biochar were identified as the key factors associated with the nitrogen-fixing bacteria. Through the comprehensive evaluation of different biochar amendment in phytoremediation, it was found that the non-woody SB got higher comprehensive score (3.1-3.6) in biochar amendment in phytoremediation, especially in Boehmeria nivea L. Thus, the combination of non-woody SB and Boehmeria nivea L. improved microbial function, while the microorganisms in turn promoted crop growth. Our results revealed the prospect of using non-woody SB assisted Boehmeria nivea L. for phytoremediation in multi-metal mine tailings.

How does users' interest influence their click behavior?: evidence from Chinese online video media.

Interest is one of the main factors motivating an individual's behavior, and its effect in the learning process has been widely confirmed in educational psychology. The purpose of this study was to explore the influence of individual interest, topic interest and situational interest on the user's video click behavior in the online video browsing situation. We constructed an online experiment in which each participant was asked to use questionnaires to assess their responses to video categories, titles, and covers from the video-sharing website, Bilibili. Based on these responses, we obtained individual interests, topic interests, situational interests, and click behavior of the participants toward the videos. Correlation, regression and mediation analyses were conducted to explore the effects and mechanisms of the three interests on click behavior. The results found: (1) individual interest may have a positive but relatively weaker effect on click behavior, and (2) topic interest and situational interest positively predicted click behavior in all categories. The mediation analysis found: (1) in the otomads and fashion categories, the effect of individual interest on click behavior was partially mediated by topic and situational interest, and (2) in the anime, digits, life, dance, music, game, entertainment, and knowledge categories, the effect of individual interest on click behavior was fully mediated by topic interest and situational interest. These results revealed the facilitating effects and different effect modes of individual, topic, and situational interest on click behavior. These findings shed light on the influence mechanism of interests on video click behavior in different video categories and provide new insights into related applications such as recommender.

[Effects of transcutaneous electrical acupoint stimulation on the postoperative sleep quality and inflammatory factors in frail elderly patients].

OBJECTIVE: To observe the effects of transcutaneous acupoint stimulation (TEAS) on sleep quality and inflammatory factor in frail elderly patients undergoing laparoscopic colorectal cancer surgery. METHODS: A total of 100 frail elderly patients undergoing elective laparoscopic colorectal cancer surgery were randomly divided into an observation group and a control group, 50 cases in each one. Patients in the observation group received TEAS, 30 min before surgery until the end of surgery, at 18:00 on the day of surgery and on the 1st, 2nd and 3rd day after surgery (30 min each time). TEAS was delivered at bilateral Neiguan (PC 6), Shenmen (HT 7) and Hegu (LI 4). The disperse-dense wave of 2 Hz/100 Hz was selected, and the maximal stimulation intensity depended on patient's tolerance. The operation procedure in the control group was same as the observation group, but without electric stimulation exerted. The 1st day before surgery and on the 1st, 3rd and 7th day after surgery, the scores of Pittsburgh sleep quality index (PSQI) and Athens insomnia scale (AIS), as well as the serum levels of C reactive protein (CRP) and interleukin-6 (IL-6) were observed in the patients of two groups. At 24 h, 48 h and 72 h after surgery, the score of pain visual analogue scale (VAS) was recorded in the two groups, as well as the pressing times of analgesic pump and the usage of flurbiprofen axetil during analgesic stage. The occurrence of post operative adverse reactions was observed in the patients of two groups. RESULTS: On the 1st and 3rd day after surgery, except the usage of hypnotic drug scores, the scores of each item and the total scores of PSQI, as well as AIS scores were all increased in the two groups compared with those of 1 day before surgery (P<0.05); and the scores in the observation group were lower than those in the control group (P<0.05). On the 7th day after surgery, the scores of each item and the total scores of PSQI, and AIS scores were not different statistically in comparison between the two groups (P>0.05). On the 1st, 3rd and 7th day after surgery, serum levels of CRP and IL-6 were all increased in the patients of two groups when compared with those of 1 day before surgery (P<0.05), serum levels CRP and IL-6 in the patients of the observation group were lower than those of the control group (P<0.05). The VAS scores of 24 h, 48 h and 72 h after surgery, the pressing times of analgesic pump, the frequency and dosage of the remedies were not different statistically between the two groups (P>0.05). CONCLUSION: TEAS can effectively improve sleep quality and reduce inflammatory reaction in frail elderly patients undergoing laparoscopic colorectal cancer surgery.

Intracerebral Hemorrhage-Induced Brain Injury: the Role of Lysosomal-Associated Transmembrane Protein 5.

Intracerebral hemorrhage (ICH) is a lethal stroke with high mortality or disability. However, effective therapy for ICH damage is generally lacking. Previous investigations have suggested that lysosomal protein transmembrane 5 (LAPTM5) is involved in various pathological processes, including autophagy, apoptosis, and inflammation. In this study, we aimed to identify the expression and functions of LAPTM5 in collagenase-induced ICH mouse models and hemoglobin-induced cell models. We found that LAPTM5 was highly expressed in brain tissues around the hematoma, and double immunostaining studies showed that LAPTM5 was co-expressed with microglia cells, neurons, and astrocytes. Following ICH, the mice presented increased brain edema, blood-brain barrier permeability, and neurological deficits, while pathological symptoms were alleviated after the LAPTM5 knockdown. Adeno-associated virus 9-mediated downregulation of LAPTM5 also improves ICH-induced secondary cerebral damage, including neuronal degeneration, the polarization of M1-like microglia, and inflammatory cascades. Furthermore, LAPTM5 promoted activation of the nuclear factor kappa-B (NF-κB) pathway in response to neuroinflammation. Further investigations indicated that brain injury improved by LAPTM5 knockdown was further exacerbated after the overexpression of receptor-interacting protein kinase 1 (RIP1), which is revealed to trigger the NF-κB pathway. In vitro experiments demonstrated that LAPTM5 silencing inhibited hemoglobin-induced cell function and confirmed regulation between RIP1 and LAPTM5. In conclusion, the present study indicates that LAPTM5 may act as a positive regulator in the context of ICH by modulating the RIP1/NF-κB pathway. Thus, it may be a candidate gene for further study of molecular or therapeutic targets.

Hepatic interleukin 32 attenuates liver injury through repression of necroptosis in cholestasis.

OBJECTIVE: We aimed to evaluate the association between interleukin (IL)-32 and necroptosis in cholestatic liver injury. METHODS: Levels of necroptosis-related markers in cholestatic and control patients, including the receptor-interacting serine-threonine kinase 3 (RIPK3), receptor-interacting serine-threonine kinase 1 (RIPK1), and mixed lineage kinase domain-like (MLKL) were measured. Animal experiments in C57BL/6J and transgenic mice with IL32ß/γ overexpression were also conducted to confirm the effect of IL-32 on necroptosis in cholestasis, which was induced by α-naphthylisothiocyanate (ANIT) and 1% lithocholic acid (LCA). PLC/PRF/5-ASBT and primary mouse hepatocytes were utilized for the investigation of the regulation and mechanism of IL-32 in cholestasis. RESULTS: In the liver tissues of cholestatic patients, the mRNA and protein expressions of RIPK1, RIPK3, and MLKL were increased and associated with IL-32 expression. In addition, expressions of these indicators in the liver of 1% LCA- and ANIT-induced mouse models were significantly increased, while they were markedly decreased in hIL32ßLTg and hIL32γLTg mice. After bile acid stimulation, IL-32 and phosphorylated Akt (p-Akt) expressions significantly elevated in a dose-dependent manner. After treated with tumor necrosis factor (TNF)-α, IL-32 inhibited MLKL expression in primary mouse hepatocytes. CONCLUSION: IL-32 is negatively associated with necroptosis in cholestatic patients. Moreover, IL-32 is induced by p-Akt and effectively attenuates necroptosis in ANIT- or 1% LCA-induced cholestasis.

Polymorphonuclear myeloid-derived suppressor cells play a proinflammatory role via TNF-α+ B cells through BAFF/BTK/NF-κB signalling pathway in the pathogenesis of collagen-induced arthritis mice.

Although various studies have been performed on the function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in RA, the results were conflicting. Here we were trying to clarify the role of PMN-MDSCs in the pathogenesis of RA and its specific mechanisms. We detected the frequencies and counts of PMN-MDSCs, TNF-α+ B cells and Ki67+ B cells in spleen and inflamed joints of collagen-induced arthritis (CIA) mice using flow cytometry. The pathological role of PMN-MDSCs was examined by anti-Ly6G neutralizing antibodies against PMN-MDSCs or adoptive transfer of PMN-MDSCs. And the modulation of PMN-MDSCs on B cells was conducted by coculture assays, RNA-Seq, RT-qPCR, and so on. The mechanism of BAFF regulating B cells was verified through western blot and flow cytometry. PMN-MDSCs accumulated in the spleen and joints of CIA mice. PMN-MDSCs depletion could alleviate the arthritis severity, which was accompanied by decreased TNF-α secretion and proliferation of B cells. And its adoptive transfer also facilitated disease progress. Furthermore, PMN-MDSCs from CIA mice had higher expression level of BAFF, which regulated TNF-α expression, proliferation and apoptosis of B cells in vitro. What's more, BAFF promoted phosphorylation of BTK/NF-κB signalling pathway. And Ibrutinib (BTK inhibitor) could reverse the effect of BAFF on TNF-α expression of B cells. Our study suggested that PMN-MDSCs enhanced disease severity of CIA and manipulated TNF-α expression, proliferation and apoptosis of B cells via BAFF, furthermore, BAFF promoted TNF-α expression through BTK/NF-κB signalling pathway, which demonstrated a novel pathogenesis of PMN-MDSCs in CIA.