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Background: The association between dipeptidyl peptidase-4 inhibitors (DPP-4i) exposure and the risk of colorectal cancer (CRC) in patients with type 2 diabetes mellitus (T2DM) is unclear. Objectives: This meta-analysis aims to investigate the relationship between DPP-4i exposure and the incidence of CRC in patients with T2DM. Design: A systematic review and meta-analysis. Methods: A comprehensive search of electronic databases, including PubMed, Web of Science, EMBASE, and ScienceDirect, was conducted up to March 2024. The studies including randomized clinical trials (RCTs), cohort studies, and case–control studies were retrieved. The odds ratio (OR) was calculated using Stata 12.0 statistical software. The primary outcome assessed was the incidence of CRC. Results: This meta-analysis incorporated six retrospective cohort studies and two case–control studies. The findings indicate that the incidence of CRC in the DPP-4i exposure group was significantly higher than that in the control group (OR = 1.11, 95% CI: 1.02–1.21, p = 0.013). Subgroup analysis revealed that both male (OR = 2.07, p

BackgroundAntibody-drug conjugate (ADC) is an anticancer drug that links toxins to specifically targeted antibodies via linkers, offering the advantages of high target specificity and high cytotoxicity. However, complexity of its structural composition poses a greater difficulty for drug design studies.ObjectivesPharmacokinetic/pharmacodynamic (PK/PD) based consideration of ADCs has increasingly become a hot research topic for optimal drug design in recent years, providing possible ideas for obtaining ADCs with desirable properties.MethodsFrom the assessment of the ADC action process based on PK/PD, we introduce the main research strategies of ADCs. In addition, we investigated the strategies to solve the prominent problems of ADC in the clinic in recent years, and summarized and evaluated the specific ways to optimize various problems of ADC based on the PK/PD model from two perspectives of optimizing the structure and properties of the drugs themselves. Through the selection of target antigen, the optimization of the linker, the optimization of novel small molecule toxins as payload, the optimization of ADC, overcoming the multi-drug resistance of ADC, improving the ADC tumor penetration of ADC, surface modification of ADC and surface bystander effect of ADC provide a more comprehensive and accurate framework for designing new ADCs.ResultsWe’ve expounded comprehensively on applying pharmacokinetics or pharmacodynamics while designing ADC to obtain higher efficacy and fewer side effects. From the ADC’s PK/PD property while coming into play in vivo and the PK/PD study strategy, to specific ADC optimization methods and recommendations based on PK/PD, it has been study-approved that the PK/PD properties exert a subtle role in the development of ADC, whether in preclinical trials or clinical promotion.ConclusionThe study of PK/PD unfolds the detailed mechanism of ADC action, making it easier to control related parameters in the process of designing ADC, limited efficacy and inevitable off-target toxicity remain a challenging bottleneck.

Abstract Background Preference-based measures of health-related quality of life (HRQoL), such as the EQ-5D or the SF-6D, are essential for health economic evaluation. However, they are rarely included in clinical trials of ankylosing spondylitis (AS). This study aims to develop mapping algorithms to predict EQ-5D-3L and EQ-5D-5L health utility scores from the Bath Ankylosing Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). Methods Patients with AS were recruited from the largest tertiary hospital in Shandong province, China, between December 2019 and October 2020. Patients were selected by convenience sampling method according to the following criteria: (1) diagnosed with AS according to the New York criteria; (2) aged 18 years and above; and (3) without mental disorders; (4) able to understand the questionnaires; (5) without serious complications. There were 243 patients who completed the face-to-face questionnaire survey, and 5 cases with missing values in key variables were excluded. Ordinary least squares, censored least absolute deviations, Tobit, adjusted limited dependent variable mixture model and beta-mixture model (BM) in the direct approach and ordered logit and multinomial logit (Mlogit) model in the response approach were used to develop mapping algorithms. Mean absolute error, root mean square error, Spearman’s correlation coefficient and concordance correlation coefficient were used to access predictive performance. Results The 238 patients with AS had a mean age of 35.19 (SD = 9.59) years, and the majority (74.47%) were male. The observed EQ-5D-3L and EQ-5D-5L health utility values were 0.88 (SD = 0.12) and 0.74 (SD = 0.27), respectively. The EQ-5D-5L had higher conceptual overlap with the BASDAI and BASFI than the EQ-5D-3L did. The Mlogit was the best-performing model for the EQ-5D-3L, and the BM showed better performance in predicting EQ-5D-5L than other direct and indirect mapping models did. Conclusion This study demonstrates that the EQ-5D-5L, rather than EQ-5D-3L, should be selected as the target outcome measure of HRQoL in patients with AS in China, and the BM mapping algorithm could be used to predict EQ-5D-5L values from BASDAI and BASFI for health economic evaluation.

Background: Triple negative breast cancer (TNBC) is a deadly subtype of breast cancer with limited treatment options. Currently, programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have become the first choice for breast cancer immunotherapies. Despite paclitaxel being considered a cornerstone drug in breast cancer treatment, the effectiveness, safety, and optimal drug selection for its combination with PD-1/PD-L1 inhibitors remain uncertain. Methods: We conducted a systematic review and network meta-analysis, performing a comprehensive literature search across PubMed, Embase, and the Cochrane Library from the inception of each database through May 18, 2024. Selected trials were those that assessed the efficacy and safety of paclitaxel-based PD-1/PD-L1 therapies for the treatment of TNBC. The primary endpoint assessed was overall survival (OS), while secondary outcomes included progression-free survival (PFS), adverse events (AEs), overall response rate (ORR), and Pathological complete response (pCR). This study is registered in PROSPERO under registration number CRD42023429651. Results: A total of 8 RCTs meeting our eligibility criteria were included, involving 4626 patients who received either Paclitaxel (Paclitaxel-placebo/chemotherapy) or a combination of durvalumab, pembrolizumab, atezolizumab, toripalimab with paclitaxel. The pooled results demonstrated that Durvalumab combined with Paclitaxel significantly reduced the hazard ratio for OS (surface under the cumulative ranking [SUCRA]: 91.05%) and PFS compared with Paclitaxel alone (SUCRA: 83.52%). Additionally, Durvalumab plus Paclitaxel significantly improved the ORR compared with Paclitaxel (odds ratio [OR]: 2.30; 95% credible interval [CrI]: 1.10–5.20). For safety outcomes, Atezolizumab plus Paclitaxel showed a favorable profile in AEs, with no significant differences observed between groups. In the pCR study, Pembrolizumab plus Paclitaxel was the most effective treatment option (SUCRA: 81.85%). Conclusions: When combined with paclitaxel, PD-1/PD-L1 inhibitors exhibit a favorable survival benefit. The combination of Durvalumab and paclitaxel represents the optimal treatment option. In the future, attention should be paid to the TNBC subtypes and drug dosage, as these factors may help to design personalized TNBC treatment programs.

BackgroundNeoadjuvant immunotherapy holds promise in managing resectable locally advanced gastric cancer (GC), adenocarcinoma of the esophagogastric junction (AEG), and esophageal cancer (EC). However, consensus is lacking regarding the efficacy of programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors in neoadjuvant immunochemotherapy (NICT). This study aims to assess the added benefit of PD-1/PD-L1 inhibitors in neoadjuvant chemotherapy (NCT) for these malignancies.MethodsUp to October 2024, randomized controlled trials, case-control studies, and cohort studies that evaluated the addition of PD-1/PD-L1 inhibitors to NCT were systematically retrieved from electronic databases. The primary endpoints included pathologic complete response (pCR), major pathological response (MPR), overall survival (OS), and progression-free survival (PFS).ResultsThirteen studies published between 2021 and 2024 were analyzed. Statistical analyses revealed significantly higher pCR rates (OR: 2.73, P < 0.001) and MPR rates (OR: 2.99, P < 0.001) in the NICT group compared to NCT group. The PFS was also higher in the NICT group, although the difference did not reach statistical significance (HR: 0.50, P = 0.072).ConclusionThis meta-analysis demonstrates that NICT enhances pathological response rates in patients with resectable locally advanced GC, AEG, and EC. However, no significant long-term prognostic benefits were associated with NICT.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42024545725.

The regulation of infrared (IR) thermal radiation has received widespread attention; the proposals have been made for various devices that use electrochromic materials. However, the visible appearance of the mentioned devices also changes when the IR states are altered. Herein, the memristive mechanism is utilized to regulate IR emissivity and design a novel transparent memristor‐type modulator featuring an Indium tin oxide (ITO)/HfO2/ITO structure. The modulator exhibits a dynamic emissivity variation of 0.38 in the IR region of 2.5–25 μm, without compromising transparency in the visible region under the application of an electric voltage. The migration of oxygen vacancies results in the modification of interface barriers and the formation of oxygen vacancy‐enriched regions, thereby enabling the modulator to exhibit resistive switching behavior and regulate IR emissivity. An array of modulators is also assembled, demonstrating the ability to independently display visible and IR information. In this work, new possibilities are presented for various applications such as multispectral displays, energy‐efficient thermoregulation, encrypted information displays, and camouflage.

BackgroundPrevious studies have suggested a correlation between dietary inflammatory potential and non-alcoholic fatty liver disease (NAFLD). Therefore, the study aimed to investigate the association between dietary inflammatory potential, measured by the dietary inflammation index (DII), and NAFLD.MethodsFrom establishing the database to June 2023, a systematic search of PubMed, Web of Science, Embase and Cochrane Library were performed to identify relevant observational studies. These studies reported a correlation between DII and NAFLD. The meta-analysis used odds ratio (OR) with 95% confidence intervals (CI) to evaluate the relationship between DII and NAFLD.ResultsEight studies were included in this meta-analysis after excluding irrelevant records. A summary of the results from the included studies showed that the risk of NAFLD was higher in those exposed to higher DII (OR = 1.26, 95%CI 1.12 to 1.40, p

This study investigated the impacts of light spectra on oxidative stress and nutrient quality of the fish Plectropomus leopardus in indoor recirculating aquaculture systems. The fish (100 g ± 0.45 g [wet weight]) were cultures in five different light spectra (full-spectrum (400–800 nm), blue (450 nm), green (530 nm), red (630 nm), and dark) for 60 days. After experimentation, blood and muscle tissue were collected and analyzed for biochemical variables and nutritional quality. We demonstrated that the total cholesterol, triglycerides activities of P. leopardus in the dark groups were substantially elevated, relative to other groups (p < 0.05). Glutathione and glutathione peroxidase activities were elevated in the green light group versus other red groups, and cortisol was drastically reduced in the red group relative to other groups (p < 0.05). The crude ash concentration in the blue and full-spectrum group was substantially more elevated than in other groups (p < 0.05). Thr, Glu, Cys, Val, Met, Ile, Leu, Phe, Lys, His, Arg were markedly higher in the blue light versus the red light group (p < 0.05). The muscle of P. leopardus was rich in lysine and its essential AA index was in the order of blue light, full-spectrum, green light, dark and red group. The content of total saturated fatty acids in the blue light group was drastically lower relative to the dark, green and red groups (p < 0.05), and the total polyunsaturated fatty acids and DHA + EPA contents in the blue light group were substantially elevated relative to the other groups (p < 0.05). These results revealed that different light environments had certain effects on blood biochemical, antioxidant capacity, nutrient composition and proportion of P. leopardus. A comprehensive evaluation found that the blue light environment had more positive effects on the physiological, biochemical and nutritional quality of P. leopardus. This result provides a theoretical reference for the lighting strategy of an indoor recirculating aquaculture system.

Photoperiod serves as a significant environmental signal for organisms and plays a critical role in regulating their metabolic processes. This research aimed to investigate the lipid metabolism and nutritional quality of adults Litopenaeus vannamei (wet weight: 11.27 ± 0.73 g, body length: 12.45 ± 0.42 cm) under five photoperiods (0L:24D, 8L:16D, 12L:12D, 16L:8D, and 24L:0D) for 40 days in recirculating water systems (RASs). The 24L:0D group increased lipid metabolism, as indicated by increased lipid metabolism enzyme levels and related gene expression linked to lipogenesis. Additionally, shrimp in the 24L:0D exhibited the highest value of crude fat. The 0L:24D showed a significantly reduced content of crude fat compared with the 8L:16D and 12L:12D. In 24L:0D, the content of total essential amino acids (TEAAs), total hydrolyzed essential amino acids (THEAAs), and total non-essential amino acids (TNEAAs) increased significantly. Similarly, the content of polyunsaturated fatty acids (PUFAs) in 24L:0D was also higher than in other groups. Conversely, 0L:24D resulted in lower metabolic activity and a reduction in PUFA content. In conclusion, prolonging light could benefit shrimp cultivation. This study thoroughly examined the effects of varying photoperiods on muscle quality and lipid metabolism in L. vannamei, providing essential insights for the improvement of indoor aquaculture environments. Provision of light for 24 h improves production but has some adverse effects on animal welfare, so a 16 h light cycle is recommended.

Objective We aimed to provide a comprehensive assessment of health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) of different activities and to evaluate the correlation between clinical activity measures and HRQoL instruments. This research also analysed the extent to which different aspects of HRQoL (physical, psychological and social) were affected.Design Cross-sectional, observational, non-interventional study.Setting The study was conducted at the Department of Rheumatology and Immunology, Qilu Hospital, Shandong University.Methods From December 2019 to October 2020, a total of 340 RA patients participated in the survey using convenient sampling. Three generic instruments, EQ-5D-5L,SF-12 and the AQoL-4D, as well as an RA-specific instrument,the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI), were administered to assess patients’ HRQoL. The Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) was used by doctors to measure patients’ clinical activity. Multivariable linear regression was used to compare patients’ HRQoL across different levels of activity. Spearman’s correlation was used to assess the correlation between doctor-reported clinical activity and HRQoL.Results A total of 314 patients with RA participated in this study. The mean score of HAQ-DI was 0.87 (SD: 0.91). Using patients in the clinical remission group as a reference, patients in the moderate and high disease activity groups showed significantly reduced health state utility values and HRQoL scores (all p

Loss of cerebral cholinergic neurons and decreased levels of acetylcholine (ACh) are considered to be major factors causing cognitive dysfunction in Alzheimer’s disease (AD). Abnormally elevated levels of acetylcholinesterase (AChE) resulting in decreased levels of ACh are common in AD patients; thus, AChE inhibitors (AChEIs) are widely used for the treatment of AD. In our previous work, we acquired DNA aptamers Ob1, Ob2, and Ob3 against human brain AChE from systematic evolution of ligands by exponential enrichment (SELEX). In this study, we investigated the effect of these aptamers on learning and memory abilities, as well as the underlying mechanism in a 5×FAD transgenic AD mouse model. Here, we showed that only aptamer Ob2 exhibits a good inhibitory effect on both mouse and human AChE activity. In addition, chronic treatment with aptamer Ob2 significantly improved cognitive ability of 5×FAD mice in the Morris water maze. Moreover, the mechanism of aptamer Ob2 in 5×FAD mice may be associated with its inhibition of AChE activity, alleviation of the levels of Aβ by lowering the expression of β-secretase (BACE1), and activation of astrocytes in the brains of 5×FAD mice. These results indicate that aptamer Ob2 exhibits potential as an effective AChEI for the treatment of AD.

Abstract Background While ondansetron (OND) is widespread availability, the contribution of OND to improve patient outcomes among intensive care unit (ICU) patients has not been examined. This study aimed to illustrate the association between early OND use and in-hospital mortality in critically ill patients and investigate whether this association differed according to OND dose. Methods The MIMIC-IV database was employed to identify patients who had and had not received OND. Statistical approaches included multivariate logistic regression, propensity score matching (PSM), and propensity score-based inverse probability of treatment weighting (IPTW) models to ensure the robustness of our findings. Results In total, 51,342 ICU patients were included. A significant benefit in terms of in-hospital mortality was observed in the OND patients compared to the non-OND group in the early stage [odds ratio (OR) = 0.75, 95% CI 0.63–0.89, p

Abstract The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.

Light has long been known to have a profound influence on the growth and development of fish. The previous studies showed that different spectra had different effects on the growth of juvenile Takifugu rubripes. Among them, green light can promote the growth of Takifugu rubripes, but the influence mechanism is unknown. In this study, how different LED spectrums affect fish growth from the perspective of GH/IGF-I axis-related genes and apoptosis genes were deeply explored. In the experiment, juvenile Takifugu rubripes with an initial body length of (9.01 ± 0.70) cm and an initial body weight of (18.05 ± 3.17) g were selected as the research objects. 525 Takifugu rubripes juveniles were selected, cultured and monitored in five different LED spectrum treatment groups: white light (WL, λ 400-780nm), red light (RL, λ 625-630nm), yellow light (YL, λ 590-595nm), green light (GL, λ 525-530nm) and blue light (BL, λ 450-455nm). The photoperiod was 12L:12D, and the light intensity was set to 250 mW/m2. The effects of light spectrum on growth, melatonin synthesis, GH/IGF-I axis and relative expressions of apoptosis-related genes in juvenile Takifugu rubripes were studied, including arylalkylamine N-acetyltransferase (AANAT2), growth hormone (GH), growth hormone receptor type 1 (GHR1), growth hormone releasing hormone (GHRH), insulin-like growth factor type I (IGF-I), insulin-like growth factor type II (IGF-II), insulin-like growth factor binding protein (IGFBP), Bcl-2 protein family (Bcl-2), tumor suppressor (p53) and cysteine protease family (caspase 3, caspase 8, caspase 10) genes. The results showed that the final weight was the highest in the GL group (29.36 ± 3.78 g) and the lowest in the YL group (21.28 ± 2.56 g). The GL indeed promote the growth of Takifugu rubripes. The GHR1, IGF-I, IGF-II and IGFBP of juvenile Takifugu rubripes cultured under GL were significantly higher than those of WL (control group), BL and YL groups. The relative expression levels of GH and GHRH genes had no difference from those in the WL control group, and the relative expression levels of apoptosis genes in the GL group were significantly lower than those in the BL and YL groups. Under RL, the relative expression levels of all growth genes on the GH/IGF-I growth axis were relatively high. But at the same time, the relative expression of caspase 10 gene in juvenile Takifugu rubripes was high, and the growth state was inhibited. It is speculated that RL might disturb the endocrine system of the juvenile Takifugu rubripes, thus impeded its growth and development. Therefore, different LED spectra can affect the growth of juvenile Takifugu rubripes by affecting the expressions of GH/IGF-I growth axis and apoptosis-related genes: GL significantly promotes the growth of Takifugu rubripes, which may be due to that GL promoted the expressions of growth factors genes such as GHR1, IGF-I, and IGF-II, and decreased the expression of apoptosis-related genes, while the situation in the YL, BL and WL groups was on the contrary. RL significantly inhibited the growth of juvenile Takifugu Rubripes, which may be due to the fact that juvenile Takifugu Rubripes under RL were in a stressful state and the high expression of growth axis-related genes was not sufficient to offset the negative effects of the stress response, resulting in the inhibition of growth performance.

Exposure to ammonia can cause convulsions, coma, and death. In this study, we investigate the effects of ammonia exposure on immunoregulatory and neuroendocrine changes in Takifugu rubripes. Fish were sampled at 0, 12, 24, 48, and 96 h following exposure to different ammonia concentrations (0, 5, 50, 100, and 150 mg/L). Our results showed that exposure to ammonia significantly reduced the concentrations of C3, C4, IgM, and LZM whereas the heat shock protein 70 and 90 levels significantly increased. In addition, the transcription levels of Mn-SOD, CAT, GRx, and GR in the liver were significantly upregulated following exposure to low ammonia concertation, however, downregulated with increased exposure time. These findings suggest that ammonia poisoning causes oxidative damage and suppresses plasma immunity. Ammonia exposure also resulted in the elevation and depletion of the T3 and T4 levels, respectively. Furthermore, ammonia stress induced an increase in the corticotrophin-releasing hormone, adrenocorticotropic hormone, and cortisol levels, and a decrease in dopamine, noradrenaline, and 5-hydroxytryptamine levels in the brain, illustrating that ammonia poisoning can disrupt the endocrine and neurotransmitter systems. Our results provide insights into the mechanisms underlying the neurotoxic effects of ammonia exposure, which helps to assess the ecological and environmental health risks of this contaminant in marine fish.

Abstract Background COVID-19 pandemic has forced physicians to quickly determine the patient’s condition and choose treatment strategies. This study aimed to build and validate a simple tool that can quickly predict the deterioration and survival of COVID-19 patients. Methods A total of 351 COVID-19 patients admitted to the Third People’s Hospital of Yichang between 9 January to 25 March 2020 were retrospectively analyzed. Patients were randomly grouped into training (n = 246) or a validation (n = 105) dataset. Risk factors associated with deterioration were identified using univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression. The factors were then incorporated into the nomogram. Kaplan-Meier analysis was used to compare the survival of patients between the low- and high-risk groups divided by the cut-off point. Results The least absolute shrinkage and selection operator (LASSO) regression was used to construct the nomogram via four parameters (white blood cells, C-reactive protein, lymphocyte≥0.8 × 109/L, and lactate dehydrogenase ≥400 U/L). The nomogram showed good discriminative performance with the area under the receiver operating characteristic (AUROC) of 0.945 (95% confidence interval: 0.91–0.98), and good calibration (P = 0.539). Besides, the nomogram showed good discrimination performance and good calibration in the validation and total cohorts (AUROC = 0.979 and AUROC = 0.954, respectively). Decision curve analysis demonstrated that the model had clinical application value. Kaplan-Meier analysis illustrated that low-risk patients had a significantly higher 8-week survival rate than those in the high-risk group (100% vs 71.41% and P

ObjectiveAlthough dual anti-HER2 therapy, namely, pertuzumab plus trastuzumab, has shown promising results in patients with HER2-positive breast cancer (BC), it is still unclear whether dual therapy will increase adverse effects (AEs) while ensuring the efficacy compared with trastuzumab monotherapy. We conducted a systematic review and meta-analysis to compare the efficacy and safety of combined therapy with monotherapy.MethodsA systematic search was performed to identify eligible randomized controlled trials (RCTs) that evaluated the administration of dual anti-HER2 therapy [pertuzumab plus trastuzumab or trastuzumab emtansine (T-DM1)] versus monotherapy (trastuzumab or T-DM1). The primary endpoints were overall survival (OS) and progression-free survival (PFS).ResultsFourteen RCTs (8,378 patients) were identified. Compared to monotherapy, dual therapy significantly improved the OS (HR = 0.77, 95% CI: 0.59–0.99) and PFS (HR = 0.74, 95% CI: 0.63–0.86) in advanced BC. In neoadjuvant therapy, dual blockade has a higher ORR rate than monotherapy. Grade 3 or higher febrile neutropenia, diarrhea, and anemia as well as heart failure were more frequently reported in dual therapy compared to monotherapy. No significant difference in serious AEs was observed between the two groups. In the subgroup analysis, compared to single-target therapy, dual-target therapy has higher OS and PFS rates in Asian patients with advanced therapy; however, total grade ≥3 AEs and serious AEs were significantly higher in the dual group in Asian patients.ConclusionsOur study confirms that the combination of pertuzumab and trastuzumab therapy could substantially improve the outcome of patients with HER2-positive breast cancer and was well tolerated compared to trastuzumab monotherapy.

Air pollution is one of the major risk factors for lung disease. Microplastics are a ubiquitous environmental pollutant, both indoors and in outdoor air. Microplastics have also been found in human lung tissue and sputum. However, there is a paucity of information on the effects and mechanisms of microplastics on lung disease. In this mini-review, we reviewed the possible mechanisms by which air microplastics’ exposure affects lung disease and, at the same time, pointed out the limitations of current studies.

Focusing on the components of both solar photovoltaic technology and wind energy technology and using the gravity model approach with panel data, this study empirically investigated the determinants of bilateral trade in renewable energy goods among ASEAN countries as well as with China, Japan, and South Korea for the period 2012–2019, and also identified China’s export efficiency and export potential. The results showed that the economic sizes of both the exporting and importing countries, the economic freedom of the exporter, and trade agreements and membership of common trade areas significantly encouraged bilateral trade, while geographical distance exerted a significantly negative influence. In general, it was found that China had great potential to export renewable energy goods. We propose that the ASEAN Plus Three region needs to formulate and implement a comprehensive and carefully coordinated renewable energy policy package. We also suggest that China should promote joint efforts with ASEAN, Japan and South Korea to further deepen cooperation on the low-carbon economy and tap the great potential for trade in renewable energy goods.

Viral subunit vaccines often suffer low efficacy. We recently showed that when taken out of the context of whole virus particles, recombinant subunit vaccines contain artificially exposed surface regions that are non-neutralizing and reduce their efficacy, and thus these regions need to be re-buried in vaccine design. Here we used the envelope protein domain III (EDIII) of Japanese encephalitis virus (JEV), a subunit vaccine candidate, to further validate this important concept for subunit vaccine designs. We constructed monomeric EDIII, dimeric EDIII via a linear space, dimeric EDIII via an Fc tag, and trimeric EDIII via a foldon tag. Compared to monomeric EDIII or linearly linked dimeric EDIII, tightly packed EDIII oligomers via the Fc or foldon tag induce higher neutralizing antibody titers in mice and also protect mice more effectively from lethal JEV challenge. Structural analyses demonstrate that part of the artificially exposed surface areas on recombinant EDIII becomes re-buried in Fc or foldon-mediated oligomers. This study further establishes the artificially exposed surfaces as an intrinsic limitation of subunit vaccines, and suggests that re-burying these surfaces through tightly packed oligomerization is a convenient and effective approach to overcome this limitation.

BackgroundPosaconazole is confirmed to be more effective for preventing invasive fungal infections (IFIs) than first-generation triazoles (fluconazole and itraconazole), but its economic value has not been comprehensively evaluated in China. This study compared the cost-effectiveness of these two antifungal prophylaxis regimens in hematological-malignancy patients at high risk for IFIs from the Chinese healthcare perspective.MethodsA hybrid decision tree and Markov model were built using published data to estimate the total costs and quality-adjusted life-years (QALYs) of antifungal prophylaxis with posaconazole oral suspension and first-generation triazoles. Regimens with an incremental cost-effectiveness ratio (ICER) lower than the threshold of willingness to pay (WTP) were considered cost-effective. One-way and probabilistic sensitivity analyses were performed to assess model robustness. The regional imbalance of economic development and the tablet formulation of posaconazole were considered in the scenario analyses.ResultsIn the base-case analysis, posaconazole oral suspension provided an additional 0.109 QALYs at an incremental cost of $954.7, yielding an ICER of $8,784.4/QALY, below the national WTP threshold of $31,315/QALY. One-way and probabilistic sensitivity analyses showed that the results were robust. Scenario analyses showed that the base-case ICER was consistently below the WTP thresholds of all 31 Chinese provinces, with the likelihood of posaconazole being cost-effectiveness ranging from 78.1 to 99.0%. When the posaconazole oral suspension was replaced by the tablet formulation, the ICER increased to $29,214.1/QALY, still below the national WTP threshold and WTP thresholds of 12 provinces.ConclusionsPosaconazole oral suspension is a highly cost-effective regimen for preventing IFI in high-risk hematological-malignancy patients from the Chinese healthcare perspective. Posaconazole tablets may also be considered in some high-income regions of China.

With the epidemic of betacoronavirus increasing frequently, it poses a great threat to human public health. Therefore, the research on the pathogenic mechanism of betacoronavirus is becoming greatly important. Murine hepatitis virus strain-3 (MHV-3) is a strain of betacoronavirus which cause tissue damage especially fulminant hepatic failure (FHF) in mice, and is commonly used to establish models of acute liver injury. Recently, MHV-3-infected mice have also been introduced to a mouse model of COVID-19 that does not require a Biosafety Level 3 (BSL-3) facility. FHF induced by MHV-3 is a type of severe liver damage imbalanced by regenerative hepatocellular activity, which is related to numerous factors. The complement system plays an important role in host defense and inflammation and is involved in first-line immunity and/or pathogenesis of severe organ disorders. In this study, we investigated the role of aberrant complement activation in MHV-3 infection-induced FHF by strategies that use C3-deficient mice and intervene in the complement system. Our results showed that mice deficient in C3 had more severe liver damage, a higher viral load in the liver and higher serum concentrations of inflammatory cytokines than wild-type controls. Treatment of C57BL/6 mice with C3aR antagonist or anti-C5aR antibody reduced liver damage, viral load, and serum IFN-γ concentration compared with the control group. These findings indicated that complement system acts as a double-edged sword during acute MHV-3 infection. However, its dysregulated activation leads to sustained inflammatory responses and induces extensive liver damage. Collectively, by investigating the role of complement activation in MHV-3 infection, we can further understand the pathogenic mechanism of betacoronavirus, and appropriate regulation of immune responses by fine-tuning complement activation may be an intervention for the treatment of diseases induced by betacoronavirus infection.

With the development of the social economy, human demand for forest ecosystem service functions is increasing, and at the same time, higher requirements are being put forward for forest ecosystems. Therefore, a more comprehensive and scientific evaluation of forest ecosystem service functions is needed. In order to understand the current status and trends of research on forest ecosystem service functions and value assessment, this study used bibliometric methods and CiteSpace visual analysis to organize and summarize the relevant research. The results show that current research focuses on three aspects: the formulation of forest ecosystem service assessment issues, the classification of ecosystem service functions, and ecosystem service assessment methods. The focus of future research on forest ecosystem services can be summarized as follows: refining the indicators and methods for assessment, extending the research area and scope, analyzing the spatial and temporal dynamics, conducting research on mechanisms of forest ecosystem service functions, and transforming the evaluation results. This study provides an initial insight into the study of forest ecosystem services and a reference for future scholarly research.

Objective This retrospective multicentre observational study was performed to assess the predictors of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF) in emergency departments in China. Methods In total, 1743 consecutive patients with ADHF were recruited from August 2017 to January 2018. Clinical characteristics and outcomes were compared between patients with and without AKI. Predictors of AKI occurrence and underdiagnosis were assessed in multivariate regression analyses. Results Of the 1743 patients, 593 (34.0%) had AKI. AKI was partly associated with short-term all-cause mortality and cost. Cardiovascular comorbidities such as coronary heart disease, diabetes mellitus, and hypertension remained significant predictors of AKI in the univariate analysis. AKI was significantly more likely to occur in patients with a lower arterial pH, lower albumin concentration, higher creatinine concentration, and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Patients treated with inotropic agents were significantly more likely to develop AKI during their hospital stay. Conclusion This study suggests that cardiovascular comorbidities, arterial pH, the albumin concentration, the creatinine concentration, the NT-proBNP concentration, and use of inotropic agents are predictors of AKI in patients with ADHF.

Background. LRRK2 S1647T has been identified as a polymorphic risk variant for Parkinson’s disease (PD) in Chinese individuals. As LRRK2 is the most common genetic cause for PD, it has drawn great interest regarding whether cognitive impairments in PD are related with LRRK2. Purpose. This study aimed to explore the effects of LRRK2 S1647T polymorphism on cognitive function in PD. Method. 90 PD patients were randomly recruited. They underwent a series of clinical evaluations and genetic testing for the LRRK2 S1647T polymorphism. Global intellect and five cognitive domains (language fluency, visuospatial function, attention, memory, and executive function) were compared between S1647T carriers and noncarriers. Results. No differences in motor features were found between two groups, but the executive function evaluation showed that Stroop word colour test time (SWCT-TIME) scores were lower in LRRK2 S1647T carriers than in noncarriers (P=0.017). However, multiple linear regression analysis indicated that the correlation between S1647T polymorphism and SWCT-TIME scores did not reach significant level (P=0.051). Conclusion. Our findings suggest that cognitive impairments are not correlated with different LRRK2 S1647T polymorphisms in Chinese PD individuals.