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Abstract Background Immune-positron emission tomography (PET) imaging with tracers that target CD8 and granzyme B has shown promise in predicting the therapeutic response following immune checkpoint blockade (ICB) in immunologically “hot” tumors. However, immune dynamics in the low T-cell infiltrating “cold” tumor immune microenvironment during ICB remain poorly understood. This study uses molecular imaging to evaluate changes in CD4 + T cells and CD8 + T cells during ICB in breast cancer models and examines biomarkers of response. Methods [89Zr]Zr-DFO-CD4 and [89Zr]Zr-DFO-CD8 radiotracers were used to quantify changes in intratumoral and splenic CD4 T cells and CD8 T cells in response to ICB treatment in 4T1 and MMTV-HER2 mouse models, which represent immunologically “cold” tumors. A correlation between PET quantification metrics and long-term anti-tumor response was observed. Further biological validation was obtained by autoradiography and immunofluorescence. Results Following ICB treatment, an increase in the CD8-specific PET signal was observed within 6 days, and an increase in the CD4-specific PET signal was observed within 2 days in tumors that eventually responded to immunotherapy, while no significant differences in CD4 or CD8 were found at the baseline of treatment that differentiated responders from nonresponders. Furthermore, mice whose tumors responded to ICB had a lower CD8 PET signal in the spleen and a higher CD4 PET signal in the spleen compared to non-responders. Intratumoral spatial heterogeneity of the CD8 and CD4-specific PET signals was lower in responders compared to non-responders. Finally, PET imaging, autoradiography, and immunofluorescence signals were correlated when comparing in vivo imaging to ex vivo validations. Conclusions CD4- and CD8-specific immuno-PET imaging can be used to characterize the in vivo distribution of CD4 + and CD8 + T cells in response to immune checkpoint blockade. Imaging metrics that describe the overall levels and distribution of CD8 + T cells and CD4 + T cells can provide insight into immunological alterations, predict biomarkers of response to immunotherapy, and guide clinical decision-making in those tumors where the kinetics of the response differ.

Abstract Introduction Chronic non-infectious uveitis affecting the posterior segment (NIU-PS), which can be recurrent and persistent for numerous years, mainly affects people of working age and significantly increases the risk of visual impairment. This study aimed to investigate the cost-effectiveness of fluocinolone acetonide intravitreal (FAI) implant in the treatment of patients with chronic NIU-PS from the Chinese healthcare perspective. Methods A Markov model with a 2-week cycle was constructed from the perspective of the Chinese healthcare system over a lifetime time horizon. The model consists of four health states: on-treatment, treatment failure, blindness, and death. The outcomes for effectiveness were based on the Chinese real-world study (RWS). Utilities and mortality rates were derived from published literature and standard sources. Costs were determined from the MENET website, prices of medical service items at local providers, published literature, and expert surveys. Outcomes were measured in quality-adjusted life years (QALYs). Sensitivity analyses were performed to account for the impact of uncertainty. Results It was estimated that in the base case, the FAI implant provided 0.43 incremental QALYs compared with the limited current practice (LCP) at an additional cost of $7503.72 (¥50,575.05), resulting in an incremental cost-effectiveness ratio (ICER) of $17,373.49 (¥117,097.33) per QALY gained. Parameters related to utility emerged as the primary influencers on the outcomes. In probabilistic sensitivity analysis (PSA), considering the willingness-to-pay (WTP) threshold of $19,072 (¥128,547) and $38,145 (¥257,094), the FAI implant had 67.70% and 99.50% probability of being cost-effective, respectively. As demonstrated in the scenario analysis, if the FAI implant aligns its price reduction with the average rate from the 2023 negotiation of the National Reimbursement Drug List (NRDL), it would result in lower costs and represent an absolute advantage. Conclusions The FAI implant, which can effectively reduce the recurrence rate and maintain the incremental costs within the WTP limit, is likely to be cost-effective in treating chronic NIU-PS in China.

Abstract Disposable bamboo chopsticks (DBCs) are difficult to recycle, which inevitably cause secondary pollution. Based on energy and environmental issues, we propose a facile strategy to fabricate floatable photocatalyst (fPC) coated onto DBCs, which can be flexibly used in water purification. The photocatalyst of titania and titanium carbide on bamboo (TiO2/TiC@b) was successfully constructed from TiC-Ti powders and DBCs using a coating technique followed heat treatment in carbon powder, and the fPC exhibited excellent photocatalytic activity under visible light irradation. The analysis results indicate that rutile TiO2 forms on TiC during heat treatment, achieving a low-density material with an average value of approximately 0.5233 g/cm3. The coatings of TiO2/TiC on the bamboo are firm and uniform, with a particle size of about 20–50 nm. XPS results show that a large amount of oxygen vacancies is generated, due to the reaction atmosphere of more carbon and less oxygen, further favoring to narrowing the band gap of TiO2. Furthermore, TiO2 formed on residual TiC would induce the formation of a heterojunction, which effectively inhibits the photogenerated electron–hole recombination via the charge transfer effect. Notably, the degradation of dye Rhodamine B (Rh.B) is 62.4% within 3 h, while a previous adsorption of 36.0% for 1 h. The excellent photocatalytic performance of TiO2/TiC@b can be attributed to the enhanced reaction at the water/air interface due to the reduced light loss in water, improved visible-light response, increased accessible area and charge transfer effect. Our findings show that the proposed strategy achieves a simple, low-cost, and mass-producible method to fabricate fPC onto the used DBCs, which is expected to applied in multiple fields, especially in waste recycling and water treatment.

Abstract Aims Myocardial ischaemia–reperfusion injury (MIRI) contributes to serious myocardial injury and even death. Long non‐coding RNAs (lncRNAs) have been reported to play pivotal roles in the occurrence and development of MIRI. Here, the detailed molecular mechanism of lncRNA SNHG1 in MIRI was explored. Methods and results A cell model of MIRI was established through hypoxia/reoxygenation (H/R) stimulation. Cell viability and pyroptosis were evaluated utilizing MTT, PI staining, and flow cytometry. Interleukin (IL)‐1β and IL‐18 secretion levels were examined by ELISA. The gene and protein expression were detected by RT‐qPCR and western blot, respectively. Dual luciferase reporter gene, RIP and ChIP assays were performed to analyse the molecular interactions. The results showed that lncRNA SNHG1 overexpression alleviated H/R‐induced HL‐1 cell pyroptosis (all P

Background: We created and validated a computed tomography (CT)-based radiomic model using both clinical factors and the radiomic signature for assessing the strangulation risk of acute intestinal obstruction. This would assist surgeons in accurately predicting intestinal ischemia and strangulation in patients with intestinal obstruction. Methods: We recruited 289 patients with acute intestinal obstruction admitted in the Affiliated Hospital of Qingdao University from January 2019 to February 2022. The patients were allocated to a training (n = 226) and validation cohort (n = 63). Radiomic features were collected from CT images, and the radiomic signature was extracted and used to calculate a radiomic score (Rad-score). A nomogram was constructed using the clinical features and the Rad-score, and the performance of the clinical, radiomics, and nomogram models was assessed in the two cohorts. Results: Six robust features were used to construct the radiomic signature. The nomogram incorporating hemoglobin levels, C-reactive protein levels, American Society of Anesthesiologists score, time of obstruction, CT image of mesenteric fluid (P < 0.05), and the signature demonstrated good predictive ability for intestinal ischemia in patients with acute intestinal obstruction, with areas under the curve of 0.892 (95% confidence interval, 0.837–0.947) and 0.781 (95% confidence interval, 0.619–0.944) for the training and validation sets, respectively. The decision curve analysis showed that this model outperformed the clinical and radiomic signature models. Conclusion: The radiomic nomogram may effectively predict intestinal ischemia in patients with acute intestinal disease and may assist clinical decision-making.

Abstract Background Presurgical computed tomography (CT)-guided localization is frequently employed to reduce the thoracotomy conversion rate, while increasing the rate of successful sublobar resection of ground glass nodules (GGNs) via video-assisted thoracoscopic surgery (VATS). In this study, we compared the clinical efficacies of presurgical CT-guided hook-wire and indocyanine green (IG)-based localization of GGNs. Methods Between January 2018 and December 2021, we recruited 86 patients who underwent CT-guided hook-wire or IG-based GGN localization before VATS resection in our hospital, and compared the clinical efficiency and safety of both techniques. Results A total of 38 patients with 39 GGNs were included in the hook-wire group, whereas 48 patients with 50 GGNs were included in the IG group. There were no significant disparities in the baseline data between the two groups of patients. According to our investigation, the technical success rates of CT-based hook-wire- and IG-based localization procedures were 97.4% and 100%, respectively (P = 1.000). Moreover, the significantly longer localization duration (15.3 ± 6.3 min vs. 11.2 ± 5.3 min, P = 0.002) and higher visual analog scale (4.5 ± 0.6 vs. 3.0 ± 0.5, P = 0.001) were observed in the hook-wire patients, than in the IG patients. Occurrence of pneumothorax was significantly higher in hook-wire patients (27.3% vs. 6.3%, P = 0.048). Lung hemorrhage seemed higher in hook-wire patients (28.9% vs. 12.5%, P = 0.057) but did not reach statistical significance. Lastly, the technical success rates of VATS sublobar resection were 97.4% and 100% in hook-wire and IG patients, respectively (P = 1.000). Conclusions Both hook-wire- and IG-based localization methods can effectively identified GGNs before VATS resection. Furthermore, IG-based localization resulted in fewer complications, lower pain scores, and a shorter duration of localization.

To investigate the alleviating effect and mechanism of the docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced liver injury in mice, the murine liver injury model was established by gavage of BPA (5 mg/kg) or co-administration of BPA and DHA-PS (50 mg/kg or 100 mg/kg) for 6 weeks. The results showed that after administration of 100 mg/kg DHA-PS, the liver index, serum levels of AST, ALT, TC, TG, NEFA, and LDL-C in mice were significantly decreased, while HDL-C was significantly increased. The LPS, IL-6, IL-1β, TNF-α, and MDA levels in liver tissues were effectively down-regulated, and IL-10, SOD, GSH-Px, and CAT levels were effectively up-regulated. The H&E and Oil Red O staining results showed that liver damage was notably repaired and lipid deposition was notably reduced after DHA-PS administration. Furthermore, metabolomics and immunohistochemical studies revealed that DHA-PS mainly regulates glycerophospholipid metabolism and the SIRT1-AMPK pathway to improve metabolic disorders of the liver caused by BPA. Therefore, DHA-PS could potentially alleviate BPA-induced murine liver injury through suppressing inflammation and oxidative stress, and modulating lipid metabolism disorders.

ObjectiveSevere cutaneous adverse reactions (SCARs) are rare but life-threatening, with antibiotics being the main cause. This retrospective study from a single center was designed to analyze the culprit drugs, clinical features and treatment outcomes of antibiotic-induced SCARs.MethodsWe analyzed cases of antibiotic-induced SCARs in a tertiary hospital in China between January 2013 and January 2024, including Steven-Johnson syndrome (SJS) or Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Descriptive analysis of the demographic characteristics, clinical manifestations, treatment and prognosis were carried out.ResultsAmong 354 cases of SCARs, 63 validated antibiotic-related cases were included. Cephalosporins (31.7%), penicillins (25.4%), and quinolones (19.0%) were the most common triggers for SCARs. Overall, liver (50.8%), lungs (31.7%), and kidneys (23.8%) were the most frequently affected organ in SCARs cases. Eight patients (28.6%) in the SJS/SJS-TEN overlap group and 8 patients (80.0%) in the TEN group received combination therapy of corticosteroids and IVIG. Patients with SCARs caused by penicillins or cephalosporins could receive alternative treatments such as lincomamides, quinolones, and tetracyclines. The mortality rate in the TEN group was the highest at 20.0%, followed by the SJS/SJS-TEN overlap group (7.1%), and no deaths were observed in the DRESS and AGEP groups.ConclusionThe identification of the culprit antibiotics and the application of alternative antibiotic therapies are crucial for the management of antibiotic-induced SCARs. If complicated underlying conditions and complications like advanced age, cancer and pneumonia coexist with SCARs, patients might be more at risk for mortality.

The silent information regulator sirtuin 1 (SIRT1) protein is an NAD+-dependent class-III lysine deacetylase that serves as an important post-transcriptional modifier targeting lysine acetylation sites to mediate deacetylation modifications of histones and non-histone proteins. SIRT1 has been reported to be involved in several physiological or pathological processes such as aging, inflammation, immune responses, oxidative stress and allergic diseases. In this review, we summarized the regulatory roles of SIRT1 during allergic disorder progression. Furthermore, we highlight the therapeutic effects of targeting SIRT1 in allergic diseases.

BackgroundEvidence for anorexia and bulimia in relation to the risk of ulcerative colitis (UC) is limited and inconsistent. The objective of this research was to utilize bi-directional, two-sample Mendelian randomization (MR) analysis to predict the causal association between anorexia nervosa and bulimia nervosa with UC.MethodsThe genome-wide association studies (GWAS) provided data for anorexia and bulimia from the UK Biobank, utilizing single-nucleotide polymorphisms (SNP) as instrumental variables. Additionally, genetic associations with UC were collected from various sources including the FinnGen Biobank, the UK Biobank and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The main analytical approach utilized in this study was the inverse-variance-weighted (IVW) method. To evaluate horizontal pleiotropy, the researchers conducted MR-Egger regression and MR-PRESSO global test analyses. Additionally, heterogeneity was assessed using the Cochran’s Q test.ResultsThis study found a negative association between genetically predicted bulimia (OR = 0.943, 95% CI: 0.893–0.996; p = 0.034) and the risk of UC in the IIBDGC dataset, indicating that individuals with bulimia have approximately a 5.7% lower risk of developing UC. No association was observed in the other two datasets. Conversely, genetically predicted anorexia was not found to be causally associated with UC. In bi-directional Mendelian randomization, UC from the IIBDGC dataset was negatively associated with the risk of anorexia (OR = 0.877, 95% CI: 0.797–0.965; p = 0.007), suggesting that UC patients have approximately a 12.3% lower risk of developing anorexia, but not causally associated with bulimia.ConclusionGenetically predicted bulimia may have a negative association with the onset of UC, while genetically predicted anorexia does not show a causal relationship with the development of UC. Conversely, genetically predicted UC may have a negative association with the development of anorexia.

As the most common degenerative joint disease, osteoarthritis (OA) contributes significantly to pain and disability during aging. Several genes of interest involved in articular cartilage damage in OA have been identified. However, the direct causes of OA are poorly understood. Evaluating the public human RNA-seq dataset showed that CBFB (subunit of a heterodimeric Cbfβ/Runx1, Runx2, or Runx3 complex) expression is decreased in the cartilage of patients with OA. Here, we found that the chondrocyte-specific deletion of Cbfb in tamoxifen-induced Cbfbf/f;Col2a1-CreERT mice caused a spontaneous OA phenotype, worn articular cartilage, increased inflammation, and osteophytes. RNA-sequencing analysis showed that Cbfβ deficiency in articular cartilage resulted in reduced cartilage regeneration, increased canonical Wnt signaling and inflammatory response, and decreased Hippo/Yap signaling and Tgfβ signaling. Immunostaining and western blot validated these RNA-seq analysis results. ACLT surgery-induced OA decreased Cbfβ and Yap expression and increased active β-catenin expression in articular cartilage, while local AAV-mediated Cbfb overexpression promoted Yap expression and diminished active β-catenin expression in OA lesions. Remarkably, AAV-mediated Cbfb overexpression in knee joints of mice with OA showed the significant protective effect of Cbfβ on articular cartilage in the ACLT OA mouse model. Overall, this study, using loss-of-function and gain-of-function approaches, uncovered that low expression of Cbfβ may be the cause of OA. Moreover, Local admission of Cbfb may rescue and protect OA through decreasing Wnt/β-catenin signaling, and increasing Hippo/Yap signaling and Tgfβ/Smad2/3 signaling in OA articular cartilage, indicating that local Cbfb overexpression could be an effective strategy for treatment of OA.

Abstract A significant minority of individuals develop trauma- and stressor-related disorders (TSRD) after surviving sepsis, a life-threatening immune response to infections. Accurate prediction of risk for TSRD can facilitate targeted early intervention strategies, but many existing models rely on research measures that are impractical to incorporate to standard emergency department workflows. To increase the feasibility of implementation, we developed models that predict TSRD in the year after survival from sepsis using only electronic health records from the hospitalization (n = 217,122 hospitalizations from 2012-2015). The optimal model was evaluated in a temporally independent prospective test sample (n = 128,783 hospitalizations from 2016-2017), where patients in the highest-risk decile accounted for nearly one-third of TSRD cases. Our approach demonstrates that risk for TSRD after sepsis can be stratified without additional assessment burden on clinicians and patients, which increases the likelihood of model implementation in hospital settings.

Pregabalin is the first-line treatment for neuropathic pain. Cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. A 72-year-old man with severe herpes zoster neuralgia developed maculopapular drug eruption covering 80% to 90% of his total body surface area after 40 days of combined multidrug analgesia. A drug provocation test for pregabalin was positive. The time interval between initiating medication and the onset of the patient’s rash was the longest and he also had the largest area of skin affected compared with patients with a similar condition in previous related reports. Remaining vigilant for possible adverse cutaneous hypersensitivity reactions during treatment is important because of the long-term course of pregabalin treatment for neuropathic pain.

BackgroundPostoperative complications in adhesive small bowel obstruction (ASBO) significantly escalate healthcare costs and prolong hospital stays. This study endeavors to construct a nomogram that synergizes computed tomography (CT) body composition data with inflammatory-nutritional markers to forecast postoperative complications in ASBO.MethodsThe study’s internal cohort consisted of 190 ASBO patients recruited from October 2017 to November 2021, subsequently partitioned into training (n = 133) and internal validation (n = 57) groups at a 7:3 ratio. An additional external cohort comprised 52 patients. Body composition assessments were conducted at the third lumbar vertebral level utilizing CT images. Baseline characteristics alongside systemic inflammatory responses were meticulously documented. Through univariable and multivariable regression analyses, risk factors pertinent to postoperative complications were identified, culminating in the creation of a predictive nomogram. The nomogram’s precision was appraised using the concordance index (C-index) and the area under the receiver operating characteristic (ROC) curve.ResultsPostoperative complications were observed in 65 (48.87%), 26 (45.61%), and 22 (42.31%) patients across the three cohorts, respectively. Multivariate analysis revealed that nutrition risk score (NRS), intestinal strangulation, skeletal muscle index (SMI), subcutaneous fat index (SFI), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR) were independently predictive of postoperative complications. These preoperative indicators were integral to the nomogram’s formulation. The model, amalgamating body composition and inflammatory-nutritional indices, demonstrated superior performance: the internal training set exhibited a 0.878 AUC (95% CI, 0.802–0.954), 0.755 accuracy, and 0.625 sensitivity; the internal validation set displayed a 0.831 AUC (95% CI, 0.675–0.986), 0.818 accuracy, and 0.812 sensitivity. In the external cohort, the model yielded an AUC of 0.886 (95% CI, 0.799–0.974), 0.808 accuracy, and 0.909 sensitivity. Calibration curves affirmed a strong concordance between predicted outcomes and actual events. Decision curve analysis substantiated that the model could confer benefits on patients with ASBO.ConclusionA rigorously developed and validated nomogram that incorporates body composition and inflammatory-nutritional indices proves to be a valuable tool for anticipating postoperative complications in ASBO patients, thus facilitating enhanced clinical decision-making.

BackgroundIruplinalkib is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) with efficacy in patients with ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC), which is independently developed by a Chinese pharmaceutical company. This study examined the cost-effectiveness of iruplinalkib versus alectinib in the Chinese healthcare setting.MethodsA partitioned survival model was developed to project the economic and health outcomes. Efficacy was derived using unanchored matching-adjusted indirect comparison (MAIC). Cost and utility values were obtained from the literature and experts’ opinions. Deterministic and probabilistic sensitivity analyses (PSA) were carried out to evaluate the model’s robustness.ResultsTreatment with iruplinalkib versus alectinib resulted in a gain of 0.843 quality-adjusted life years (QALYs) with incremental costs of $20,493.27, resulting in an incremental cost-effectiveness ratio (ICER) of $24,313.95/QALY. Parameters related to relative efficacy and drug costs were the main drivers of the model outcomes. From the PSA, iruplinalkib had a 90% probability of being cost-effective at a willingness-to-pay threshold of $37,863.56/QALY.ConclusionCompared to alectinib, iruplinalkib is a cost-effective therapy for patients with ALK-positive crizotinib-resistant advanced NSCLC.

Summary: Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

IntroductionMycobacterium tuberculosis (Mtb), the main cause of tuberculosis (TB), has brought a great burden to the world's public health. With the widespread use of Mtb drug-resistant strains, the pressure on anti-TB treatment is increasing. Anti-TB drugs with novel structures and targets are urgently needed. Previous studies have revealed a series of CYPs with important roles in the survival and metabolism of Mtb. However, there is little research on the structure and function of CYP138.MethodsIn our study, to discover the function and targetability of CYP138, a cyp138-knockout strain was built, and the function of CYP138 was speculated by the comparison between cyp138-knockout and wild-type strains through growth curves, growth status under different carbon sources, infection curves, SEM, MIC tests, quantitative proteomics, and lipidomics.Results and discussionThe knockout of cyp138 was proven to affect the Mtb's macrophage infection, antibiotics susceptibility, and the levels of fatty acid metabolism, membrane-related proteins, and lipids such as triacylglycerol. We proposed that CYP138 plays an important role in the synthesis and decomposition of lipids related to the cell membrane structure as a new potential anti-tuberculosis drug target.

Introduction: The objective of this study is to systematically evaluate the effect of ligustrazine on animal models of ischemic stroke and investigate its mechanism of action.Materials and Methods: The intervention of ligustrazine in ischemic diseases research on stroke model animals was searched in the Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP Database (VIP), Chinese Biomedical Literature Database (CBM), Cochrane Library, PubMed, Web of Science, and Embase databases. The quality of the included literature was evaluated using the Cochrane risk of bias tool. The evaluation included measures such as neurological deficit score (NDS), percentage of cerebral infarction volume, brain water content, inflammation-related factors, oxidative stress-related indicators, apoptosis indicators (caspase-3), and blood-brain barrier (BBB) permeability (Claudin-5).Results: A total of 32 studies were included in the analysis. The results indicated that ligustrazine significantly improved the neurological function scores of ischemic stroke animals compared to the control group (SMD = −1.84, 95% CI −2.14 to −1.55, P < 0.00001). It also reduced the percentage of cerebral infarction (SMD = −2.97, 95% CI −3.58 to −2.36, P < 0.00001) and brain water content (SMD = −2.37, 95% CI −3.63 to −1.12, P = 0.0002). In addition, ligustrazine can significantly improve various inflammatory factors such as TNF-α (SMD = −7.53, 95% CI −11.34 to −3.72, P = 0.0001), IL-1β (SMD = −2.65, 95% CI −3.87 to −1.44, P < 0.0001), and IL-6 (SMD = −5.55, 95% CI −9.32 to −1.78, P = 0.004). It also positively affects oxidative stress-related indicators including SOD (SMD = 4.60, 95% CI 2.10 to 7.10, P = 0.0003), NOS (SMD = −1.52, 95% CI −2.98 to −0.06, P = 0.04), MDA (SMD = −5.31, 95% CI −8.48 to −2.14, P = 0.001), and NO (SMD = −5.33, 95% CI −8.82 to −1.84, P = 0.003). Furthermore, it shows positive effects on the apoptosis indicator caspase-3 (SMD = −5.21, 95% CI −7.47 to −2.94, P < 0.00001) and the expression level of the sex-related protein Claudin-5, which influences BBB permeability (SMD = 7.38, 95% CI 3.95 to 10.82, P < 0.0001).Conclusion: Ligustrazine has been shown to have a protective effect in animal models of cerebral ischemic injury. Its mechanism of action is believed to be associated with the reduction of inflammation and oxidative stress, the inhibition of apoptosis, and the repair of BBB permeability. However, further high-quality animal experiments are required to validate these findings.

PurposeThe Diagnosis-Related Group (DRG) or Diagnosis-Intervention Packet (DIP) payment system, now introduced in China, intends to streamline healthcare billing practices. However, its implications for clinical pharmacists, pivotal stakeholders in the healthcare system, remain inadequately explored. This study sought to assess the perceptions, challenges, and roles of clinical pharmacists in China following the introduction of the DRG or DIP payment system.MethodsQualitative interviews were conducted among a sample of clinical pharmacists. Ten semi-structured interviews were conducted, either online or face to face. Thematic analysis was employed to identify key insights and concerns related to their professional landscape under the DRG or DIP system.ResultsClinical pharmacists exhibited variable awareness levels about the DRG or DIP system. Their roles have undergone shifts, creating a balance between traditional responsibilities and new obligations dictated by the DRG or DIP system. Professional development, particularly concerning health economics and DRG-based or DIP-based patient care, was highlighted as a key need. There were calls for policy support at both healthcare and national levels and a revised, holistic performance assessment system. The demand for more resources, be it in training platforms or personnel, was a recurrent theme.ConclusionThe DRG or DIP system’s introduction in China poses both opportunities and challenges for clinical pharmacists. Addressing awareness gaps, offering robust policy support, ensuring adequate resource allocation, and recognizing the evolving role of pharmacists are crucial for harmoniously integrating the DRG or DIP system into the Chinese healthcare paradigm.

Abstract Background Hypoxia is a frequent characteristic observed in solid tumors and is strongly associated with tumor metastasis, angiogenesis, and drug resistance. While the vasculature of hypoxic tumor tissues poses obstacles to the efficient administration of conventional drugs, it may prove advantageous in sustaining hyperthermia. Photothermal therapy (PTT) offers a promising treatment strategy that utilizes the activation of photosensitizers to produce heat, thus facilitating the selective ablation of tumor tissues. Method To enhance the accumulation of photothermal agents in tumor tissue and improve the effectiveness of PTT, we developed a self-propelled hybrid called Bif@PAu-NPs. This hybrid consists of polydopamine (PDA)-coated gold nanoparticles (Au-NPs) loaded onto the anaerobic Bifidobacterium infantis (Bif). Results The Bif@PAu-NPs actively aggregated at the tumor site because the ability of Bif can target hypoxic regions, and PAu-NPs achieved precise PTT due to their high photothermal conversion efficiency (η = 67.8%). The tumor tissues were ablated by PTT, resulting in the release of antigens through immunogenic cell death (ICD), which stimulates an immune response. The inclusion of GM-CSF enhanced the immune response by recruiting dendritic cells and initiating long-term anti-tumor immunity. Conclusion The Bif@PAu-NPs hybrid effectively suppressed the growth of both primary tumors and re-challenged tumors. The utilization Bif@PAu-NPs in conjunction with GM-SCF exhibits great potential as a photothermal-immunotherapeutic strategy for precisely treating solid tumors. Graphical Abstract In this study, the bacterial Bif@PAu-NPs biohybrid is exploited the self-driving ability of anaerobic Bifidobacterium infantis to deliver polydopamine-modified gold nanoparticles to hypoxic region of tumor. Under irradiation with 808 nm NIR laser, the hybrid exerts precise photothermal therapy to stimulate the immune response, which is further enhanced by GM-CSF, leading to recruitment of dendritic cells and initiation of a long-term anti-tumor immunity remember to prevent tumor recurrence.

Abstract Background Enhanced recovery after surgery (ERAS) protocols are widely used worldwide. Recently, studies of the ERAS program in spinal surgery subspecialties have been reported. The aim of this study was to evaluate the impacts of ERAS in minimally invasive microdiscectomy (MD) surgery. Methods This was a retrospective cohort study of patients undergoing MD at a single center. From March 2018 to March 2021, 286 patients were in the ERAS group. A total of 140 patients from March 2017 to February 2018 were in the conventional group. The outcomes included length of stay (LOS), the postoperative numeric rating scale (NRS), complications, 30-day readmission rate, 30-day reoperation rate and cost. Moreover, perioperative factors were also evaluated. Results Compared with the conventional group, the LOS and cost were reduced in the ERAS group. There were no significant differences in the NRS, complication rate, 30-day readmission or reoperation rates between the groups. Furthermore, postoperative drainage volume, and postoperative opioid use were lower in the ERAS group. Conclusions The ERAS protocol for MD surgery reduces LOS, cost and opioid use and accelerates patient recovery.

Abstract The band gap of rutile TiO2 has been narrowed, via the formation of oxygen vacancies (OVs) during heat treatment in carbon powder (cHT) with embedding TiO2 coatings. The narrowed band gap efficiently improves the visible light response of TiO2 coatings, to further enhance the visible-light-driven photocatalytic activity. The change in OVs during cHT has been studied by manipulation of cHT temperature and time. The effect of OVs on the band structure of nonstoichiometric TiO2-x has been further calculated by first-principles calculations. With raising the temperature, SEM images show that the nano-size fiber-like structure forms on the surface of TiO2 coatings, and the amount of the fiber-like structure significantly increases and their size changes from nano to micro under 800 °C, contributing to cause an increase in accessible surface area. The UV–Vis results reveal that the band gap of TiO2 has been narrowed during cHT, due to the formed oxygen vacancies. The XPS results further confirm that the formation of surface defects including OVs, and the XPS depth profile further shows the decreased relative amount of O whereas increased relative amount of carbon. Notably, after cHT for TiO2 coatings, the photocatalytic activity first increases then decreases with raising the temperature, achieving approximately 3 times at 850 °C. The first-principles calculation suggest that the OVs in TiO2 coatings with localized electrons could facilitate the band gap narrowing, further favoring to enhance the photocatalytic activity under visible light.

Wood exhibits a limited elastic deformation capacity under external forces due to its small range of elastic limit, which restricts its widespread use as an elastic material. This study presents the development of a stretchable wood-based elastomer (SWE) that is highly mechanical and flexible, achieved without the use of chemical cross-linking. Balsa wood was utilized as a raw material, which was chemically pretreated to remove the majority of the lignin and create a more abundant pore structure, while exposing the active hydroxyl groups on the cellulose surface. The polyvinyl alcohol (PVA) solution was impregnated into delignified wood, resulting in the formation of a cross-linked structure through multiple freeze–thaw cycles. After eight cycles, the tensile strength in the longitudinal direction reached up to 25.68 MPa with a strain of ~463%. This excellent mechanical strength is superior to that of most wood-based elastomers reported to date. The SWE can also perform complex deformations such as winding and knotting, and SWE soaked in salt solution exhibits excellent sensing characteristics and can be used to detect human finger bending. Stretchable wood-based elastomers with high mechanical strength and toughness have potential future applications in biomedicine, flexible electronics, and other fields.

Disabled older adults exhibited a higher risk for cognitive impairment. Early identification is crucial in alleviating the disease burden. This study aims to develop and validate a prediction model for identifying cognitive impairment among disabled older adults. A total of 2138, 501, and 746 participants were included in the development set and two external validation sets. Logistic regression, support vector machine, random forest, and XGBoost were introduced to develop the prediction model. A nomogram was further established to demonstrate the prediction model directly and vividly. Logistic regression exhibited better predictive performance on the test set with an area under the curve of 0.875. It maintained a high level of precision (0.808), specification (0.788), sensitivity (0.770), and F1-score (0.788) compared with the machine learning models. We further simplified and established a nomogram based on the logistic regression, comprising five variables: age, daily living activities, instrumental activity of daily living, hearing impairment, and visual impairment. The areas under the curve of the nomogram were 0.871, 0.825, and 0.863 in the internal and two external validation sets, respectively. This nomogram effectively identifies the risk of cognitive impairment in disabled older adults.

Breast cancer is characterized by insidious onset, rapid progression, easy recurrence, and metastasis. Conventional monotherapies are usually ineffective due to insufficient drug delivery. Therefore, the combination of multimodal therapy with tumor microenvironment (TME)-responsive nanoplatforms is increasingly being considered for the targeted treatment of breast cancer. We synthesized bioactive hybrid nanoparticles for synergistic chemotherapy and photothermal therapy. Briefly, doxorubicin (DOX) and indocyanine green (ICG)-loaded nanoparticles (DI) of average particle size 113.58 ± 2.14 nm were synthesized, and their surface were modified with polydopamine (PDA) and attached to the anaerobic probiotic Bifidobacterium infantis (Bif). The bioactive Bif@DIP hybrid showed good photothermal conversion efficiency of about 38.04%. In addition, the self-driving ability of Bif allowed targeted delivery of the PDA-coated DI nanoparticles (DIP) to the hypoxic regions of the tumor. The low pH and high GSH levels in the TME stimulated the controlled release of DOX and ICG from the Bif@DIP hybrid, which then triggered apoptosis of tumor cells and induced immunogenic cell death (ICD), resulting in effective and sustained anti-tumor effect with minimum systemic toxicity. Thus, the self-driven Bif@DIP hybrid is a promising nanodrug for the targeted chemotherapy and photothermal therapy against solid cancers.

Among various bio-inspired structures, sutures are a prominent structure which has evolved independently to optimize their functionalities. The diabolical ironclad beetle suture-inspired structure was fabricated using multi-material additive manufacturing (3D printing) system with TangoBlackPlus (TBP) as the soft suture layer and VeroWhitePlus (VWP) as the hard material. The print quality of the specimen was assessed through the optical microscope images, and a nanoindentation test was performed to investigate the interfacial hardness between TBP and VWP. Flexural properties of the suture structure when changing the thickness of the soft layers were then studied. Experiments were continued to identify the effect of combining different sizes of suture modules to develop the suture structure. A numerical simulation model was then generated and validated using the experimental results to proceed with the parametric study. A design of experiment (DoE) was developed to analyse the effect of changing the suture geometry to optimize performance. The research concluded that gradually decreasing the size of the suture allowed the structure to withstand higher loads. It was also evident that the deformability of the structure could be increased by incorporating smaller interlocking angles and larger a:b ratios, while larger interlocking angles and smaller a:b ratios generate stiff structures.

Introduction Compensatory mouth breathing, caused by nasopharyngeal obstructive diseases, is the main cause of hyperdivergent mandibular retrognathia in children. Such deformities require effective growth guidance before pubertal growth peaks. The traditional mandibular advancement device, twin block (TB), can guide the forward development of the mandible. However, the side effect of increasing the vertical dimension of the lower facial third, worsens the facial profile of children with divergent growth trends. To solve this problem, a modified TB (LLTB) appliance was designed to control the vertical dimension by intruding incisors and inhibiting the elongation of posterior teeth during the advancement of the mandible, which could avoid the side effects of traditional appliances and effectively guide the growth of the mandible in a normal direction.Methods and analysis The study was designed as a single-centre, single-blind, randomised, parallel controlled trial. We aim to enrol 60 children aged 9–14 years with hyperdivergent skeletal class II malocclusion, using a 1:1 allocation ratio. The participants were will be randomly assigned to receive either the TB or LLTB treatment. The primary outcome will be a change in the angle of the mandibular plane relative to the anterior cranial base. The secondary outcomes will include changes in the sagittal maxillomandibular relation, occlusal plane, facial height, morphology of the mandible and upper airway width. Safety endpoints will also be evaluated.Ethics and dissemination Ethical approval was obtained from the ethics committee of Shanghai Stomatological Hospital. Both participants and their guardians will be fully informed of the study and sign an informed consent form before participating in the trial. The results will be publicly available in peer-reviewed scientific journals.Trial registration number ChiCTR2000035882.

Revealing system behavior from observed time series is a fundamental problem worthy of in-depth study and exploration, and has attracted extensive attention in a wide range of fields due to its wide application values. In this paper, we propose a novel network construction method for time series analysis, which is different from the existing ordinal network method concerning the transition probability of ordinal patterns in transition networks. The proposed network representation is based on the combinatorial property concerning the inversion number of ordinal patterns from the ordinal partitions of time series. For the proposed network construction method, the network nodes are represented by each ordinal partition of time series and the edge weight between network nodes is determined by a novel proximity relationship of ordinal patterns which is a newly defined metric based on the inversion number of ordinal patterns. Using random signals and chaotic signals as examples, we demonstrate the potential of the proposed network construction method for the network representation of time series. We also employ the proposed network construction method in quantitative EEG for the identification of three different physiological and pathological brain states. According to the results of AUC values, one can observe that the discriminating power of the AND of the proposed network construction method is slightly stronger than that of the available ordinal network. The experimental results illustrate that our proposed network construction method opens up a new pathway for network representation of time series, which is capable of quantifying time series for feature extraction and pattern learning for time series analysis.

BackgroundFlavonoids are a class of plant chemicals known to have health-promoting properties, including six subclasses. Anthocyanin is one of the subclasses that have anti-inflammatory and antioxidant activities. However, the relationship between flavonoid subclass intake and the risk of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis has not been verified in representative samples of the United States.MethodsThis is a cross-sectional study based on the data from the National Health and Nutrition Examination Survey (NHANES) and the Food and Nutrient Database for Dietary Studies (FNDDS) in 2017–2018. The intake of flavonoid subclasses of the participants was obtained from two 24 h dietary recalls. The NAFLD and liver fibrosis were defined based on the international consensus criteria. The relationship between flavonoid subclass intake and NAFLD and liver fibrosis was evaluated using a multivariate logistic regression model corrected for multiple confounding factors. Subgroup analysis, trend tests, interaction tests and restricted cubic spline were carried out to further explore this relationship. In addition, we also explored the relationship between anthocyanin and liver serum biomarkers, dietary total energy intake and healthy eating index (HEI)-2015 scores.ResultsA total of 2,288 participants were included in the analysis. The intake of anthocyanin was significantly negatively associated with the risk of NAFLD, but not other flavonoid subclasses. A higher anthocyanin intake was significantly associated with a lower risk of NAFLD (quartile 4, OR 0.470, 95% CI 0.275–0.803). The results of subgroup analysis showed that the protective effect of dietary anthocyanin intake on NAFLD was more pronounced in participants of non-Hispanic whites, with hypertension and without diabetes (P for interaction

Abstract Objectives This study aims to develop and validate a virtual biopsy model to predict microsatellite instability (MSI) status in preoperative gastric cancer (GC) patients based on clinical information and the radiomics of deep learning algorithms. Methods A total of 223 GC patients with MSI status detected by postoperative immunohistochemical staining (IHC) were retrospectively recruited and randomly assigned to the training (n = 167) and testing (n = 56) sets in a 3:1 ratio. In the training set, 982 high-throughput radiomic features were extracted from preoperative abdominal dynamic contrast-enhanced CT (CECT) and screened. According to the deep learning multilayer perceptron (MLP), 15 optimal features were optimized to establish the radiomic feature score (Rad-score), and LASSO regression was used to screen out clinically independent predictors. Based on logistic regression, the Rad-score and clinically independent predictors were integrated to build the clinical radiomics model and visualized as a nomogram and independently verified in the testing set. The performance and clinical applicability of hybrid model in identifying MSI status were evaluated by the area under the receiver operating characteristic (AUC) curve, calibration curve, and decision curve (DCA). Results The AUCs of the clinical image model in training set and testing set were 0.883 [95% CI: 0.822–0.945] and 0.802 [95% CI: 0.666–0.937], respectively. This hybrid model showed good consistency in the calibration curve and clinical applicability in the DCA curve, respectively. Conclusions Using preoperative imaging and clinical information, we developed a deep-learning-based radiomics model for the non-invasive evaluation of MSI in GC patients. This model maybe can potentially support clinical treatment decision making for GC patients. Graphical abstract

Abstract Background Clinical tissue adhesives remain some critical drawbacks for managing emergency injuries, such as inadequate adhesive strength and insufficient anti-infection ability. Herein, a novel, self-healing, and antibacterial carboxymethyl chitosan/polyaldehyde dextran (CMCS/PD) hydrogel is designed as the first-aid tissue adhesive for effective trauma emergency management. Methods We examined the gel-forming time, porosity, self-healing, antibacterial properties, cytotoxicity, adhesive strength, and hemocompatibility. Liver hemorrhage, tail severance, and skin wound infection models of rats are constructed in vivo, respectively. Results Results demonstrate that the CMCS/PD hydrogel has the rapid gel-forming (~ 5 s), good self-healing, and effective antibacterial abilities, and could adhere to tissue firmly (adhesive strength of ~ 10 kPa and burst pressure of 327.5 mmHg) with excellent hemocompatibility and cytocompatibility. This suggests the great prospect of CMCS/PD hydrogel in acting as a first-aid tissue adhesive for trauma emergency management. The CMCS/PD hydrogel is observed to not only achieve rapid hemostasis for curing liver hemorrhage and tail severance in comparison to commercial hemostatic gel (Surgiflo ®) but also exhibit superior anti-infection for treating acute skin trauma compared with clinical disinfectant gel (Prontosan ®). Conclusions Overall, the CMCS/PD hydrogel offers a promising candidate for first-aid tissue adhesives to manage the trauma emergency. Because of the rapid gel-forming time, it could also be applied as a liquid first-aid bandage for mini-invasive surgical treatment. Graphical Abstract

Abstract Periodontitis, an infectious and common disease worldwide, leads to the destruction of the periodontal ligament-alveolar bone complex. Within the bone metabolic niche, communication between periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMMSCs) has been considered a major contributor to osteogenesis. PDLSC-derived extracellular vesicles (P-EVs) have shown great potential for bone regeneration. However, the secretion and uptake mechanisms of P-EVs remain elusive. Herein, the biogenesis of extracellular vesicles (EVs) from PDLSCs was observed using scanning and transmission electron microscopy. PDLSCs were transduced with Ras-associated protein 27a (Rab27a) siRNA (PDLSC siRab27a ) to inhibit EV secretion. The effect of P-EVs on BMMSCs was evaluated using a non-contact transwell co-culture system. We observed that Rab27a knockdown decreased EV secretion, and PDLSC siRab27a remarkably attenuated co-culture-enhanced osteogenesis of BMMSCs. Isolated PDLSC-derived EVs enhanced osteogenic differentiation of BMMSCs in vitro and induced bone regeneration in a calvarial defect model in vivo. PDLSC-derived EVs were rapidly endocytosed by BMMSCs via the lipid raft/cholesterol endocytosis pathway and triggered the phosphorylation of extracellular signal-regulated kinase 1/2. In conclusion, PDLSCs contribute to the osteogenesis of BMMSCs through Rab27a-mediated EV secretion, thereby providing a potential cell-free approach for bone regeneration.

The construction of complex networks from electroencephalography (EEG) proves to be an effective method for representing emotion patterns in affection computing as it offers rich spatiotemporal EEG features associated with brain emotions. In this paper, we propose a novel method for constructing complex networks from EEG signals for emotion recognition, which begins with phase space reconstruction to obtain ordinal patterns and subsequently forms a graph network representation from the sequence of ordinal patterns based on the visibility graph method, named ComNet-PSR-VG. For the proposed ComNet-PSR-VG, the initial step involves mapping EEG signals into a series of ordinal partitions using phase space reconstruction, generating a sequence of ordinal patterns. These ordinal patterns are then quantified to form a symbolized new sequence. Subsequently, the resulting symbolized sequence of ordinal patterns is transformed into a graph network using the visibility graph method. Two types of network node measures, average node degree (AND) and node degree entropy (NDE), are extracted from the graph networks as the inputs of machine learning for EEG emotion recognition. To evaluate the effectiveness of the proposed construction method of complex networks based on the visibility graph of ordinal patterns, comparative experiments are conducted using two types of simulated signals (random and Lorenz signals). Subsequently, EEG emotion recognition is performed on the SEED EEG emotion dataset. The experimental results show that, with AND as the feature, our proposed method is 4.88% higher than the existing visibility graph method and 12.23% higher than the phase space reconstruction method. These findings indicate that our proposed novel method for constructing complex networks from EEG signals not only achieves effective emotional EEG pattern recognition but also exhibits the potential for extension to other EEG pattern learning tasks, suggesting broad adaptability and application potential for our method.

Shell egg freshness is the key factor of evaluating egg quality. This review summarizes evaluation methods, influence factors of shell egg freshness, methods of retarding shell egg freshness deteriorations and future research directions of shell egg freshness. The results shows that egg freshness can be possibly evaluated by combination of destructive testing technology and non-destructive testing technology in an objective, dynamic and on-line manner. Hen age, diet, storage, transportation and environmental conditions can make a great influence on shell egg freshness. The characteristics of shell egg freshness can be possibly well maintained by adopting young hen, balanced nutrition diets, low temperature storage and avoiding mechanical damages during transportation and storage. Sterilization, packaging and coating methods can probably retard shell egg freshness deteriorations. Partially/totally adopting green, high efficient and energy-saving non-conventional food sterilization methods, and active, biodegradable and intelligent packaging/coating methods can possibly avoid microbial spoilage and retard egg freshness deteriorations during egg preservation. More researches of non-destructive testing technologies, diet formulations, simulating actual production, storage, transportation and sales, as well as optimization of non-conventional food sterilization-packaging and coating technologies need to be further explored, thus achieving quality improvement and industry promotion of shell eggs.

Objective At present, it is still uncertain whether single screw has the same stability as double screws in the treatment of ulnar coronal process basal fracture (Regan–Morry type III). So, we aimed to compare the pull‐out force and anti‐rotation torque of anterior single/double screw‐cancellous bone fixation (aSSBF, aDSBF) in this fracture, and further study the influencing factors on anatomical and biomechanical stability of smart screw internal fixations. Methods A total of 63 adult volunteers with no history of elbow injury underwent elbow CT scanning with associated three‐dimensional reconstruction that enabled the measurements of bone density and fixed length of the proximal ulna and coronoid. The models of coronal process basal fracture, aSSBF and aDSBF, were developed and validated. Using the finite element model test, the sensitivity analysis of pull‐out force and rotational torque was carried out. Results The pull‐out force of aSSBF model was positively correlated with the density of the cancellous bone and linearly related to the fixed depth of the screw. The load pattern of pull‐out force of aDSBF model was similar to that of aSSBF model. The ultimate torque of aDSBF model was higher than that of aSSBF model, but the load pattern of ultimate torque of both models was similar to each other when the fracture reset was satisfactory, and the screw nut attaches closely to coronoid process. Moreover, with enhancement of initial pre‐tightening force, the increase of ultimate torque of both models was small. Conclusions In addition to three pull‐out stability factors of smart screw fixations, fracture surface fitting degree and nut fitting degree are the other two important anatomical and biomechanical stability factors of smart screw fixations both for rotational stability. When all pull‐out stability and rotational stability factors meet reasonable conditions simultaneously, single or double screw fixation methods are stable for the treatments of ulnar coronoid basal fractures.

[Introduction] The compressed air energy storage power station lacks corresponding codes as technical support in the design of main power House. There are some controversial and inapplicable provisions in the Code for design of compressed air station, which is difficult to meet the needs of the current large-scale development of compressed air storage power station. The paper aims to solve these critical problems in the implementation of the codes and to find better design schemes for the main power House. [Method] The explosion risks of the air energy storage compressor were analyzed, an economic comparison between the combined power House design and the separate power House design was made, and the storage volume of compressed air in the compressor room was sorted out and summarized. [Result] The results show that the air energy storage compressor has no chemical explosion hazard, and no physical explosion hazard on the premise that the equipment′s quality meets the standard. Combined power House design can save a lot of investment compared with separate power House design. The storage volume of compressed air in the compressor room is smaller than that of the main power House. [Conclusion] From the perspective of process flow, system integration, overall economy, convenient operation and maintenance, combined power House design is recommended for the main power House of a large-scale compressed air energy storage power station. According to the process layout and maintenance operation requirements, large platform structure is also recommended. A class-A fire door can be set up when the compressor power House is adjacent to other rooms, and the door buckets together with other protective measures should be set up.

Hydroxylation at the C-14 position of triptolide is critical for its potent antitumor activity. Here, the authors report two CYP82Ds catalyze the 14-hydroxylation reaction via metabolic grid and achieve heterologous bioproduction of triptolide precursor in engineered Saccharomyces cerevisiae.

Plant‐based flow microreactors with natural channel structures, renewable properties, and environmental friendliness have increasingly gained popularity in heterogeneous catalysis. However, firmly immobilizing the catalysts simultaneously with ease and adaptability, maintaining great effectivity and long‐term stability, is still a fundamental challenge. Herein, a highly efficient and ultrastable bamboo‐based catalytic microreactor (CMR) containing mesoporous TiO2 (M‐TiO2)‐encapsulating ultrafine Pd nanoparticles (NPs) is constructed for the continuous‐flow hydrogenation of nitroaromatics. The fabrication of the Pd‐TiO2 catalysts in required bamboo microchannels (Pd‐TiO2/B CMR) mainly involves a two‐step region‐selective synthetic strategy with ultra‐low chemical usage, fast preparation, and low catalyst loading (0.007 wt%). The M‐TiO2 films: 1) provide abundant oxygen vacancies and enough open cavities to facilitate the growth of Pd NPs; 2) improve Pd dispersion and reduce particle size; 3) allow diffusion of reactants, and 4) induce strong metal‐support interactions for enhanced catalytic activity and stability. The optimized Pd‐TiO2/B CMR demonstrates high efficiency (>97%) and excellent stability (1,000 h) for the continuous‐flow hydrogenation of nitroaniline, even under intermittent operation (12 h on/12 h off for five cycles) or in a real aqueous matrix (>200 h), making it a promising candidate for Pd‐catalyzed hydrogenation.

Objective: To develop novel multiparametric models based on computed tomography enterography (CTE) scores to identify endoscopic activity and surgical risk in patients with Crohn's disease (CD). Methods: We analyzed 171 patients from 3 hospitals. Correlations between CTE outcomes and endoscopic scores were assessed using Spearman's rank correlation analysis. Predictive models for moderate to severe CD were developed, and receiver operating characteristic (ROC) curves were constructed to determine the area under the ROC curve (AUC). A combined nomogram based on CTE scores and clinical variables was also developed for predicting moderate to severe CD and surgery. Results: CTE scores were significantly correlated with endoscopy scores at the segment level. The global CTE score was an independent predictor of severe (HR = 1.231, 95% CI: 1.048–1.446, p = 0.012) and moderate-to-severe Simplified Endoscopic Scores for Crohn's Disease (SES-CD) (HR = 1.202, 95% CI: 1.090–1.325, p

Background: Sepsis has become a global health concern owing to its increasing incidence and high mortality rate. In the present study, we investigated a novel drug candidate ASK0912 on its protective effects in mice with Acinetobacter baumannii 20–1-induced sepsis, and studied the related mechanisms. Material and methods: To analyze the protective effect of ASK0912 on septic mice, survival rates, body temperature, organ and blood bacterial loads, white blood cell and platelet counts, organ damage, and cytokine levels were determined. Results: ASK0912 remarkably increased the survival rate of mice with sepsis induced by A. baumannii 20–1 at a low dose of 0.6 mg/kg. Rectal temperature measurements showed that ASK0912 treatment prevented the body temperature decrease of septic mice to some extent. Treatment with ASK0912 can notably reduce the organ and blood bacterial loads and alleviate platelet count reduction due to sepsis. ASK0912 attenuated organ damage, including reduced levels of total bile acids, urea, and creatinine, aggregation of inflammatory cells, and mitigation of structural changes in septic mice, as demonstrated by biochemical analysis and hematoxylin & eosin staining. Additionally, multiplex assay showed that abnormally increased cytokine levels (IL-1β, IL-3, IL-5, IL-6, IL-10, IL-13, MCP-1, RANTES, KC, MIP-1α, MIP-1β, and G-CSF) in septic mice decreased after ASK0912 treatment. Conclusions: ASK0912 can not only improve the survival rate, hypothermia, lower the bacterial loads in the organs and blood, but also alleviate the pathophysiological manifestations such as intravascular coagulation abnormalities, organ damages, and immune system disorder of sepsis mice induced by A. baumannii 20–1.

The risk of algal blooms in landscape water bodies replenished by reclaimed water (RW) prompted the scientific management of RW discharge issues. Mathematical models are concise and convincing methods to stimulate algal growth and calculate thresholds for water quality control. This study presented three types of models, including one-parameter models, multiple-parameter models, and ecosystem dynamic models. Key influencing factors (such as nutrient concentration, light intensity, temperature, biotic processes, specific hydraulic conditions, etc.) are taken into consideration in these models. The work provided feasible methods for the management of reclaimed water to prevent water bloom outbreaks.

In the past few decades, breast cancer has rapidly increased the death rate among women worldwide. An early diagnosis of such fatal disease is important for the best treatment and death rate reduction. Automatic diagnosis of breast cancer from histopathological images using artificial intelligence (AI) based methods is a top-priority research area in the biomedical field. However, automatic detection is challenging due to high resolution of histopathology images and the tremendous amount of parameters required by deep AI models. Due to high computational complexity and bulky memory usage, deep models suffer from inefficient inference that limits their application in resource-constrained platforms. To address this problem, a fast cancer detection strategy has been proposed to overcome the computational cost issue of deep automatic systems. Instead of directly using input images the wavelet transform (WT) is applied to decompose the images into different frequency bands and then only low frequency bands are subjected to our proposed lightweight deep convolutional neural network (CNN). The lightweight deep model is designed using invertible residual block module. The incorporation of invertible residual block module in the deep CNN model and the use of WT considerably reduces the computational cost of the proposed model, without a noticeable accuracy downgrade Further, the effect of various machine vision classifiers i.e. support vector machine (SVM), softmax, and K nearest neighbor classifier (KNN) on model performance is analyzed. Experiments are performed using three publicly available benchmark histopathology image datasets. The proposed model has shown multi-class classification accuracy of 96.25%, and 99.8% and 72.2%, on the international conference on image analysis and recognition (ICIAR 2018), BreakHis and Bracs datasets, respectively. The reported inference time per image of the proposed model is 0.67s, and 0.21s for ICIAR 2018 and BreakHis and Bracs images, respectively.

In this study, a novel family of single-phase, bridgeless, three-level power factor correction (PFC) topologies was proposed based on the embedded construction scheme. These technologies combined bridgeless PFC circuits and multilevel technology. These topologies are highly suitable for applications with high efficiency and high power density requirements. This family has six topologies. The derivation, operating principle, mathematical model, and circuit performance of the proposed topologies were analyzed. Furthermore, for this family of topologies, a four-carrier phase disposition pulse width modulation (FCPD-PWM) method and a system design method were proposed. Finally, an experimental prototype with an output power of 1 kW was designed. The circuit can work in the PFC mode under the rated working conditions and reflects the characteristics of three levels. The circuit can respond quickly and work normally under a variety of complex working conditions and can work in a diode rectification mode when the driving voltage signal is lost. The experimental results demonstrated the feasibility of the topology derived from the proposed embedded construction scheme and the effectiveness of the FCPD-PWM method for driving the proposed three-level conversion circuit.

The Covid-19 pandemic is a prevalent health concern around the world in recent times. Therefore, it is essential to screen the infected patients at the primary stage to prevent secondary infections from person to person. The reverse transcription polymerase chain reaction (RT-PCR) test is commonly performed for Covid-19 diagnosis, while it requires significant effort from health professionals. Automated Covid-19 diagnosis using chest X-ray images is one of the promising directions to screen infected patients quickly and effectively. Automatic diagnostic approaches are used with the assumption that data originating from different sources have the same feature distributions. However, the X-ray images generated in different laboratories using different devices experience style variations e.g., intensity and contrast which contradict the above assumption. The prediction performance of deep models trained on such heterogeneous images of different distributions with different noises is affected. To address this issue, we have designed an automatic end-to-end adaptive normalization-based model called style distribution transfer generative adversarial network (SD-GAN). The designed model is equipped with the generative adversarial network (GAN) and task-specific classifier to transform the style distribution of images between different datasets belonging to different race people and carried out Covid-19 detection effectively. Evaluated results on four different X-ray datasets show the superiority of the proposed model to state-of-the-art methods in terms of the visual quality of style transferred images and the accuracy of Covid-19 infected patient detection. SD-GAN is publicly available at: https://github.com/tasleem-hello/SD-GAN/tree/SD-GAN.

Weeds infestation causes damage to crops and limits the agricultural production. The traditional weeds controlling methods rely on agrochemicals which demand labour-intensive practices. Various methods are proposed for the pursuit of weeds detection using multispectral images. The machine vision-based weeds detection methods require the extraction of a large number of multispectral texture features which in turn increases the computational cost. Deep neural networks are used for pixel-based weeds classification, but a drawback of these deep neural network-based weeds detection methods is that they require a large size of images dataset for network training which is time-consuming and expensive to collect particularly for multispectral images. These methods also require a Graphics Processing Unit (GPU) based system because of having high computational cost. In this article, we propose a novel weeds detection model which addresses these issues, as it does not require any kind of supervised training using labelled images and multispectral texture features extraction. The proposed model can execute on a Central Processing Unit (CPU) based system as a result its computational cost reduces. The Predictive Coding/Biased Competition-Divisive Input Modulation (PC/BC-DIM) neural network is used to determine multispectral fused saliency map which is further used to predict salient crops and detect weeds. The proposed model has achieved $\textbf {94.38} \%$ mean accuracy, $\textbf {0.086}$ mean square error, and $\textbf {0.291}$ root mean square error.

Abstract Background Almost all traditional Chinese medicine (TCM) quality of life measures are non-preference-based measures (non-PBMs), which do not provide utilities for cost-utility analysis in pharmacoeconomic evaluation. Whereas the mapping has become a new instrument to obtain utilities, which builds a bridge between non-PBMs and PBMs. Purpose To develop mapping algorithms from the health status scale of traditional Chinese medicine (TCM-HSS) onto the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L). Methods The cross-sectional data were collected by questionnaire survey from a tertiary hospital visit population and community residents in China, and randomly divided into training and validation set by 2:1. Based on the training set, direct and indirect mapping methods (7 regression methods and 4 model specifications) were conducted to establish alternative models, which were comprehensively evaluated based on the validation set by mean absolute error, root mean square error, and Spearman correlation coefficient between predicted and observed values. Based on the whole sample, the preferred mapping algorithm was developed. Results A total of 639 samples were included, with an average age of 45.24 years and 61.66% of respondents were female. The mean EQ-5D-3L index was 0.9225 [SD = 0.1458], and the mean TCM-HSS index was 3.4144 [SD = 3.1154]. The final mapping algorithm was a two-part regression model including the TCM-HSS subscales, interaction terms, and demographic covariates (age and gender). The prediction performance was good. The mean error was 0.0003, the mean absolute error was 0.0566, the root mean square error was 0.1039, and 83.10% of the prediction errors were within 0.1; the Spearman correlation coefficient between predicted and observed EQ-5D-3L values was 0.6479. Conclusion It is the first study to develop a mapping algorithm between the TCM-HSS and EQ-5D-3L, which demonstrates excellent prediction accuracy and estimates utility value for economic evaluation from TCM quality of life measures.

Abstract Background Hepatocellular carcinoma (HCC) belongs to a representative lethality gastrointestinal malignancy, and comprehensive management of HCC remains intractable at present on account of its invasive biological feature that is easy to relapse and early metastasis. The intimate connection between platelets and tumor progression has been widely reported, and platelet-related indicators are also used in the clinical practice of carcinoma. This work is designed to investigate the significance of platelet-related genes in the prognostic prediction of patients with HCC and their potential role in the cross-talk between HCC cells and platelets in the tumor microenvironment. Methods By integrating the RNA-seq data and clinicopathological information of HCC patients, we extracted prognosis-associated platelet-related genes based on the univariate cox analysis and further established a relevant prognostic signature via the lasso cox regression analysis, and two independent HCC cohorts were used as external validation. Multiple bioinformatics methods were utilized to explore the underlying functional discrepancy between different risk groups classified by the risk model. And in vitro proliferation, invasion, and migration assays were conducted to investigate the effect of platelet stimulation on HCC cells’ viability and motility, and flow cytometric analysis was exerted to demonstrate the influence of HCC cells on platelet activation. Results A novel platelet-related risk model was developed and patients both in the training and testing cohorts were divided into distinct risk subgroups according to the median risk score. It was observed that the high-risk status was closely associated with poor prognosis and worse clinicopathological parameters. Meanwhile, an obvious discrepancy in the constitution of the immune microenvironment also indicated that distinct immune status might be a potential determinant affecting prognosis as well as immunotherapy reactiveness. Moreover, in vitro experiments demonstrated that PRKCD could act as a molecular bridge between tumor cells and platelets, which could either participate in regulating tumor malignant phenotype or mediating platelet activation. Conclusions In brief, this work reveals a novel platelet-related risk signature for prognostic evaluation of HCC patients and confirms that PRKCD is a key messenger in HCC cell-platelet interaction and plays a crucial role in mediating platelet-induced tumor progression.