A Dual-Mechanism Targeted Bioorthogonal Prodrug Therapy.

Bioorthogonal prodrug therapies offer an intriguing two-component system that features enhanced circulating stability and controlled activation on demand. Current strategies often deliver either the prodrug or its complementary activator to the tumor with a monomechanism targeted mechanism, which cannot achieve the desired antitumor efficacy and safety profile. The orchestration of two distinct and orthogonal mechanisms should overcome the hierarchical heterogeneity of solid tumors to improve the delivery efficiency of both components simultaneously for bio-orthogonal prodrug therapies. We herein developed a dual-mechanism targeted bioorthogonal prodrug therapy by integrating two orthogonal, receptor-independent tumor-targeting strategies. We first employed the endogenous albumin transport system to generate the in situ albumin-bound, bioorthogonal-caged doxorubicin prodrug with extended plasma circulation and selective accumulation at the tumor site. We then employed enzyme-instructed self-assembly (EISA) to specifically enrich the bioorthogonal activators within tumor cells. As each targeted delivery mode induced an intrinsic pharmacokinetic profile, further optimization of the administration sequence according to their pharmacokinetics allowed the spatiotemporally controlled prodrug activation on-target and on-demand. Taken together, by orchestrating two discrete and receptor-independent targeting strategies, we developed an all-small-molecule based bioorthogonal prodrug system for dual-mechanism targeted anticancer therapies to maximize therapeutic efficacy and minimize adverse drug reactions for chemotherapeutic agents.

The efficacy and safety of prophylactic antibiotics for post-acute stroke infection: A systematic review and meta-analysis.

AIMS: Infections are common complications after stroke and associated with unfavourable outcomes. We aimed to evaluate the efficacy and safety of prophylactic antibiotics for post-acute stroke infection. METHODS: We searched PubMed, Embase, the Cochrane Library, SinoMed, China National Knowledge Infrastructure, WanFang Data, China Science and Technology Journal Database, and clinical trial register platforms from inception to 15 February 2022. We included randomized clinical trials that evaluated the efficacy and safety of prophylactic antibiotics. Primary outcomes were mortality rate and incidence of pneumonia. The pooled risk ratio (RR) and mean differences with 95% confidence interval (CI) were calculated using the random or fixed-effect model depending on heterogeneity. The quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: Twelve studies (4809 participants) were included. There was no significant difference in the mortality rate (12 trials, n = 4740, RR 1.03 [95% Cl: 0.91-1.16], high-quality evidence), incidence of pneumonia (7 trials, n = 4352, RR 0.94 [95% CI: 0.79-1.11], high-quality evidence) and the incidence of adverse events between the prophylactic antibiotics and control groups. Prophylactic antibiotics significantly reduced the incidence of infections (8 trials, n = 4517, RR 0.72 [95% CI: 0.58-0.89], moderate-quality evidence) and urinary tract infections (7 trials, n = 4352, RR 0.39 [95% CI: 0.3-0.49], moderate-quality evidence). None of the subgroup analyses showed a significant difference in mortality or the incidence of pneumonia. CONCLUSION: For acute stroke patients, prophylactic antibiotics were significantly associated with fewer incidences of any infections and urinary tract infections without significant differences in mortality rate and pneumonia.

Mitigating end-to-end nonlinearity in LED-based VLC transceivers via optical intensity feedback: erratum.

We present an erratum to our Letter [Opt. Lett.47, 3688 (2022)10.1364/OL.463637]. This erratum corrects subscript errors in Eq. (1), H1 and H2. These errors could confuse readers when they perform the derivation processes, but the errors do not affect our experimental results. Therefore, these corrections do not affect the results and conclusions of the original Letter.

Mitigating end-to-end nonlinearity in LED-based VLC transceivers via an optical intensity feedback.

This Letter proposes a novel, to the best of our knowledge, intensity-modulation transmitter equipped with an optical intensity feedback (OIF) loop, which mitigates the holistic nonlinearity on both sides of intensity modulation and direct detection (IM/DD) transceivers from solely the transmitter side. In contrast to the recent effort on pre-distortion, we construct a negative feedback loop bridging the optical intensity of light-emitting diodes (LEDs) toward a sensor for nonlinearity perception to suppress the nonlinearity among all physical devices. In the meantime, we propose an analytical model for the feedback loop and an implementation scheme. The experimental results demonstrate a significant linearity improvement in the total harmonic distortion (THD) and the power gain flatness. More specifically, the average THD of the bipolar junction transistor (BJT)-based OIF transceiver is -49.4 dB (0.37%) and the minimum power gain variance is 0.0005, 0.0025% of the control group. As for the transceiver using a metal-oxide-semiconductor field-effect transistor (MOSFET), its average THD is -52.42 dB (0.25%) and the minimum power gain variance can reach 0.0026. Not only that, since the method only takes advantage of the negative feedback feature and dose not rely on any particular module, it has lower complexity and better applicability.

Fabrication of ZnO@Plant Polyphenols/Cellulose as Active Food Packaging and Its Enhanced Antibacterial Activity.

To investigate the efficient use of bioresources and bioproducts, plant polyphenol (PPL) was extracted from larch bark and further applied to prepare ZnO@PPL/Cel with cellulose to examine its potential as an active package material. The structure and morphology were fully characterized by XRD, SEM, FTIR, XPS and Raman spectra. It was found that PPL is able to cover ZnO and form a coating layer. In addition, PPL cross-links with cellulose and makes ZnO distribute evenly on the cellulose fibers. Coating with PPL creates a pinecone-like morphology in ZnO, which is constructed by subunits of 50 nm ZnO slices. The interactions among ZnO, PPL and cellulose have been attributed to hydrogen bonding, which plays an important role in guiding the formation of composites. The antibacterial properties against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) were tested by the inhibition zone method. Our composite ZnO@PPL/Cel has superior antibacterial activity compared to ZnO/Cel. The antibacterial mechanism has also been elaborated on. The low cost, simple preparation method and good performance of ZnO@PPL/Cel suggest the potential for it to be applied as active food packaging.

CTRL: Closed-Loop Transcription to an LDR via Minimaxing Rate Reduction.

This work proposes a new computational framework for learning a structured generative model for real-world datasets. In particular, we propose to learn a Closed-loop Transcriptionbetween a multi-class, multi-dimensional data distribution and a Linear discriminative representation (CTRL) in the feature space that consists of multiple independent multi-dimensional linear subspaces. In particular, we argue that the optimal encoding and decoding mappings sought can be formulated as a two-player minimax game between the encoder and decoderfor the learned representation. A natural utility function for this game is the so-called rate reduction, a simple information-theoretic measure for distances between mixtures of subspace-like Gaussians in the feature space. Our formulation draws inspiration from closed-loop error feedback from control systems and avoids expensive evaluating and minimizing of approximated distances between arbitrary distributions in either the data space or the feature space. To a large extent, this new formulation unifies the concepts and benefits of Auto-Encoding and GAN and naturally extends them to the settings of learning a both discriminative and generative representation for multi-class and multi-dimensional real-world data. Our extensive experiments on many benchmark imagery datasets demonstrate tremendous potential of this new closed-loop formulation: under fair comparison, visual quality of the learned decoder and classification performance of the encoder is competitive and arguably better than existing methods based on GAN, VAE, or a combination of both. Unlike existing generative models, the so-learned features of the multiple classes are structured instead of hidden: different classes are explicitly mapped onto corresponding independent principal subspaces in the feature space, and diverse visual attributes within each class are modeled by the independent principal components within each subspace.

Hepatotoxicity with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer patients: A network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: The efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients diagnosed with non-small-cell lung cancer (NSCLC) has been confirmed by a large number of studies. However, hepatotoxicity caused by EGFR-TKIs has not been widely investigated. This review compares the hepatotoxicity of different EGFR-TKIs through a network meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were systematically searched from their individual inceptions to 20 May 2020 with the goal of identifying randomized controlled trials (RCTs) reporting hepatotoxicity in NSCLC patients receiving EGFR-TKIs. A random-effects pairwise meta-analysis and network meta-analysis were performed within a frequentist framework. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Twelve eligible RCTs, including data from 6,280 patients diagnosed with NSCLC, were analysed. In our network meta-analysis, gefitinib was associated with a higher risk for hepatotoxicity compared to placebo (RR, 2.55; 95% CI, 1.32-4.89) and dacomitinib (RR, 2.60; 95% CI, 1.30-5.20) in terms of all-grades alanine transaminase (ALT) elevation. As for all-grades aspartate transaminase (AST) elevation, gefitinib and erlotinib showed a significantly increased risk for hepatotoxicity compared to afatinib, dacomitinib and placebo (erlotinib vs. afatinib: RR, 1.85; 95% CI, 1.05-3.24; erlotinib vs. dacomitinib: RR, 1.68; 95% CI, 1.19-2.36; erlotinib vs. placebo: RR, 3.38; 95% CI, 1.69-6.73; gefitinib vs. afatinib: RR, 2.23; 95% CI, 1.32-3.79; gefitinib vs. dacomitinib: RR, 2.03; 95% CI, 1.51-2.73; gefitinib vs. placebo: RR, 4.08; 95% CI, 2.11-7.91). There was a high risk of high-grade ALT elevation in patients treated with gefitinib compared to patients treated with erlotinib (RR, 4.31; 95% CI, 2.15-8.66), dacomitinib (RR, 6.95; 95% CI, 1.85-26.05) or placebo (RR, 8.38; 95% CI, 1.56-45.01). No statistically significant differences were identified among the five agents analysed in terms of all-grades TB elevation and high-grade AST elevation. The surface under the cumulative ranking curve (SUCRA) revealed that gefitinib showed a potentially higher risk for ALT and AST elevation compared to other EGFR-TKIs regardless of grade. WHAT IS NEW AND CONCLUSION: Current evidence indicates that the association between afatinib or dacomitinib and risk of liver enzyme elevation remains uncertain in patients diagnosed with NSCLC. Some evidence suggests that gefitinib and erlotinib may be associated with a significantly increased risk for hepatotoxicity in patients with NSCLC. However, given that the elevation of liver enzymes was not definitely associated with EGFR-TKIs and publication bias, further studies are required to confirm these results.

The impact of smoking status on the progression-free survival of non-small cell lung cancer patients receiving molecularly target therapy or immunotherapy versus chemotherapy: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Smoking has a notable influence on the efficacy of medications for lung cancer. Previous studies illustrated the correlation between smoking and the efficacy of first-line Epidermal Growth Factor Receptors-Tyrosine Kinase Inhibitors (EGFR-TKIs). The benefit of smokers in immunotherapy was still controversial. Here, we investigated the impact of smoking on clinical outcomes of molecularly targeted therapies or immunotherapy in Non-Small Cell Lung Cancer (NSCLC). METHODS: We performed meta-analysis including trials comparing EGFR-TKIs, Anaplastic Lymphoma Kinase (ALK) inhibitors or Immune Checkpoint Inhibitors (ICIs) against chemotherapy in NSCLC. The Progression-Free Survival (PFS)-Hazard Ratios (HRs) of two groups served as the index and we used random effects to pool outcomes. RESULTS AND DISCUSSION: Twenty randomized trials were selected. Compared with chemotherapy, treatment with EGFR-TKIs had similar benefit in never-smokers (PFS: HR = 0.46, 95% CI 0.30 to 0.69) and smokers (PFS: HR = 0.68, 95% CI 0.50 to 0.91; p = 0.135) while non-smokers (PFS: HR = 0.32, 95% CI 0.23 to 0.44) had better benefit from first-line EGFR-TKIs than smokers (PFS: HR = 0.54, 95% CI 0.41 to 0.71; p = 0.02). Treatment with ALK inhibitors had similar benefits in never-smokers (PFS: HR = 0.43, 95% CI 0.35 to 0.53) and smokers (PFS: HR = 0.56, 95% CI 0.44 to 0.71; p = 0.406). The benefit of ICIs in smokers (PFS: HR = 0.79, 95% CI 0.64 to 0.98) was significantly greater than never-smokers (PFS: HR = 1.81, 95% CI 1.27 to 2.57; p = 0.004). WHAT IS NEW AND CONCLUSION: Smoking status is an important clinical predictor of therapy in NSCLC. Never-smokers and smokers have similar benefit with EGFR-TKIs therapy compared with chemotherapy, while never-smokers have greater benefit after first-line EGFR-TKIs therapy. There was similar benefit in never-smokers and smokers when using ALK inhibitors over chemotherapy. Additionally, ICIs treatment over chemotherapy leads to more favourable PFS in smokers both in first-line and second-line settings.

Efficacy and safety of antiviral treatment for COVID-19 from evidence in studies of SARS-CoV-2 and other acute viral infections: a systematic review and meta-analysis.

BACKGROUND: Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes. RESULTS: In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting. INTERPRETATION: To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

Modulation index dependence of intensity modulation bandwidth in visible light communications.

The modulation bandwidth of a light-emitting diode is inversely proportional to the carrier lifetime, which changes with varying injected current. However, in conventional implementations of visible light communications, the influence of bias current is always emphasized, while the effects of modulation indices and signal components are ignored. In this Letter, it is the first time, to the best of our knowledge, that the mechanism on how modulated signal components impact modulation bandwidth is clarified. We reveal and interpret this impact by featuring the response at different modulation indices and intensity distributions mathematically and experimentally, proposing a series of theoretical approaches for the insight of modulation at a high index. This Letter donates a novel perspective on deciding appropriate configurations for modulators according to the modulation characteristics at a high index of the input signal.

Optimized DFT-spread OFDM based visible light communications with multiple lighting sources.

Discrete Fourier transform spread orthogonal frequency-division multiplexing (DFT-S-OFDM) has demonstrated its capability in reducing peak to average ratio (PAPR), while maintaining reliable transmissions. This paper investigates the application of DFT-S-OFDM technology in visible light communications (VLC), and reveals the mechanism on how a multiple lighting distributed layout affects its performance. In addition, an optimization approach of lighting layout is proposed through making a trade-off between the strong interfered areas and the maximum delay spread inside. Eventually, a Gbit/s DFT-S-OFDM based multiple lighting VLC downlink prototype is achieved for the first time in the form of real-time baseband modem and compact size components.

Efficacité et innocuité des agents antiviraux contre le SRAS-CoV-2, selon des données d'études sur la COVID-19 et d'autres infections virales aiguës : revue systématique et méta-analyse.

CONTEXTE: On donne de façon empirique des agents antiviraux à certains patients atteints de la maladie à coronavirus 2019 (COVID-19). Dans le but d'appuyer la rédaction de lignes directrices sur la prise en charge de la COVID-19, nous avons réalisé une revue systématique des bénéfices et des préjudices associés à 7 traitements antiviraux contre cette infection. MÉTHODES: Nous avons effectué des recherches dans MEDLINE, Embase, le Cochrane Central Register of Controlled Trials (CENTRAL), PubMed et 3 bases de données chinoises (CNKI, Wanfang Data et SinoMed) jusqu'au 19 avril 2020, dans medRxiv et ChinaXiv jusqu'au 27 avril 2020, ainsi que dans Chongqing VIP jusqu'au 30 avril 2020. Nous avons sélectionné des études sur la ribavirine, la chloroquine, l'hydroxychloroquine, l'umifénovir (Arbidol), le favipiravir, l'interféron et le lopinavir/ritonavir. Lorsqu'il n'y avait pas de données directes d'études sur la COVID-19, nous avons retenu des données indirectes d'études sur le syndrome respiratoire aigu sévère (SRAS) et le syndrome respiratoire du Moyen-Orient (SRMO) pour l'analyse de l'efficacité, et d'études sur d'autres infections respiratoires virales aiguës pour l'analyse de l'innocuité. RÉSULTATS: Le taux de décès chez les patients atteints d'une forme sans signe clinique de gravité de COVID-19 était extrêmement bas, ce qui ne permet pas de conclure à un effet important sur la mortalité. Nous n'avons obtenu que des données de très faible qualité indiquant que la plupart des traitements avaient peu ou pas de bénéfices sur les paramètres à l'étude, quelle que soit la gravité de la COVID-19. Seule exception : le traitement au lopinavir/ritonavir, pour lequel nous avons obtenu des données de faible qualité faisant état d'une réduction de la durée du séjour en unité de soins intensifs (différence des risques [DR] 5 jours de moins, intervalle de confiance [IC] de 95 % 0 à 9 jours) et de la durée d'hospitalisation (DR 1 jour de moins, IC de 95 % 0 à 2 jours). En ce qui concerne l'innocuité, les données étaient de faible ou de très faible qualité, sauf pour le traitement au lopinavir/ritonavir, où des données de qualité moyenne laissaient supposer une augmentation probable de la diarrhée, des nausées et des vomissements. INTERPRÉTATION: À l'heure actuelle, rien ne prouve de façon convaincante que les traitements antiviraux apportent des bénéfices importants dans la lutte contre la COVID-19, bien que les données propres à chaque traitement n'excluent pas cette possibilité. D'autres essais randomisés et contrôlés menés auprès de patients atteints de la COVID-19 sont nécessaires avant de pouvoir recourir à ces traitements en toute confiance.

Bidirectional two-sample Mendelian randomization study of association between smoking initiation and atrial fibrillation.

INTRODUCTION: The relationship between smoking and heart disease has been frequently reported. Therefore, we aimed to explore the association between smoking initiation and atrial fibrillation. METHODS: Genetic association data pertaining to smoking initiation and atrial fibrillation were obtained from genome-wide association studies (GWAS). Phenotypically related single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Inverse-variance weighted (IVW), weighted median, Mendelian randomization (MR), Egger regression, simple mode, and weighted mode methods were employed to perform the MR study. The association between smoking initiation and atrial fibrillation was evaluated using odds ratios (OR) and 95% confidence intervals (CI). Cochran's Q test was employed to assess heterogeneity among instrumental variables, utilizing the IVW and MR-Egger methods. The Egger-intercept method was employed to test for horizontal pleiotropy, and the 'leave-one-out' method was utilized for sensitivity analysis. RESULTS: The MR results for the effect of smoking initiation on atrial fibrillation (IVW, OR=1.11; 95% CI: 1.02-1.20, p=0.013) supported an association between smoking initiation and an increased likelihood of atrial fibrillation. In total, 85 SNPs were extracted from the GWAS pooled data as instrumental variables. The MR-Egger method indicated an intercept close to 0 (Egger intercept= -0.005, p=0.371), suggesting no horizontal pleiotropy in the selected instrumental variables. The 'leave-one-out' sensitivity analysis demonstrated that the results were robust and that no instrumental variables significantly influenced the results. Reverse MR analysis indicated no effect of atrial fibrillation on smoking initiation (IVW, OR=1.00; 95% CI: 0.99-1.02, p=0.684). CONCLUSIONS: Smoking initiation has a significant impact on atrial fibrillation. However, atrial fibrillation did not influence smoking initiation. This study provides novel insights into the genetic relationships between smoking initiation and atrial fibrillation.

Tetrandrine alleviates oxaliplatin-induced mechanical allodynia via modulation of inflammation-related genes.

Oxaliplatin, a platinum-based chemotherapy drug, causes neuropathic pain, yet effective pharmacological treatments are lacking. Previously, we showed that tetrandrine (TET), with anti-inflammatory properties, reduces mechanical allodynia in nerve-injured mice. This study explores the effect of TET on oxaliplatin-induced mechanical allodynia and gene changes in mice. Male C57BL/6J mice received oxaliplatin intraperitoneally to induce mechanical allodynia. Post-treatment with TET or vehicle, the mechanical withdrawal threshold (WMT) was assessed using von Frey filaments. TET alleviated oxaliplatin-induced mechanical allodynia. RNA sequencing identified 365 differentially expressed genes (DEGs) in the Control vs. Oxaliplatin group and 229 DEGs in the Oxaliplatin vs. TET group. Pearson correlation analysis of co-regulated DEGs and inflammation-related genes (IRGs) revealed 104 co-regulated inflammation-related genes (Co-IRGs) (|cor| > 0.8, P < 0.01). The top 30 genes in the PPI network were identified. Arg2, Cxcl12, H2-Q6, Kdr, and Nfkbia were highlighted based on ROC analysis. Subsequently, Arg2, Cxcl12, Kdr, and Nfkbia were further verified by qRCR. Immune infiltration analysis indicated increased follicular CD4 T cell infiltration in oxaliplatin-treated mice, reduced by TET. Molecular docking showed strong binding affinity between TET and proteins encoded by Arg2, Cxcl12, Kdr, and Nfkbia. In summary, TET may alleviate oxaliplatin-induced peripheral neuropathy in clinical conditions.

Phytochemistry, pharmacology, toxicology and detoxification of Polygonum multiflorum Thunb.: a comprehensive review.

Background: Polygonum multiflorum Thunb. (PM), a kind of perennial plant, belongs to the genus Polygonum of the family polygonaceae.The dry root of PM (also called Heshouwu), is a traditional Chinese medicine, which has a series of functions and is widely used in clinic for hair lossing, aging, and insomnia. While, PM also has some toxicity, its clinical drug safety has been concerned. In this paper, the chemical components, toxic mechanisms and detoxification strategies of PM were reviewed in order to provide evidence for its clinical application. Materials and methods: We conducted a systematic review of published literature of PM, including English and Chinese databases, such as PubMed, Web of Science, CNKI, and Wanfang. Results: PM contains a variety of chemical compounds, including stilbenes, quinones, flavonoids, phospholipids, and has many pharmacological activities such as anti-aging, wound healing, antioxidant, and anti-inflammatory properties. The PE has certain therapeutic effect, and it has certain toxicity like hepatotoxicity, nephrotoxicity, and embryotoxicity at the same time, but.these toxic effects could be effectively reduced by processing and compatibility. Conclusion: It is necessary to further explore the pharmacological and toxicological mechanisms of the main active compounds of PE.This article provides scientific basis for the safe clinical application of PM.

A review of Aconiti Lateralis Radix Praeparata (Fuzi) for kidney disease: phytochemistry, toxicology, herbal processing, and pharmacology.

Background: Aconiti Lateralis Radix Praeparata, commonly known as Fuzi in. traditional Chinese medicine (TCM), is widely utilized in clinical practice despite its inherent toxicity. Since ancient times, TCM practitioners have explored various processing techniques to broaden its clinical applications and enhance its safety profile. This review aims to summarize the effects of processing on the chemical composition, toxicity, and pharmacological properties of Fuzi, as well as investigate potential underlying mechanisms. Methods: Data on phytochemistry, toxicology, pharmacology, and processing methods of Fuzi were gathered from the literature of electronic databases, including Web of Science, PubMed, and CNKI. Results: Fuzi contains over 100 kinds of chemical compounds, including alkaloids, flavonoids, and polysaccharides, among which alkaloids are the main active compounds. Diester-diterpenoid alkaloids are the main contributors to Fuzi's toxicity and have side effects on some organs, such as the heart, liver, kidneys, nervous system, and reproductive system. The chemical composition of aconite, particularly its alkaloid content, was changed by hydrolysis or substitution reaction during processing to enhance its efficacy and reduce its toxicity. Salted aconite could enhance the therapeutic efficacy of Fuzi in treating kidney diseases and influence its pharmacokinetics. Conclusion: Processing plays an important role in increasing the efficiency and decreasing toxicity of aconite. Further studies are needed to elucidate the changes of aconite before and after processing and the underlying mechanisms of these changes, thereby providing evidence for the clinical safety of drug use.

What are the benefits of therapeutic drug monitoring in the optimization of adalimumab therapy? a systematic review and meta-analysis up to 2022.

Aims: Persistent uncertainties exist surrounding the therapeutic drug monitoring (TDM) of adalimumab in clinical settings. To address these issues, we conducted a systematic review to assess the current evidence regarding the benefits of TDM for adalimumab. Methods: PubMed, EMBASE, and Cochrane Databases were searched from inception to October 2022. The trials regarding to the list three key questions were considered: 1) Could routine proactive TDM assist in improving outcomes in patients receiving adalimumab? 2) Could reactive TDM assist in guiding subsequent treatment strategies for patients with treatment failure to adalimumab? 3) Could TDM assist in informing dose reduction or discontinuation in patients with low disease activity or in remission treated with adalimumab? Two reviewers independently selected the studies and extracted the data. Meta-analysis was performed to calculate the relative risk (RR) and 95% confidence interval (CI). Results: A total of 9 studies was included in this review. For proactive TDM, meta-analysis indicated that proactive TDM (n = 163/257, 63.42%) showed no significant superiority over reactive TDM and/or conventional management (n = 336/606, 55.44%) in achieving and/or maintaining clinical remission by random effects model (RR: 1.24, 95% CI 0.98-1.58, I 2 = 73%). There were three studies that supporting the reactive TDM, low drug levels in the absence of anti-drug antibodies (ADA) strongly indicate the need for dose intensification, and infliximab is a feasible choice for patients with low drug levels and ADA positivity. While swapping to another class should be considered in patients with adequate drug levels. In addition, TDM can help clinicians optimize dosing schedules and prevent overtreatment in patients who have achieved low disease activity and sufficient drug concentrations, with no predictive value for successful adalimumab discontinuation. Conclusion: Current evidence suggests that proactive TDM is numerically but not statistically significant superiority over reactive TDM and/or conventional management. Reactive TDM can aid in understanding treatment failure and developing subsequent therapy. For patients reaching low disease activity and remission, TDM can help successful dose reduction, while it cannot inform the successful drug discontinuation. However, existing trials are limited, and more well-designed trials are necessary to clarify the role of TDM in adalimumab treatment.

Comprehensive analysis of risk factors (methanol, acetaldehyde and higher alcohols) in alcoholic beverages and their reduction strategies: GC-MS analysis and modified activated carbon adsorption and characterization.

This study endeavors to examine the levels of risk factors in alcoholic beverages and propose mitigation strategies. GC-MS analysis was utilized to assess risk factors in various distilled-spirits. The content of such risk factors in spirits ranked as follows: vodka ≈ gin < baijiu < whiskey < brandy, and all were adhering to the Chinese national standard. Additionally, a method was refined to alleviate these risks, employing various reagents for activated carbon modification and evaluating their adsorption efficiency for risk factors reduction. Oxalic acid-modified activated carbon exhibited promising adsorption rates for risk factors with acceptable flavor compounds loss, rendering it a prospective solution for health hazard reduction. Characterization via SEM and nitrogen-adsorption-desorption was conducted on the optimal material, complemented by sensory experiments to optimize its application. This study offers valuable insights into the content of risk factors in alcoholic beverages, aiding in improving quality and safety of alcoholic beverages.

Durable Photo-Pyroelectric Detection in a Diamine-Constructed Lead-Free Hybrid Perovskite Ferroelectric.

As a subcategory of pyroelectric materials, hybrid perovskite ferroelectrics possess substantial pyroelectric properties and exceptional light absorption characteristics, demonstrating significant potential in the photo-pyroelectric (PPE) detection field. Despite the significant advantages of hybrid perovskite ferroelectric materials for PPE detection, both the lead issue and the weak stability from van der Waals interactions in monoamines have hindered their further application. Here, 1D lead-free ferroelectric (BDA)SbBr5 (1, where BDA is 1,4-butanediammonium) is fabricated to achieve PPE detection. Compound 1 exhibits significant symmetry breaking attributed to the order-disorder transition of organic cations and octahedral distortions. Specifically, compound 1 enables broad-spectrum PPE detection from UV to near-infrared (377-980 nm) and further realizes switchable pyroelectric current after polarization. More importantly, the stability of the pyroelectric current is preserved without degradation over three months, attributed to the hydrogen bonding interactions of butanediamide. Further theoretical calculations of compound 1 reveal a more negative energy of formation than its monoamine homologs (BA)2SbBr5 (where BA is n-butylammonium), which is evidence of its stability. These findings highlight 1 as a promising candidate for high-stability and environmentally friendly PPE wide-spectrum detection, representing a noteworthy advancement in the ferroelectric field.