An Octacarboxylate-Linked Sodium Metal-Organic Framework with High Porosity.

Alkali metal-based metal-organic frameworks (MOFs) with permanent porosity are scarce because of their high tendency to coordinate with solvents such as water. However, these MOFs are lightweight and bear gravimetric benefits for gas adsorption related applications. In this study, we present the successful construction of a microporous MOF, designated as HIAM-111, built solely on sodium ions by using an octacarboxylate linker. The structure of HIAM-111 is based on 8-connected Na4 clusters and exhibits a novel topology with an underlying 32,42,8-c net. Remarkably, HAM-111 possesses a robust and highly porous framework with a BET surface area of 1561 m2/g, significantly surpassing that of the previously reported Na-MOFs. Further investigations demonstrate that HIAM-111 is capable of separating C2H2/CO2 and purifying C2H4 directly from C2H4/C2H2/C2H6 with high adsorption capacities. The current work may shed light on the rational design of robust and porous MOFs based on alkali metals.

A nuclear pore complex-associated regulation of SUMOylation in meiosis.

The nuclear pore complex (NPC) provides a permeable barrier between the nucleoplasm and cytoplasm. In a subset of NPC constituents that regulate meiosis in the fission yeast Schizosaccharomyces pombe, we found that nucleoporin Nup132 (homolog of human Nup133) deficiency resulted in transient leakage of nuclear proteins during meiosis I, as observed in the nup132 gene-deleted mutant. The nuclear protein leakage accompanied the liberation of the small ubiquitin-like modifier (SUMO)-specific ubiquitin-like protease 1 (Ulp1) from the NPC. Ulp1 retention at the nuclear pore prevented nuclear protein leakage and restored normal meiosis in a mutant lacking Nup132. Furthermore, using mass spectrometry analysis, we identified DNA topoisomerase 2 (Top2) and RCC1-related protein (Pim1) as the target proteins for SUMOylation. SUMOylation levels of Top2 and Pim1 were altered in meiotic cells lacking Nup132. HyperSUMOylated Top2 increased the binding affinity at the centromeres of nup132 gene-deleted meiotic cells. The Top2-12KR sumoylation mutant was less localized to the centromeric regions. Our results suggest that SUMOylation of chromatin-binding proteins is regulated by the NPC-bound SUMO-specific protease and is important for the progression of meiosis.

Incidence, characteristics, and risk factors of drug-associated muscle adverse reaction: a retrospective real-world study of inpatients.

OBJECTIVE: To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use. METHODS: We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses. RESULTS: Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs. CONCLUSION: Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life.

Time series-based hybrid ensemble learning model with multivariate multidimensional feature coding for DNA methylation prediction.

BACKGROUND: DNA methylation is a form of epigenetic modification that impacts gene expression without modifying the DNA sequence, thereby exerting control over gene function and cellular development. The prediction of DNA methylation is vital for understanding and exploring gene regulatory mechanisms. Currently, machine learning algorithms are primarily used for model construction. However, several challenges remain to be addressed, including limited prediction accuracy, constrained generalization capability, and insufficient learning capacity. RESULTS: In response to the aforementioned challenges, this paper leverages the similarities between DNA sequences and time series to introduce a time series-based hybrid ensemble learning model, called Multi2-Con-CAPSO-LSTM. The model utilizes multivariate and multidimensional encoding approach, combining three types of time series encodings with three kinds of genetic feature encodings, resulting in a total of nine types of feature encoding matrices. Convolutional Neural Networks are utilized to extract features from DNA sequences, including temporal, positional, physicochemical, and genetic information, thereby creating a comprehensive feature matrix. The Long Short-Term Memory model is then optimized using the Chaotic Accelerated Particle Swarm Optimization algorithm for predicting DNA methylation. CONCLUSIONS: Through cross-validation experiments conducted on 17 species involving three types of DNA methylation (6 mA, 5hmC, and 4mC), the results demonstrate the robust predictive capabilities of the Multi2-Con-CAPSO-LSTM model in DNA methylation prediction across various types and species. Compared with other benchmark models, the Multi2-Con-CAPSO-LSTM model demonstrates significant advantages in sensitivity, specificity, accuracy, and correlation. The model proposed in this paper provides valuable insights and inspiration across various disciplines, including sequence alignment, genetic evolution, time series analysis, and structure-activity relationships.

Signal peptide-CUB-EGF-like repeat-containing protein 1-promoted FLT3 signaling is critical for the initiation and maintenance of MLL-rearranged acute leukemia.

A hallmark of mixed lineage leukemia gene-rearranged (MLL-r) acute myeloid leukemia that offers an opportunity for targeted therapy is addiction to protein tyrosine kinase signaling. One such signal is the receptor tyrosine kinase Fms-like receptor tyrosine kinase 3 (FLT3) upregulated by cooperation of the transcription factors homeobox A9 (HOXA9) and Meis homeobox 1 (MEIS1). Signal peptide-CUB-EGF-like repeat-containing protein (SCUBE) family proteins have previously been shown to act as a co-receptor for augmenting signaling activity of a receptor tyrosine kinase (e.g., vascular endothelial growth factor receptor). However, whether SCUBE1 is involved in the pathological activation of FLT3 during MLL-r leukemogenesis remains unknown. Here we first show that SCUBE1 is a direct target of HOXA9/MEIS1 that is highly expressed on the MLL-r cell surface and predicts poor prognosis in de novo acute myeloid leukemia. We further demonstrate, by using a conditional knockout mouse model, that Scube1 is required for both the initiation and maintenance of MLL-AF9-induced leukemogenesis in vivo. Further proteomic, molecular and biochemical analyses revealed that the membrane-tethered SCUBE1 binds to the FLT3 ligand and the extracellular ligand-binding domains of FLT3, thus facilitating activation of the signal axis FLT3-LYN (a non-receptor tyrosine kinase) to initiate leukemic growth and survival signals. Importantly, targeting surface SCUBE1 by an anti-SCUBE1 monomethyl auristatin E antibody-drug conjugate led to significantly decreased cell viability specifically in MLL-r leukemia. Our study indicates a novel function of SCUBE1 in leukemia and unravels the molecular mechanism of SCUBE1 in MLL-r acute myeloid leukemia. Thus, SCUBE1 is a potential therapeutic target for treating leukemia caused by MLL rearrangements.

Separation of C2H2/C2H4/C2H6 and C2H2/CO2 in a Nitrogen-Rich Copper-Based Microporous Metal-Organic Framework.

The purification of industrially valuable C2H2 and C2H4 from multicomponent mixtures represents a crucial process in the chemical industry. In this study, we present a copper-based metal-organic framework (L-py-Cu) built on a nitrogen-rich organic linker that is capable of separating C2H2/C2H4/C2H6 and C2H2/CO2 mixtures, therefore producing highly pure C2H4 and C2H2, respectively. L-py-Cu exhibits favorable adsorption of C2H2 and C2H6 over C2H4 and thus achieves one-step C2H4 purification from C2H2/C2H4/C2H6 ternary mixtures, as verified by multicomponent breakthrough measurements. In addition, it can also extract C2H2 from C2H2/CO2 binary mixtures.

Bifunctional Supertetrahedral Chalcogenolate Cluster-Based Assembly Materials Constructed by a Photoactive Ligand.

The assembly of supertetrahedral chalcogenolate clusters (SCCs) and multifunctional organic linkers could lead to the formation of tunable structures and synergistic properties. Two SCC-based assembled materials (SCCAM-1 and -2) constructed by a triangular chromophore ligand, tris(4-pyridylphenyl)amine, were successfully synthesized and characterized. The SCCAMs demonstrate unusually long-lived afterglow at low temperatures (83 K) and efficient activities for the photocatalytic degradation of organic dye in water.

Analysis of clinical characteristics and automatic monitoring of drug-induced arrhythmias in 167,546 inpatients.

OBJECTIVE: The purpose of this study was to analyze the occurrence characteristics, clinical manifestations, medication distribution, and incidence of drug-induced arrhythmias in a real-world inpatient population. METHODS: According to the inclusion and exclusion criteria as well as the ADR evaluation criteria, we retrospectively evaluated hospitalized patients in 2019 using the arrhythmia module of the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II). A detailed analysis was performed on the demographic data, ADR manifestations, and medication distribution of 2097 patients with drug-induced arrhythmias and QT interval prolongation. RESULTS: Of the 167,546 hospitalized patients, there were 1809 cases of drug-induced arrhythmias, with an incidence of 1.08%. The ADRs in 45.35% of positive patients occurred within 3 days after medication administration, and 46.73% of the patients were 65 years old or older. The predominant ADRs identified in this study were extrasystole, tachycardia, and QT interval prolongation, of which the incidence was 0.20%. Levofloxacin was the most involved drug, and levofloxacin-associated rates of incidence of arrhythmia and QT interval prolongation were 1.24% and 0.44%, respectively. The risk factors for drug-induced arrhythmias were male sex, advanced age, emaciation, obesity, and underlying illnesses such as cardiovascular diseases, diabetes mellitus, cerebrovascular diseases, and hepatic and renal inadequacy (P < 0.05). CONCLUSION: The incidence of drug-induced arrhythmias was in the range of common, while QTc interval prolongation was occasional. It is necessary to pay attention to patients with risk factors.

Kelch-like proteins in the gastrointestinal tumors.

Gastrointestinal tumors have become a worldwide health problem with high morbidity and poor clinical outcomes. Chemotherapy and surgery, the main treatment methods, are still far from meeting the treatment needs of patients, and targeted therapy is in urgent need of development. Recently, emerging evidence suggests that kelch-like (KLHL) proteins play essential roles in maintaining proteostasis and are involved in the progression of various cancers, functioning as adaptors in the E3 ligase complex and promoting the specific degradation of substrates. Therefore, KLHL proteins should be taken into consideration for targeted therapy strategy discovery. This review summarizes the current knowledge of KLHL proteins in gastrointestinal tumors and discusses the potential of KLHL proteins as potential drug targets and prognostic biomarkers.

Upper limb manual training for children with cerebral palsy: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: There are different upper limb manual training protocols, namely constraint-induced movement therapy, modified constraint-induced movement therapy, hand-arm bimanual intensive training, hand-arm bimanual intensive training including lower extremity, action observation training, and mirror therapy, available for improving functional outcomes in children with cerebral palsy. However, the effect and priority of these strategies remain unclear. DATA SOURCES: We searched the PubMed, Cochrane Library, and Embase databases for relevant articles from inception to October 12, 2022. REVIEW METHODS: To assess the effect and priority of different strategies of upper limb manual training protocols through a systematic review and network meta-analysis of randomized controlled trials. RESULTS: We included 22 randomized controlled trials in this network meta-analysis. The ranking probability and standard mean differences with 95% credible intervals of the comparison between placebo and other forms of upper limb manual training were as follows: mirror therapy = 2.83 (1.78, 3.88), hand-arm bimanual intensive training including the lower extremity = 0.53 (0.09, 0.96), constraint-induced movement therapy = 0.44 (0.18, 0.71), hand-arm bimanual intensive training = 0.41 (0.15, 0.67), modified constraint-induced movement therapy = 0.39 (0.03, 0.74), and action observation training = 0.18 ( - 0.29, 0.65). No significant inconsistency was noted between the results of direct and indirect comparisons. CONCLUSION: We suggest that mirror therapy could be the upper limb manual training protocol of choice for improving functional outcomes in patients with cerebral palsy.

Host trehalose metabolism disruption by validamycin A results in reduced fitness of parasitoid offspring.

The general cutworm, Spodoptera litura (Lepidoptera: Noctuidae) is a worldwide destructive omnivorous pest and the endoparasitoid wasp Meteorus pulchricornis (Hymenoptera: Braconidae) is the dominant endoparasitoid of S. litura larvae. Trehalase is a key enzyme in insect trehalose metabolism and plays an important role in the growth and development of insects. However, the specific function of trehalase in parasitoid and host associations has been less reported. In this study, we obtained two trehalase genes (SlTre1 and SlTre2) from our previously constructed S. litura transcriptome database; they were highly expressed in 3rd instar larvae. SlTre1 was mainly expressed in the midgut, and SlTre2 was expressed highest in the head. SlTre1 and SlTre2 were highly expressed 5 days after parasitization by M. pulchricornis. Treatment with the trehalase inhibitor validamycin A significantly inhibited the expression levels of SlTre1 and SlTre2, and the trehalase activity. Besides, the content of trehalose was increased but the content of glucose was decreased 24 h after validamycin A treatment in parasitized S. litura larvae. In addition, the immune-related genes in phenoloxidase (PO) pathway and fatty acid synthesis-related genes in lipid metabolism were upregulated in parasitized host larvae after validamycin A treatment. Importantly, the emergence rate, proportion of normal adults, and body size of parasitoid offspring was decreased in parasitized S. litura larvae after validamycin A treatment, indicating that validamycin A disrupts the trehalose metabolism of parasitized host and thus reduces the fitness of parasitoid offspring. The present study provides a novel perspective for coordinating the application of biocontrol and antibiotics in agroecosystem.

Identification and functional study of detoxification-related genes in response to tolfenpyrad stress in Glyphodes pyloalis Walker (Lepidoptera: Pyralidae).

Glyphodes pyloalis Walker (G. pyloalis) is a common destructive mulberry pest. Due to the long-term and frequent use of insecticides, it has developed tolerance to commonly used insecticides. Tolfenpyrad (TFP) is a novel pyrazole heterocyclic insecticide. In order to understand the TFP detoxification mechanism of G. pyloalis larvae, we first estimated the LC30 dose of TFP for 3rd instar G. pyloalis larvae. Next, we identified genes that were differentially expressed in 3rd instar G. pyloalis larvae treated with TFP compared to the control group by transcriptome sequencing. In total, 86,949,569 and 67,442,028 clean reads were obtained from TFP-treated and control G. pyloalis larvae, respectively. A total of 5588 differentially expressed genes (DEGs) were identified in TFP-treated and control G. pyloalis larvae, of which 3084 genes were upregulated and 2504 genes were downregulated. We analyzed the expression of 43 candidate detoxification enzyme genes associated with insecticide tolerance using qPCR. According to the spatiotemporal expression pattern of DEGs, we found that CYP6ABE1, CYP333A36 and GST-epsilon8 were highly expressed in the midgut, while CarEs14 was strongly expressed in haemolymph. Furthermore, we successfully knocked down these genes by RNA interference. After silencing CYP6ABE1 and CYP333A36, bioassay showed that the mortality rate of TFP-treated G. pyloalis larvae was significantly higher compared to the control group. This study provides a theoretical foundation for understanding the sensitivity of G. pyloalis to TFP and establish the basis for the effective and green management of this pest.

Radiofrequency ablation is an inferior option to liver resection for solitary hepatocellular carcinoma ≤ 5 cm without cirrhosis: A population-based study with stratification by tumor size.

BACKGROUND: About 10%-20% of all individuals who develop hepatocellular carcinoma (HCC) do not have cirrhosis. Comparisons are rarely reported regarding the effectiveness of radiofrequency ablation (RFA) and liver resection (LR) in survival of HCC without cirrhosis and stratification by tumor size ≤ 5 cm. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database and identified 1505 patients with a solitary HCC tumor ≤ 5 cm who underwent RFA or LR during 2004-2015. Patients were classified into non-cirrhosis and cirrhosis groups and each group was categorized into three subgroups, according to tumor size (≤ 30 mm, 31-40 mm, 41-50 mm). RESULTS: In patients without cirrhosis, LR showed better 5-year HCC cancer-specific survival than RFA in all tumor size subgroups (≤ 30 mm: 82.51% vs. 56.42%; 31-40 mm: 71.31% vs. 46.83%; 41-50 mm: 74.7% vs. 37.5%; all P < 0.05). Compared with RFA, LR was an independent protective factor for HCC cancer-specific survival in multivariate Cox analysis [≤ 30 mm: hazard ratio (HR) = 0.533, 95% confidence interval (CI): 0.313-0.908; 31-40 mm: HR = 0.439, 95% CI: 0.201-0.957; 41-50 mm: HR = 0.382; 95% CI: 0.159-0.916; all P < 0.05]. In patients with cirrhosis, for both tumor size ≤ 30 mm and 31-40 mm groups, there were no significant survival differences between RFA and LR in multivariate analysis (all P > 0.05). However, in those with tumor size 41-50 mm, LR showed significantly better 5-year HCC cancer-specific survival than RFA in both univariate (54.72% vs. 23.06%; P < 0.001) and multivariate analyses (HR = 0.297; 95% CI: 0.136-0.648; P = 0.002). CONCLUSIONS: RFA is an inferior treatment option to LR for patients without cirrhosis who have a solitary HCC tumor ≤ 5 cm.

Comparison of the Clinical Effect of Double Eyelid Blepharoplasty with the Orbital Septum Method and the Classical Method.

OBJECTIVE: To observe the clinical effect between orbital septum incision and classical incision of double eyelid plasty. METHODS: We retrospectively analyzed 381 patients who underwent double eyelid blepharoplasty in the Department of Plastic and Laser Cosmetology of Hunan Provincial People's Hospital from January 2019 to December 2019. The patients were divided into two groups according to different surgical methods: group A (n = 146) received the classical method and group B (n = 235) received the orbital septum method. The incidence of early postoperative complications, scar depression from 6 months to 1 year after the operation, the condition of 'meat strip' (the accumulation of soft tissue in front of the tarsal plate after double eyelid surgery, including skin, muscle, and fascia fat, results in a hypertrophic appearance of the upper eyelid) below the double eyelid line, and the symmetry of double eyelids were analyzed and evaluated. RESULTS: The total number of early postoperative complications in group A was seven cases (incidence rate: approximately 4.80%), and the total number of early postoperative complications in group B was two cases (incidence rate: approximately 0.85%), with a statistically significant difference (P < 0.05). The degree of scar depression in group B was significantly lighter than that in group A from 6 months to 1 year after the operation (P < 0.05). The score of 'meat strip' below the double eyelid line in group B was significantly lighter than that in group A (P < 0.05). The symmetry of double eyelids in group B was better than that in group A (P < 0.05) CONCLUSION: Compared to the classical double eyelid method, the orbital septum method has the advantages of reducing early postoperative complications, reducing the severity of the scar, slighting the 'meat strip,' and improving symmetry, which results in higher postoperative satisfaction LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Linker Vacancy Engineering of a Robust ftw-type Zr-MOF for Hexane Isomers Separation.

Discrimination of physically similar molecules by porous solids represents an important yet challenging task in industrially relevant chemical separations. Precisely controlled pore dimension and/or tailored pore surface functionality are crucial to achieve high-efficiency separation. Metal-organic frameworks (MOFs) are promising candidates for these challenging separations in light of their structural diversity as well as highly adjustable pore dimension/functionality. We report here a microporous, ftw-type Zr-based MOF structure, HIAM-410 (HIAM=Hoffmann Institute of Advanced Materials), built on hexanuclear Zr6 cluster and pyrene-1,3,6,8-tetracarboxylate (ptc4- ). Its crystallographic structure has been determined using continuous rotation electron diffraction (cRED) technique combined with Rietveld refinement against powder X-ray diffraction data, aided by low-dose high-resolution transmission electron microscopy (HRTEM) imaging. The compound features exceptional framework stability that is comparable to the prototype MOF UiO-66. Interestingly, the linker vacancies in the pristine MOF structure could be partially restored by post-synthetic linker insertion. Its separation capability of hexane isomers is enhanced substantially upon the linker vacancy engineering. The restored structure exhibits efficient splitting of monobranched and dibranched hexane isomers at both room temperature and industrially relevant temperature.

HiCmapTools: a tool to access HiC contact maps.

BACKGROUND: With the development of HiC technology, more and more HiC sequencing data have been produced. Although there are dozens of packages that can turn sequencing data into contact maps, there is no appropriate tool to query contact maps in order to extract biological information from HiC datasets. RESULTS: We present HiCmapTools, a tool for biologists to efficiently calculate and analyze HiC maps. The complete program provides multi-query modes and analysis tools. We have validated its utility on two real biological questions: TAD loop and TAD intra-density. CONCLUSIONS: HiCmapTools supports seven access options so that biologists can quantify contact frequency of the interest sites. The tool has been implemented in C++ and R and is freely available at https://github.com/changlabtw/hicmaptools and documented at https://hicmaptools.readthedocs.io/ .

Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness.

BACKGROUND: We recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-ß receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown. METHOD: We performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, ingenuity pathway analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA (Lens culinaris agglutinin) blotting and LC-MS/MS (liquid chromatography-tandem mass spectrometry) analysis. RESULTS: Loss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity pathway analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvß5 or IL6ST might be crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial-mesenchymal transition and metastasis. CONCLUSIONS: Our report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis.

Carrier Free O2 -Economizer for Photodynamic Therapy Against Hypoxic Tumor by Inhibiting Cell Respiration.

Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to economize O2 for enhanced PDT against hypoxic tumors. The carrier-free O2 -economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self-assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self-delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier-free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment.

Efficacy and Safety of Multiple Dupilumab Dose Regimens in Patients with Moderate-To-Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Dupilumab ameliorates the signs and symptoms of atopic dermatitis (AD) and improves the patient's quality of life. Multiple-dose regimens of dupilumab have been applied by clinicians, but the efficacy of some regimens remains unclear. OBJECTIVES: The aim of the study was to systematically evaluate the efficacy and safety of multiple dupilumab dose regimens in patients with moderate-to-severe AD in terms of comprehensive outcomes. METHODS: We searched electronic databases and subjected the selected studies to risk-of-bias assessment and network meta-analysis (NMA). Efficacy and safety outcomes were compared using a random-effects NMA to estimate pooled relative risk ratio (RR) of direct and indirect comparisons among multiple dupilumab dose regimens. The Eczema Area Severity Index, Investigator's Global Assessment, and pruritus numerical rating scale were analyzed to assess the efficacy, while adverse events (AEs) and serious adverse events to represent the safety. RESULTS: Eight randomized controlled trials involving 3,679 patients were identified. Most patients received therapy for 16 weeks. Multiple dupilumab dose regimens, including 300 mg weekly (QW), 300 mg every 2 weeks (Q2W), 200 mg Q2W, 300 mg monthly (QM), 300 mg every 2 months (Q2M), and 100 mg QM were analyzed. All regimens, except 100 mg QM, had significantly better efficacy than placebo. 300 mg QW and 300 mg Q2W appeared to have similar efficacy. Notably, both 300 mg QW and 300 mg Q2W had no significantly better efficacy than 300 mg QM. As for 300 mg Q2M, significantly reduced efficacy was noted in only one efficacy outcome when compared to 300 mg QW and 300 mg Q2W. In terms of safety outcomes, AEs occurring with any of the regimens were comparable with the placebo. No significant inconsistency was noted within the network in all efficacy outcomes. CONCLUSIONS: Our NMA indicated that the administration of the following dupilumab regimens was effective for patients with moderate-to-severe AD: 300 mg QW, 300 mg Q2W, 200 mg Q2W, 300 mg QM, and 300 mg Q2M. Our data can improve the understanding of the relative efficacy and safety of multiple dupilumab dose regimens, which will help in shared decision-making between clinicians and patients.

Sublethal effects of organophosphorus insecticide phoxim on patch time allocation and oviposition behavior in a parasitoid wasp Meteorus pulchricornis.

Parasitoid wasps are key agents for controlling insect pests in integrated pest management programs. Although many studies have revealed that the behavior of parasitic wasps can be influenced by insecticides, the strategies of patch time allocation and oviposition have received less attention. In the present study, we forced the endoparasitoid Meteorus pulchricornis to phoxim exposure at the LC30 and tested the foraging behavior within patches with different densities of the host, the larvae of the tobacco cutworm Spodoptera litura. The results showed that phoxim treatment can significantly increase the patch-leaving tendency of female wasps, while host density had no impact. The number of oviposition and the number of previous patch visits also significantly influenced the patch time allocation decisions. The occurrence of oviposition behavior was negatively affected by phoxim exposure; however, progeny production was similar among patches with different host densities. Phoxim exposure shaped the offspring fitness correlates, including longer durations from cocoon to adult wasps, smaller body size, and shorter longevity. The findings of the present study highlight the sublethal effects that reduce the patch residence time and the fitness of parasitoid offspring, suggesting that the application of phoxim in association with M. pulchricornis should be carefully schemed in agroecosystems.