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Background. The pathogenesis of ankylosing spondylitis (AS) is still not clear, and immune-related genes have not been systematically explored in AS. The purpose of this paper was to identify the potential early biomarkers most related to immunity in AS and develop a predictive disease risk model with bioinformatic methods and the Gene Expression Omnibus database (GEO) to improve diagnostic and therapeutic efficiency. Methods. To identify differentially expressed genes and create a gene coexpression network between AS and healthy samples, we downloaded the AS-related datasets GSE25101 and GSE73754 from the GEO database and employed weighted gene coexpression network analysis (WGCNA). We used the GSVA, GSEABase, limma, ggpubr, and reshape2 packages to score immune data and investigated the links between immune cells and immunological functions by using single-sample gene set enrichment analysis (ssGSEA). The value of the core gene set and constructed model for early AS diagnosis was investigated by using receiver operating characteristic (ROC) curve analysis. Results. Biological function and immune score analyses identified central genes related to immunity, key immune cells, key related pathways, gene modules, and the coexpression network in AS. Granulysin (GNLY), Granulysin (GZMK), CX3CR1, IL2RB, dysferlin (DYSF), and S100A12 may participate in AS development through NK cells, CD8+ T cells, Th1 cells, and other immune cells and represent potential biomarkers for the early diagnosis of AS occurrence and progression. Furthermore, the T cell coinhibitory pathway may be involved in AS pathogenesis. Conclusion. The AS disease risk model constructed based on immune-related genes can guide clinical diagnosis and treatment and may help in the development of personalized immunotherapy.

With the rapid economic growth, China has officially entered into an aging society and is facing the severe challenge of a population aging crisis. China has begun implementing the Time Bank for old-age service to address the aging problem better. However, Time Bank is usually developed in economically developed regions, and Time Bank is not set in less developed areas. This paper compares and analyzes the operation mechanism of the Time Bank in Nanning from five perspectives: policy support and funding sources, operation model, volunteer team construction, Time Banking platform construction, and service projects. The proposed measures for developing Time Bank in less developed regions fill a problem gap. China needs to address the risk of population aging actively. This is important for China to solve its pension problem and deepen the understanding of Chinese academia on the development of time banking in less developed regions.

The mechanoelectrical transduction (MET) protein complex in the inner-ear hair cells is essential for hearing and balance perception. Calcium and integrin-binding protein 2 (CIB2) has been reported to be a component of MET complex, and loss of CIB2 completely abolishes MET currents in auditory hair cells, causing profound congenital hearing loss. However, loss of CIB2 does not affect MET currents in vestibular hair cells (VHCs) as well as general balance function. Here, we show that CIB2 and CIB3 act redundantly to regulate MET in VHCs, as MET currents are completely abolished in the VHCs ofCib2/Cib3double knock-out mice of either sex. Furthermore, we show thatCib2andCib3transcripts have complementary expression patterns in the vestibular maculae, and that they play different roles in stereocilia maintenance in VHCs.Cib2transcripts are highly expressed in the striolar region, and knock-out ofCib2affects stereocilia maintenance in striolar VHCs. In contrast,Cib3transcripts are highly expressed in the extrastriolar region, and knock-out ofCib3mainly affects stereocilia maintenance in extrastriolar VHCs. Simultaneous knock-out ofCib2andCib3affects stereocilia maintenance in all VHCs and leads to severe balance deficits. Taken together, our present work reveals that CIB2 and CIB3 are important for stereocilia maintenance as well as MET in mouse VHCs.SIGNIFICANCE STATEMENTCalcium and integrin-binding protein 2 (CIB2) is an important component of mechanoelectrical transduction (MET) complex, and loss of CIB2 completely abolishes MET in auditory hair cells. However, MET is unaffected inCib2knock-out vestibular hair cells (VHCs). In the present work, we show that CIB3 could compensate for the loss of CIB2 in VHCs, andCib2/Cib3double knock-out completely abolishes MET in VHCs. Interestingly, CIB2 and CIB3 could also regulate VHC stereocilia maintenance in a nonredundant way.Cib2andCib3transcripts are highly expressed in the striolar and extrastriolar regions, respectively. Stereocilia maintenance and balance function are differently affected inCib2orCib3knock-out mice. In conclusion, our data suggest that CIB2 and CIB3 are important for stereocilia maintenance and MET in mouse VHCs.

IL-10-producing regulatory B cells (IL-10TET2 activation in B cells triggered by oxidative stress from the HCC microenvironment promoted IL-10 expression, whereas adoptive transfer of Tet2-deficient B cells suppressed HCC progression. The aryl hydrocarbon receptor is required for TET2 to hydroxylate Il10. In addition, high levels of IL-10, TET2, and 5hmc in B cells indicate poor prognosis in patients with HCC. Moreover, we determined TET2 activity using 5hmc in B cells to evaluate the efficacy of anti-programmed death 1 (anti-PD-1) therapy. Notably, TET2 inhibition in B cells facilitates antitumor immunity to improve anti-PD-1 therapy for HCC.Our findings propose a TET2-dependent epigenetic intervention targeting IL-10

As the auditory and balance receptor cells in the inner ear, hair cells are responsible for converting mechanical stimuli into electrical signals, a process referred to as mechano-electrical transduction. Hair cell development and function are tightly regulated, and hair cell deficits are the main reasons for hearing loss and balance disorders. TMCC2 is an endoplasmic reticulum (ER)-residing transmembrane protein whose physiological function largely remains unknown. In the present work, we show that Tmcc2 is specifically expressed in the auditory hair cells of mouse inner ear. Tmcc2 knockout mice were then established to investigate its physiological role in hearing. Auditory brainstem responses measurements show that Tmcc2 knockout mice suffer from congenital hearing loss. Further investigations reveal progressive auditory hair cell loss in the Tmcc2 knockout mice. The general morphology and function of ER are unaffected in Tmcc2 knockout hair cells. However, increased ER stress was observed in Tmcc2 knockout mice and knockdown cells, suggesting that loss of TMCC2 leads to auditory hair cell death through elevated ER stress.

Orthopedic hip, knee, and spinal surgeries have a relatively high incidence of persistent postoperative pain, with the highest risk observed in Asian ethnicity. This study aimed to investigate the distribution of persistent pain at 1 year after surgery and its associated factors and effects on functional disability.This secondary analysis of a prospective observational study included 297 patients aged ≥ 55 years who underwent elective total hip arthroplasty, total knee arthroplasty, and spine and spinal cord surgeries under general anesthesia. Data were collected perioperatively and at 3 months and 1 year postoperatively to assess persistent postoperative pain on a numerical rating scale.At 1 year postoperatively, 34.6% (103/297) of patients reported pain, with a score of ≥ 1 and a mean score of 1.2. Multivariable negative binomial regression analysis revealed that less preoperative bodily pain (risk ratio [RR], 0.97; 95% confidence interval [CI] 0.94-0.99), preoperative C-reactive protein (CRP) level (RR, 1.19; 95% CI 1.01-1.39), and spine and spinal cord surgeries (RR, 2.48; 95% CI 1.30-4.75) increased the risk of persistent pain at 1 year after surgery, which was a significant factor for predicting the 12-item World Health Organization Disability Assessment Schedule 2.0 score (p 0.001).The mean score for persistent pain at 1 year after surgery on the numerical rating scale was 1.2. Worse preoperative bodily pain, higher preoperative serum CRP level, and spine and spinal cord surgeries increased the persistent pain score at 1 year after surgery, which was associated with functional disability CLINICAL TRIAL REGISTRATION: This prospective observational study was registered on the University Hospital Medical Information Network (31 December 2015; UMIN000021671).

Manageable thermal expansion (MTE) of metal trifluorides can be achieved by introducing local structure distortion (LSD) in the negative thermal expansion ScF

This study evaluated the effect of gossypol acetate, a potential antifertility compound, on semen quality and testicular histopathology of boars. Six boars were allotted into two experimental groups. Half of the animals were fed a diet that was supplemented with 2 mg of gossypol acetate per kg body weight per day for 9 weeks, control animals received a gossypol acetate-free feed. During the experimental period, semen was collected weekly from each boar and semen parameters were recorded. The animals were then euthanized, testicular samples were collected and histopathological examination of the testicular cells, as well as morphometrical analysis of the seminiferous tubules, were performed. The percentage of spermatozoa showing tail abnormalities increased significantly (P=0.017) in the semen of boars fed gossypol acetate-supplemented feed, while several other semen parameters deteriorated without showing statistical significance. Gossypol acetate supplementation also led to a decrease (P=0.042) in the number of spermatogonia in the seminiferous tubules and an increase (P=0.020) in the number of vacuoles in the seminiferous epithelium, consistent with changes seen in cases of male reproductive toxicity. In conclusion, gossypol acetate negatively affected a number of semen characteristics and also had detrimental effects on the histopathology of the testes.

Amyloid-β oligomers (AβOs) was the core-biomarker of Alzheimer's disease (AD), and the detection of AβOs is very important for the early diagnosis of AD. However, existing tests for AβOs are majorly suffering from complex process and poor sensitivity. Thus, an adjustable AβOs electrochemiluminescence (ECL) aptasensor based on the synergistic effect of self-enhanced metal-organic gel (AgCNS) and triple-helix DNA system (THS) was successfully constructed. AgCNS was prepared by an extremely simple one-pot method and was an innovative luminophore with excellent ECL performance. The AgCNS-labeled complementary sequence (AgCNS@CP) was interlaced with the unlabeled aptamer (Apt) carrying two short-arms fixed on the gold electrode (GE) to form the THS. Along with the specific-binding of AβOs and Apt, the THS was disrupted and adjusted flexibly between "on" and "off", resulting in significant changes in the ECL signals. Thus, ECL detection of AβOs was sensitively achieved with a detection limit as low as 0.23 fM and the different forms of Aβ can be specifically distinguished. The aptasensor also exhibited satisfactory selectivity, stability and reproducibility. Moreover, when proposed method and ELISA-kit were simultaneously applied to artificial cerebrospinal fluid (A-CSF) samples, the obtained results were completely consistent, reflecting the potential clinical application value of this work.

Mechanical impact-induced primary injury after traumatic brain injury (TBI) leads to acute microglial pro-inflammatory activation and consequently mediates neurodegeneration, which is a major secondary brain injury mechanism. However, the detailed pathologic cascades have not been fully elucidated, partially because of the pathologic complexity in animal TBI models. Although there are severalin vitroTBI models, none of them closely mimic post-TBI microglial activation. In the present study, we aimed to establish anin vitroTBI model, specifically reconstituting the pro-inflammatory activation and associated neurodegeneration following TBI. We proposed three sets of experiments. First, we established a needle scratch injured neuron-induced microglial activation and neurodegenerationin vitromodel of TBI. Second, we compared microglial pro-inflammatory cytokines profiles between thein vitroTBI model and TBI in male mice. Additionally, we validated the role of injured neurons-derived damage-associated molecular patterns in amplifying microglial pro-inflammatory pathways using thein vitroTBI model. Third, we applied thein vitromodel for the first time to characterize the cellular metabolic profile of needle scratch injured-neuron-activated microglia, and define the role of metabolic reprogramming in mediating pro-inflammatory microglial activation and mediated neurodegeneration. Our results showed that we successfully established a novelin vitroTBI model, which closely mimics primary neuronal injury-triggered microglial pro-inflammatory activation and mediated neurodegeneration after TBI. Thisin vitromodel provides an advanced and highly translational platform for dissecting interactions in the pathologic processes of neuronal injury-microglial activation-neuronal degeneration cascade, and elucidating the detailed underlying cellular and molecular insights after TBI.SIGNIFICANCE STATEMENTMicroglial activation is a key component of acute neuroinflammation that leads to neurodegeneration and long-term neurologic outcome deficits after TBI. However, it is not feasible to truly dissect primary neuronal injury-induced microglia activation, and consequently mediated neurodegenerationin vivo. Furthermore, there is currently lacking ofin vitroTBI models closely mimicking the TBI primary injury-mediated microglial activation. In this study, we successfully established and validated a novelin vitroTBI model of microglial activation, and for the first time, characterized the cellular metabolic profile of microglia in this model. This novel microglial activationin vitroTBI model will help in elucidating microglial inflammatory activation and consequently associated neurodegeneration after TBI.

The aim is to develop a radiomics model based on contrast-enhanced CT scans for preoperative prediction of perirenal fat invasion (PFI) in patients with renal cell carcinoma (RCC).The CT data of 131 patients with pathology-confirmed PFI status (64 positives) were retrospectively collected and randomly assigned to the training and test datasets. The kidneys and the masses were annotated by semi-automatic segmentation. Eight types of regions of interest (ROI) were chosen for the training of the radiomics models. The areas under the curves (AUCs) from the receiver operating characteristic (ROC) curve analysis were used to analyze the diagnostic performance. Eight types of models with different ROIs have been developed. The models with the highest AUC in the test dataset were used for construction of the corresponding final model, and comparison with radiologists' diagnosis.The AUCs of the models for each ROI was 0.783-0.926, and there was no statistically significant difference between them (P 0.05). Model 4 was using the ROI of the outer half-ring which extended along the edge of the mass at the outer edge of the kidney into the perirenal fat space with a thickness of 3 mm. It yielded the highest AUC (0.926) and its diagnostic accuracy was higher than the radiologists' diagnosis.We have developed and validated a radiomics model for prediction of PFI on RCC with contrast-enhanced CT scans. The model proved to be more accurate than the radiologists' diagnosis.

This study evaluated vault changes in eyes implanted with an implantable Collamer lens (ICL) with a central hole (ICL V4c) for myopia and astigmatism correction as well as factors related to vault changes over time.This retrospective study enrolled 169 myopic eyes from 169 patients (137 women and 32 men) who underwent ICL V4c implantation to correct myopia and astigmatism. Vault values were measured quantitatively using a rotating Scheimpflug camera. Each patient underwent at least four postoperative follow-up visits at 1 month, 6 months, 1 year, and more than 2 years. We compared postoperative values between groups and identified factors affecting vault changes over time.The mean vaults at 1 month (baseline), 6 months, 1 year, and the last follow-up time following ICL implantation were 540.83 ± 186.13, 520.00 ± 196.08, 503.79 ± 198.30, and 471.42 ± 211.35 μm, respectively. Eyes with baseline vaults of 250-750 and ≥ 750 μm exhibited a trend of vault decrease over time, and the differences were statistically significant (P 0.05) at 6 months and 1 year postoperatively, respectively. The variables relevant to the value of vault decrease between baseline and last follow-up time were anterior chamber depth (ACD) and ICL power (adjusted RWe found a trend of decreased mean objective vault values over time, which was more obvious in eyes with higher baseline vault values. The vault value of the ICL decreased more in eyes with shallower ACDs, higher ICL power, or both. Moreover, the decrease in vault values became statistically significant earlier in eyes with higher baseline vaults or shallower ACDs.

In China, the demand for implantable collamer lens (ICL) surgery is booming. Immediate sequential bilateral ICL surgery (ISBICLS) benefits patients and clinics, but it remains controversial and lacks standardization. We aim to investigate the prevalence of, factors for, and surgeon attitudes toward ISBICLS.In this cross-sectional survey study, an electronic questionnaire about the practice and attitudes toward performing ISBICLS or delayed sequential bilateral ICL surgery (DSBICLS) was distributed to 792 qualified ICL surgeons in Mainland China, between 4 April and 22 April 2022.A total of 531 surgeons (66.79%) from 30 provinces in Mainland China responded. Among them, 374 (67.23%) were currently performing ISBICLS. Fifty-two percent (277) of surgeons reported performing ISBICLS more than 50% of the time, while 85.05% of surgeons chose to perform the second eye surgery 1 day after the first eye surgery. Seventy percent (248) of surgeons performing ISBICLS chose to perform the second eye surgery less than 30 min after the first eye surgery. Surgeons who started ICL surgery earlier (before 2010, OR = 2.772, 95% CI = 1.290-5.957, P = 0.009; 2011-2013, OR = 2.479, 95% CI = 1.060-5.800, P = 0.036), completed one-eye ICL surgery faster ( 3 min, OR = 3.936, 95% CI = 1.505-10.293, P = 0.005) and modified the second eye ICL selection less frequently (1-25%, OR = 0.203, 95% CI = 0.054-0.771, P = 0.019; 26-50%, OR = 0.173, 95% CI = 0.041-0.726, P = 0.017; 51-75%, OR = 0.299, 95% CI = 0.041-0.726, P = 0.123; 76-100%, OR = 0.163, 95% CI = 0.039-0.688, P = 0.014) tended to perform ISBICLS. No significant association was found among clinical settings, preoperative measurement devices, and hospital policies with performing ISBICLS. Regarding their attitudes toward ISBICLS, 54.63% preferred ISBICLS and 45.37% preferred DSBICLS. The main supporting reasons were patient convenience (98.64%), faster vision rehabilitation (73.56%), and improved perioperative compliance (73.22%). The concerns regarding ISBICLS included the risk of endophthalmitis (62.22%), lack of recommendation in expert consensus (61.67%), and decreased vault predictability (60.93%). The most common desires for further adoption were expert consensus on surgical criteria and patient indicators for ISBICLS (82.3%).ISBICLS has been gradually adopted in Mainland China, but has not been widely accepted as a routine procedure. Surgeons' experience and skills mainly influence whether ISBICLS is performed. Further research is needed to explore standardized protocols to prevent endophthalmitis, the appropriate time interval of two eye surgery, and requisitions for surgeon skills.

The manufacture of In Vitro Fertilization (IVF) needles is subject to the most stringent quality demands. This makes automated inspection challenging due to difficulty in reliably classifying conforming and non-conforming (defective) products due to factors including multidimensional variation of their tip geometry and the lack of an explicit quality standard. In addition, developing an IVF needle image dataset, which broadly contains the visual characteristics of qualified and defective products, is difficult without commissioning large and costly production runs. The most important original contribution of this work is a new solution to investigate and quantify the uncertainty in the quality standard of IVF needles by integrating inter-disciplinary techniques. This work utilizes a low-cost, virtual dataset of synthetic images, generated by the automated photo-realistic rendering of a three-dimensional (3D) parametric model to simulate manufacturing variation. Then, the unknown numerical (critical) quality thresholds are obtained by estimating the relationship between quality response and measurement predictors using an Ordinal Logistic Regression (OLR) algorithm on the synthetic images. The fitted models exhibited increased overall predictive accuracy of up to 11.02% than the machine learning models (available in MATLAB) and could provide objective guidance on classifying specific quality aspects of a product.

Purpose Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT 9/L) patients undergoing elective invasive procedures. Methods In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 109/L that increased to ≥ 20 × 109/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. Results The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 109/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. Conclusions Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.

Preoperative observation of liver status in patients with liver tumors by abdominal Computed Tomography (CT) imaging is one of the essential references for formulating surgical plans. Preoperative vessel segmentation in the patient’s liver region has become an increasingly important and challenging problem. Almost all existing methods first segment arterial and venous vessels on CT in the arterial and venous phases, respectively. Then, the two are directly registered to complete the reconstruction of the vascular system, ignoring the displacement and deformation of blood vessels caused by changes in body position and respiration in the two phases. We propose an unsupervised domain-adaptive two-stage vessel segmentation framework for simultaneous fine segmentation of arterial and venous vessels on venous phase CT. Specifically, we first achieve domain adaptation for arterial and venous phase CT using a modified cycle-consistent adversarial network. The newly added discriminator can improve the ability to generate and discriminate tiny blood vessels, making the domain-adaptive network more robust. The second-stage supervised training of arterial vessels was then performed on the translated arterial phase CT. In this process, we propose an orthogonal depth projection loss function to enhance the representation ability of the 3D U-shape segmentation network for the geometric information of the vessel model. The segmented venous vessels were also performed on venous phase CT in the second stage. Finally, we invited professional doctors to annotate arterial and venous vessels on the venous phase CT of the test set. The experimental results show that the segmentation accuracy of arterial and venous vessels on venous phase CT is 0.8454 and 0.8087, respectively. Our proposed framework can simultaneously achieve supervised segmentation of venous vessels and unsupervised segmentation of arterial vessels on venous phase CT. Our approach can be extended to other fields of medical segmentation, such as unsupervised domain adaptive segmentation of liver tumors at different CT phases, to facilitate the development of the community.

In recent years, heavy metal pollution has become increasingly serious. Heavy metals exist in an environment mainly in the form of ions (heavy metal ions, HMs). They can contaminate food, water, soil, and the atmosphere, leading to serious harm to plants and animals. With high bioavailability and nonbiodegradability, HMs can accumulate through biomagnification. Consequently, heavy metal pollution has become the cause of many fatal diseases threatening human health and ecological environment. Therefore, the accurate detection of HMs is vital and necessary. In this paper, the harm and limit standards of heavy metals were systematically summarized and the common analysis methods were overviewed and compared. Specifically, the latest research progress of ratiometric photoelectric sensor, including optical and electrical sensor, were mainly described. The research status and advantages and disadvantages of a photoelectric sensor were summarized. Furthermore, the future directions were proposed, which provided the reference for the further research and application of the ratiometric photoelectric sensor.

Background Limited liver resections (LLRs) for tumours located in the posterosuperior segments of the liver are technically demanding procedures. This study compared outcomes of robotic (R) and laparoscopic (L) LLR for tumours located in the posterosuperior liver segments (IV, VII, and VIII). Methods This was an international multicentre retrospective analysis of patients who underwent R-LLR or L-LLR at 24 centres between 2010 and 2019. Patient demographics, perioperative parameters, and postoperative outcomes were analysed; 1 : 3 propensity score matching (PSM) and 1 : 1 coarsened exact matching (CEM) were performed. Results Of 1566 patients undergoing R-LLR and L-LLR, 983 met the study inclusion criteria. Before matching, 159 R-LLRs and 824 L-LLRs were included. After 1 : 3 PSM of 127 R-LLRs and 381 L-LLRs, comparison of perioperative outcomes showed that median blood loss (100 (i.q.r. 40–200) versus 200 (100–500) ml; P = 0.003), blood loss of at least 500 ml (9 (7.4 per cent) versus 94 (27.6 per cent); P < 0.001), intraoperative blood transfusion rate (4 (3.1 per cent) versus 38 (10.0 per cent); P = 0.025), rate of conversion to open surgery (1 (0.8 per cent) versus 30 (7.9 per cent); P = 0.022), median duration of Pringle manoeuvre when applied (30 (20–46) versus 40 (25–58) min; P = 0.012), and median duration of operation (175 (130–255) versus 224 (155–300); P < 0.001) were lower in the R-LLR group compared with the L-LLR group. After 1 : 1 CEM of 104 R-LLRs with 104 L-LLRs, R-LLR was similarly associated with significantly reduced blood loss and a lower rate of conversion to open surgery. Conclusion Based on a matched analysis of well selected patients, both robotic and laparoscopic access could be undertaken safely with good outcomes for tumours in the posterosuperior liver segments.

The purposes of this study are to explore the function and regulatory mechanism of a novel lncRNA MYC-Induced Long non-coding RNA (MINCR) in osteoarthritis (OA). The expression of lncRNA MINCR, miR-146a-5p, and bone morphogenetic protein receptor 2 (BMPR2), Sry-type high-mobility-group box 9 (SOX9), collagen type II alpha 1 (COL2A1), Aggrecan, metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), Matrix metalloproteinase 3 (MMP3), MMP13, COL2A1, and Aggrecan were determined using quantitative real-time PCR (qRT-PCR), western blot, immunohistochemistry (IHC) and immunofluorescence (IF)

Background. Artesunate (AS) is a derivative of artemisinin that can exert anti-inflammatory effects. This study aims to explore the effect of AS on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Methods. The newborn mice were used for experimental ARDS model establishment by intraperitoneal injection of LPS (10 mg/kg) into mice with or without AS (20 mg/kg) pretreatment. After that, the pathological morphology of mouse lung tissue was observed by H&E staining. The content of inflammatory factors in serum was measured by ELISA and mRNA expression and lung tissue was determined by qRT-PCR. The expression of NLRP3 inflammasome and related proteins in lung tissue was confirmed by immunohistochemistry and Western blot. Results. AS treatment effectively alleviated the LPS-induced lung injury and pulmonary edema, and reduced the expression of IL-1β, IL-18, IL-6, IL-8, MCP-1, and TNF-α in serum and lung tissues of experimental ARDS mice. In addition, AS treatment reduced the expression of NLRP3, ASC, and caspase-1 in lung tissues of experimental ARDS mice. Conclusion. AS alleviated LPS-induced lung injury in ARDS mice by inhibiting the activation of NLRP3 inflammasome.

It is urgent to identify the development of the Corona Virus Disease 2019 (COVID-19) in countries around the world. Therefore, visualization is particularly important for monitoring the COVID-19. In this paper, we visually analyze the real-time data of COVID-19, to monitor the trend of COVID-19 in the form of charts. At present, the COVID-19 is still spreading. However, in the existing works, the visualization of COVID-19 data has not established a certain connection between the forecast of the epidemic data and the forecast of the epidemic. To better predict the development trend of the COVID-19, we establish a logistic growth model to predict the development of the epidemic by using the same data source in the visualization. However, the logistic growth model only has a single feature. To predict the epidemic situation in an all-round way, we also predict the development trend of the COVID-19 based on the Susceptible Exposed Infected Removed epidemic model with multiple features. We fit the data predicted by the model to the real COVID-19 epidemic data. The simulation results show that the predicted epidemic development trend is consistent with the actual epidemic development trend, and our model performs well in predicting the trend of COVID-19.

Diabetes increases the risk of Alzheimer's disease (AD). We investigated the impact of glucose concentrations on the β-amyloid (Aβ)-induced alteration of mitochondrial/cellular energetics in primary human brain microvascular endothelial cells (HBMECs). HBMECs were grown and passaged in media containing 15 mmol/l glucose (normal) based on which the glucose levels in the media were designated as high (25 mmol/L) or low (5 mmol/L). HBMECs were treated with Aβ (1-42) (5 µmol/l) or a scrambled peptide for 24 h and mitochondrial respiratory parameters were measured using Seahorse Mito Stress Test. Aβ (1-42) decreased the mitochondrial ATP production at normal glucose levels and decreased spare respiratory capacity at high glucose levels. Aβ (1-42) diminished all mitochondrial respiratory parameters markedly at low glucose levels that were not completely recovered by restoring normal glucose levels in the media. The addition of mannitol (10 mmol/l) to low and normal glucose-containing media altered the Aβ (1-42)-induced bioenergetic defects. Even at normal glucose levels, pre-senescent HMBECs (passage 15) displayed greater Aβ (1-42)-induced mitochondrial respiratory impairments than young cells (passages 7-9). Thus, hypoglycemia, osmolarity changes, and senescence are stronger instigators of Aβ (1-42)-induced mitochondrial respiration and energetics in HBMECs and contributors to diabetes-related increased AD risk than hyperglycemia.

Intrahepatic cholangiocarcinoma (iCCA) exhibits extensive intratumoral heterogeneity and an extremely high mortality rate. Here, we performed whole-exome sequencing, RNA sequencing, T-cell receptor (TCR) sequencing, and multiplexed immunofluorescence on 207 tumor regions from 45 patients with iCCA. Over half of iCCA displayed intratumoral heterogeneity of immune infiltration, and iCCA were classified into sparsely, heterogeneously, and highly infiltrated subgroups with distinct immunogenomic characteristics. Sparsely infiltrated tumors displayed active copy-number loss of clonal neoantigens, and heterogeneous immune infiltration played an important role in the subclonal evolution across tumor subregions. Highly infiltrated tumors were characterized by extensive immune activation and a similar TCR repertoire across tumor subregions, but counteracted with T-cell exhaustion and pervasive antigen presentation defects. Notably, FGFR2 mutations and fusions correlated with low mutation burden and reduced immune infiltration. Our work delineated the dynamic tumor–immune interactions and developed a robust classification system to divide patients with iCCA into high and low immune evasion groups with different prognoses. Significance: This study elucidates the impact of spatial immune heterogeneity upon tumor evolution of iCCA and reveals distinct immune evasion mechanisms developed in different immune microenvironments, which can be exploited for the development of personalized immunotherapy strategies. This article is highlighted in the In This Issue feature, p. 2221

To analyze the factors related to corrected distance vision acuity (CDVA) after implantable collamer lens (ICL) implantation in patients with preoperative suboptimal CDVA.This retrospective study included patients with suboptimal preoperative CDVA (CDVA ≤ 20/25) who underwent ICL implantation (V4 or V4c). Preoperative and postoperative clinical evaluations included CDVA, uncorrected distance visual acuity (UDVA), and refraction.A total of 1212 eyes from 731 patients were identified. CDVA increased in 90.8% of the eyes after surgery. Among them, 57.5% of the eyes (697 eyes) gained more than one line. The preoperative LogMAR CDVA was 0.32 ± 0.23, which significantly improved to 0.13 ± 0.17 postoperatively (ICL implantation can improve CDVA in eyes with suboptimal CDVA. This study provides the postoperative outcomes of eyes with different preoperative CDVA, which makes it convenient for surgeons to communicate with such patients before surgery.