Seco-cyclic phorbol derivatives and their anti-HIV-1 activities.

Phorbol esters are recognized for their dual role as anti-HIV-1 agents and as activators of protein kinase C (PKC). The efficacy of phorbol esters in binding with PKC is attributed to the presence of oxygen groups at positions C20, C3/C4, and C9 of phorbol. Concurrently, the lipids located at positions C12/C13 are essential for both the anti-HIV-1 activity and the formation of the PKC-ligand complex. The influence of the cyclopropane ring at positions C13 and C14 in phorbol derivatives on their anti-HIV-1 activity requires further exploration. This research entailed the hydrolysis of phorbol, producing seco-cyclic phorbol derivatives. The anti-HIV-1 efficacy of these derivatives was assessed, and the affinity constant (Kd) for PKC-δ protein of selected seco-cyclic phorbol derivatives was determined through isothermal titration calorimetry. The findings suggest that the chemical modification of cyclopropanols could affect both the anti-HIV-1 activity and the PKC binding affinity. Remarkably, compound S11, with an EC50 of 0.27 µmol·L-1 and a CC50 of 153.92 µmol·L-1, demonstrated a potent inhibitory effect on the intermediate products of HIV-1 reverse transcription (ssDNA and 2LTR), likely acting at the viral entry stage, yet showed no affinity for the PKC-δ protein. These results position compound S11 as a potential candidate for further preclinical investigation and for studies aimed at elucidating the pharmacological mechanism underlying its anti-HIV-1 activity.

Genetic Causal Relationship Between Alanine Aminotransferase Levels and Risk of Gestational Diabetes Mellitus: Mendelian Randomization Analysis Based on Two Samples.

Gestational diabetes mellitus (GDM) is a frequent complication of pregnancy. The specific mechanisms underlying GDM have not yet been fully elucidated. Contemporary research indicates a potential association between liver enzyme irregularities and an increased risk of metabolic disorders, including diabetes. The alanine aminotransferase (ALT) level is recognized as a sensitive marker of liver injury. An increase in ALT levels is hypothesized to be linked to the pathogenesis of insulin resistance and diabetes. Nonetheless, the definitive causal link between ALT levels and GDM still needs to be determined. This investigation utilized two-sample Mendelian randomization (MR) to examine the genetic causation between alanine aminotransferase (ALT) and GDM. We acquired alanine aminotransferase (ALT)-related GWAS summary data from the UK Biobank, Million Veteran Program, Rotterdam Study, and Lifeline Study. Gestational diabetes data were obtained from the FinnGen Consortium. We employed various MR analysis techniques, including inverse-variance weighted (IVW), MR Egger, weighted median, simple, and weighted weighting. In addition to MR-Egger intercepts, Cochrane's Q test was also used to assess heterogeneity in the MR data, and the MR-PRESSO test was used to assess horizontal pleiotropy. To assess the association's sensitivity, a leave-one-out approach was employed. The IVW results confirmed the independent risk factor for GDM development, as indicated by the ALT level (p = .011). As shown by leave-one-out analysis, horizontal pleiotrophy did not significantly skew the causative link (p > .05). Our dual-sample MR analysis provides substantiated evidence of a genetic causal relationship between alanine aminotransferase (ALT) levels and gestational diabetes.

Comparison of the efficacy and safety of sodium valproate versus levetiracetam in the treatment of severe traumatic brain injury.

OBJECTIVE: To observe the efficacy and safety of sodium valproate (VPA) compared to levetiracetam (LEV) in the treatment of severe traumatic brain injury (sTBI). METHODS: In this blind, prospective study, eighty-four sTBI patients who had craniotomy from August 2021 to August 2023 were randomly split into two groups through random number table method: LEV and VPA, each with 42 patients. Both received comprehensive treatment post-craniotomy. LEV group: LEV injection on surgery day, transitioning to LEV tablets from day two. VPA group: VPA injection on surgery day, switching to VPA extended-release tablets from day two. The study compared hospital stay, neurological function, clinical outcomes, seizures, and drug reactions between groups. RESULTS: The length of hospital stay showed no significant difference between the LEV and VPA groups. Both groups demonstrated improved neurological function post-treatment (NIHSS and BI scores), with no significant between-group differences. Clinical outcomes at 3 months post-treatment were similar in both groups. Seizure occurrence within 3 months after treatment showed no significant difference between the LEV (19.05%) and VPA (23.81%) groups. However, the VPA group experienced a significantly higher rate of drug-related adverse reactions (40.48%) compared to the LEV group (21.43%). CONCLUSION: Both VPA and LEV are effective in treating sTBI, showing no significant difference in improving neurological function, daily life abilities, treatment outcomes, and seizure occurrence. However, VPA treatment exhibited a significantly higher incidence of drug-related adverse reactions compared to LEV, indicating that LEV might be a safer option for sTBI treatment.

Symbiotic Bacterial Communities of Insects Feeding on the Same Plant Lineage: Distinct Composition but Congruent Function.

The health and diversity of plant-feeding insects are strictly linked to their host plants and mutualistic symbionts. However, the study of bacterial symbionts within different insects on the same plant lineage is very limited. This study aimed to investigate the bacterial diversity in insect samples that exclusively feed on Bambusa, representing three insect orders, Hemiptera, Lepidoptera, and Blattodea, each exhibiting distinct dietary preferences. The bacterial community was predominantly composed of Proteobacteria, Spirochaetota, Cyanobacteria, Firmicutes, and Bacteroidota. The study found significant variations in symbiotic organisms among three insect orders: hemipterans had Buchnera, lepidopterans had Acinetobacter, and blattodean had Treponema. Furthermore, the dietary preferences of these insects played a pivotal role in shaping the symbiotic relationship of insects. Proteobacteria are prevalent in sap feeders, Spirochaetota dominate in stem feeders, and Cyanobacteria are abundant in leaf feeders. Seasonal influences also affect bacterial symbionts in P. bambucicola, with Serratia present exclusively in winter. We also observed that the bacterial composition varies across all samples, but their core functions appear to be consistent. This highlights the complex relationship between host phylogeny and diet, with phylogeny being the primary driver, shaping adaptations to specialized diets.

Chemical inhibitors targeting histone methylation readers.

Histone methylation reader domains are protein modules that recognize specific histone methylation marks, such as methylated or unmethylated lysine or arginine residues on histones. These reader proteins play crucial roles in the epigenetic regulation of gene expression, chromatin structure, and DNA damage repair. Dysregulation of these proteins has been linked to various diseases, including cancer, neurodegenerative diseases, and developmental disorders. Therefore, targeting these proteins with chemical inhibitors has emerged as an attractive approach for therapeutic intervention, and significant progress has been made in this area. In this review, we will summarize the development of inhibitors targeting histone methylation readers, including MBT domains, chromodomains, Tudor domains, PWWP domains, PHD fingers, and WD40 repeat domains. For each domain, we will briefly discuss its identification and biological/biochemical functions, and then focus on the discovery of inhibitors tailored to target this domain, summarizing the property and potential application of most inhibitors. We will also discuss the structural basis for the potency and selectivity of these inhibitors, which will aid in further lead generation and optimization. Finally, we will also address the challenges and strategies involved in the development of these inhibitors. It should facilitate the rational design and development of novel chemical scaffolds and new targeting strategies for histone methylation reader domains with the help of this body of data.

Using natural language processing to analyze unstructured patient-reported outcomes data derived from electronic health records for cancer populations: a systematic review.

INTRODUCTION: Patient-reported outcomes (PROs; symptoms, functional status, quality-of-life) expressed in the 'free-text' or 'unstructured' format within clinical notes from electronic health records (EHRs) offer valuable insights beyond biological and clinical data for medical decision-making. However, a comprehensive assessment of utilizing natural language processing (NLP) coupled with machine learning (ML) methods to analyze unstructured PROs and their clinical implementation for individuals affected by cancer remains lacking. AREAS COVERED: This study aimed to systematically review published studies that used NLP techniques to extract and analyze PROs in clinical narratives from EHRs for cancer populations. We examined the types of NLP (with and without ML) techniques and platforms for data processing, analysis, and clinical applications. EXPERT OPINION: Utilizing NLP methods offers a valuable approach for processing and analyzing unstructured PROs among cancer patients and survivors. These techniques encompass a broad range of applications, such as extracting or recognizing PROs, categorizing, characterizing, or grouping PROs, predicting or stratifying risk for unfavorable clinical results, and evaluating connections between PROs and adverse clinical outcomes. The employment of NLP techniques is advantageous in converting substantial volumes of unstructured PRO data within EHRs into practical clinical utilities for individuals with cancer.

Synthesis and anti-HIV activities of phorbol derivatives.

In this study, 37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated, building upon our previous synthesis of 51 phorbol derivatives. 12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out, demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation. These derivatives exhibited a higher safety index compared with the positive control drug. Among them, 12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol, designated as compound 3c, exhibited the most potent anti-HIV-1 activity (EC50 2.9 nmol·L-1, CC50/EC50 11 117.24) and significantly inhibited the formation of syncytium (EC50 7.0 nmol·L-1, CC50/EC50 4891.43). Moreover, compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor. Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C (PKC). Therefore, compound 3c emerges as a potential candidate for developing new anti-HIV drugs.

Correction: Twitter and Facebook posts about COVID-19 are less likely to spread misinformation compared to other health topics.

[This corrects the article DOI: 10.1371/journal.pone.0261768.].

Palladium-Catalyzed C2-Selective Direct Arylation of Benzo[b]thiophene 1,1-Dioxides with Arylboronic Acids.

A novel oxidative cross-coupling of benzo[b]thiophene 1,1-dioxides with arylboronic acids was reported. The efficient reaction occurred at the C2-position via C-H activation, followed by Pd(II)-catalyzed arylation. Furthermore, a series of C2-arylated products with significant photoluminescence properties have been synthesized and characterized, which illustrates the potential applications of our method in the aggregation-induced emission field.

Partial Correspondence between Host Plant-Related Differentiation and Symbiotic Bacterial Community in a Polyphagous Insect.

Host plants play a vital role in insect population differentiation, while symbiotic associations between bacteria and insects are ubiquitous in nature. However, existing studies have given limited attention to the connection between host-related differentiation and symbiotic bacterial communities in phytophagous insects. In this study, we collected 58 samples of Aphis odinae from different host plants in southern China and constructed phylogenetic trees to investigate their differentiation in relation to host plants. We also selected aphid samples from the five most preferred host plants and analyzed their symbiotic bacterial composition using Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. The phylogeny and symbiotic bacterial community structure of A. odinae populations on different host plants showed that samples from Triadica sebifera (Euphorbiaceae) had a consistent presence of Wolbachia as the predominant secondary symbiont and suggested the possibility of undergoing differentiation. Conversely, although differentiation was observed in samples from Rhus chinensis (Anacardiaceae), no consistent presence of predominant secondary symbionts was found. Additionally, the samples from Heptapleurum heptaphyllum (Araliaceae) consistently carried Serratia, but no host differentiation was evident. In summary, this study reveals a partial correspondence between symbiotic bacterial communities and host-related differentiation in A. odinae. The findings contribute to our understanding of the microevolutionary influencing the macroevolutionary relationships between bacterial symbionts and phytophagous insects. The identification of specific symbionts associated with host-related differentiation provides valuable insights into the intricate dynamics of insect-bacteria interactions.

Innovative accumulative risk assessment of co-exposure to Cd, As, and Pb in contaminated rice based on their in vivo bioavailability and in vitro bioaccessibility.

The consumption of cadmium (Cd), arsenic (As), and lead (Pb) co-contaminated rice exposes humans to multiple heavy metals simultaneously, with relative bioavailability (RBA) and bioaccessibility (BAc) being important determinants of potential health risks. This study evaluated the relationship between in vivo RBA and in vitro BAc of Cd, As, and Pb in rice and their cumulative risk to humans. A total of 110 rice samples were collected in Zhejiang Province, China, and 10 subsamples with varying concentration gradients were randomly selected to measure RBA using a mouse model (liver, kidney, femur, blood, and urine as endpoints) and BAc using four in vitro assays (PBET, UBM, SBRC, and IVG). Our results indicated that Cd-RBA varied from 21.2 % to 67.5 %, As-RBA varied from 23.2 % to 69.3 %, and Pb-RBA varied from 22.2 % to 68.9 % based on mouse liver plus kidneys. The BAc values for Cd, As, and Pb in rice varied according to the assay. Compared to Cd and As, Pb exhibited a lower BAc in the gastric (GP) and intestinal (IP) phases. According to the relationship between the BAc and RBA values, IVG-GP (R2 = 0.92), SBRC-IP (R2 = 0.73), and UBM-GP (R2 = 0.80) could be used as predictors of Cd-, As-, and Pb-RBA in rice, respectively. The health risks associated with co-exposure to Cd, As, and Pb in contaminated rice for both adults and children exceeded the acceptable threshold, with Cd and As being the primary risk factors. The noncarcinogenic and carcinogenic risks were markedly reduced when the RBA and BAc values were incorporated into the risk assessment. Due to the risk overestimation inherent in estimating the risk level based on total metal concentration, our study provides a realistic assessment of the cumulative health risks associated with co-exposure to Cd, As, and Pb in contaminated rice using in vivo RBA and in vitro BAc bioassays.

Natural language processing with machine learning methods to analyze unstructured patient-reported outcomes derived from electronic health records: A systematic review.

OBJECTIVE: Natural language processing (NLP) combined with machine learning (ML) techniques are increasingly used to process unstructured/free-text patient-reported outcome (PRO) data available in electronic health records (EHRs). This systematic review summarizes the literature reporting NLP/ML systems/toolkits for analyzing PROs in clinical narratives of EHRs and discusses the future directions for the application of this modality in clinical care. METHODS: We searched PubMed, Scopus, and Web of Science for studies written in English between 1/1/2000 and 12/31/2020. Seventy-nine studies meeting the eligibility criteria were included. We abstracted and summarized information related to the study purpose, patient population, type/source/amount of unstructured PRO data, linguistic features, and NLP systems/toolkits for processing unstructured PROs in EHRs. RESULTS: Most of the studies used NLP/ML techniques to extract PROs from clinical narratives (n = 74) and mapped the extracted PROs into specific PRO domains for phenotyping or clustering purposes (n = 26). Some studies used NLP/ML to process PROs for predicting disease progression or onset of adverse events (n = 22) or developing/validating NLP/ML pipelines for analyzing unstructured PROs (n = 19). Studies used different linguistic features, including lexical, syntactic, semantic, and contextual features, to process unstructured PROs. Among the 25 NLP systems/toolkits we identified, 15 used rule-based NLP, 6 used hybrid NLP, and 4 used non-neural ML algorithms embedded in NLP. CONCLUSIONS: This study supports the potential utility of different NLP/ML techniques in processing unstructured PROs available in EHRs for clinical care. Though using annotation rules for NLP/ML to analyze unstructured PROs is dominant, deploying novel neural ML-based methods is warranted.

Graphidessajinfoensis, a new species of longhorned beetle (Coleoptera, Cerambycidae, Lamiinae, Desmiphorini) from China.

Graphidessajinfoensissp. nov. is described from Chongqing and Guizhou in Southwest China. The diagnostic morphological characters of the new species are described and illustrated in color plates. The distribution of all species of the genus Graphidessa Bates, 1884 is mapped and the key to all species of this genus is updated. The COI gene sequence of the new species is also provided.

Results of neonatal screening for congenital hypothyroidism and hyperphenylalaninemia in Zhejiang province from 1999 to 2022. / 浙江省1200ä¸‡ä¾‹æ–°ç”Ÿå„¿å ˆå¤©æ€§ç”²çŠ¶è ºåŠŸèƒ½å‡é€€ç—‡ã€é«˜è‹¯ä¸™æ°¨é ¸è¡€ç—‡ç­›æŸ¥ç»“æžœåˆ†æž.

OBJECTIVES: To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022. METHODS: A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry. TSH≥9 µIU/mL was considered positive for CH, while Phe>120 µmol/L and/or Phe/Tyr ratio>2.0 were considered positive for HPA. The positive newborns in screening were recalled, and the gene variations were detected by high-throughput sequencing and MassARRAY tests. RESULTS: The overall neonatal screening rate during 1999-2022 was 89.41% (11 922 318/13 333 929) and the screening rate was increased from 6.46% in 1999 to 100.0% in 2022. A total of 8924 cases of CH were diagnosed among screened newborns with an incidence rate of 1/1336. A total of 563 cases of HPA were diagnosed, including 508 cases of classic phenylketonuria (cPKU) and 55 cases of tetrahydrobiopterin deficiency (BH4D), with an incidence rate of 1/21 176. Ninety-seven out of 8924 cases of CH underwent genetic analysis. Gene mutations were detected in 9 CH related genes, the highest frequency mutations were found in DUOX2 gene (69.0%) with c.3329G>A (p.R1110Q) (18.2%) and c.1588A>T (p.K530X) (17.3%) as the hotspot mutations. There were 81 PAH gene variants detected in a total of 250 cases of cPKU, and c728G>A (p.R243Q) (24.4%), c.721C>T (p.R241C) (15.0%) were the hotspot mutations. Meanwhile 7 novel variants in PAH gene were detected: c.107C>A (p.S36*), c.137G>T (p.G46V), c.148A>G(p.K50E), c.285C>T (p.I95I), c.843-10delTTCC, exon4-7del and c.1066-2A>G. There were 12 PTS gene variants detected in 36 cases of BH4D, and c.259C>T (p.P87S) (31.9%) was the hotspot mutation. CONCLUSIONS: The incident of CH has increased from 1999 to 2022 in Zhejiang province, and it is higher than that of national and global levels; while the incidence of HPA is similar to the national average. DUOX2 gene variation is the most common in CH patients; c.728G>A (p.R243Q) is the hotspot mutation in cPKU patients, while c.259C>T (p.P87S) is the hotspot mutation in BH4D patients.

Digital Personal Health Coaching Platform for Promoting Human Papillomavirus Infection Vaccinations and Cancer Prevention: Knowledge Graph-Based Recommendation System.

BACKGROUND: Health promotion can empower populations to gain more control over their well-being by using digital interventions that focus on preventing the root causes of diseases. Digital platforms for personalized health coaching can improve health literacy and information-seeking behavior, leading to better health outcomes. Personal health records have been designed to enhance patients' self-management of a disease or condition. Existing personal health records have been mostly designed and deployed as a supplementary service that acts as views into electronic health records. OBJECTIVE: We aim to overcome some of the limitations of electronic health records. This study aims to design and develop a personal health library (PHL) that generates personalized recommendations for human papillomavirus (HPV) vaccine promotion and cancer prevention. METHODS: We have designed a proof-of-concept prototype of the Digital Personal Health Librarian, which leverages machine learning; natural language processing; and several innovative technological infrastructures, including the Semantic Web, social linked data, web application programming interfaces, and hypermedia-based discovery, to generate a personal health knowledge graph. RESULTS: We have designed and implemented a proof-of-the-concept prototype to showcase and demonstrate how the PHL can be used to store an individual's health data, for example, a personal health knowledge graph. This is integrated with web-scale knowledge to support HPV vaccine promotion and prevent HPV-associated cancers among adolescents and their caregivers. We also demonstrated how the Digital Personal Health Librarian uses the PHL to provide evidence-based insights and knowledge-driven explanations that are personalized and inform health decision-making. CONCLUSIONS: Digital platforms such as the PHL can be instrumental in improving precision health promotion and education strategies that address population-specific needs (ie, health literacy, digital competency, and language barriers) and empower individuals by facilitating knowledge acquisition to make healthy choices.

Corrosion-resistant cobalt phosphide electrocatalysts for salinity tolerance hydrogen evolution.

Seawater electrolysis is a viable method for producing hydrogen on a large scale and low-cost. However, the catalyst activity during the seawater splitting process will dramatically degrade as salt concentrations increasing. Herein, CoP is discovered that could reject chloride ions far from catalyst in electrolyte based on molecular dynamic simulation. Thus, a binder-free electrode is designed and constructed by in-situ growth of homogeneous CoP on rGO nanosheets wrapped around the surface of Ti fiber felt for seawater splitting. As expected, the as-obtained CoP/rGO@Ti electrode exhibits good catalytic activity and stability in alkaline electrolyte. Especially, benefitting from the highly effective repulsive Cl- intrinsic characteristic of CoP, the catalyst maintains good catalytic performance with saturated salt concentration, and the overpotential increasing is less than 28 mV at 10 mA cm-2 from 0 M to saturated NaCl in electrolyte. Furthermore, the catalyst for seawater splitting performs superior corrosion-resistance with a low solubility of 0.04%. This work sheds fresh light into the development of efficient HER catalysts for salinity tolerance hydrogen evolution.

Two new species of Aphis (Toxoptera) Koch (Hemiptera, Aphididae) from China.

Two new aphid species, Aphis (Toxoptera) fafuensis Cheng & Huang, sp. nov., feeding on Adinandramillettii (Pentaphylacaceae) from Fujian, China, and Aphis (Toxoptera) sennae Cheng & Huang, sp. nov., feeding on Sennabicapsularis (Fabaceae) from Yunnan, China, were described. Morphological characters and molecular data supported the taxonomic position of the new species within the subgenus Aphis (Toxoptera). A key for identifying species of apterous viviparous females in this subgenus is provided.

Skeleton-CutMix: Mixing Up Skeleton With Probabilistic Bone Exchange for Supervised Domain Adaptation.

We present Skeleton-CutMix, a simple and effective skeleton augmentation framework for supervised domain adaptation and show its advantage in skeleton-based action recognition tasks. Existing approaches usually perform domain adaptation for action recognition with elaborate loss functions that aim to achieve domain alignment. However, they fail to capture the intrinsic characteristics of skeleton representation. Benefiting from the well-defined correspondence between bones of a pair of skeletons, we instead mitigate domain shift by fabricating skeleton data in a mixed domain, which mixes up bones from the source domain and the target domain. The fabricated skeletons in the mixed domain can be used to augment training data and train a more general and robust model for action recognition. Specifically, we hallucinate new skeletons by using pairs of skeletons from the source and target domains; a new skeleton is generated by exchanging some bones from the skeleton in the source domain with corresponding bones from the skeleton in the target domain, which resembles a cut-and-mix operation. When exchanging bones from different domains, we introduce a class-specific bone sampling strategy so that bones that are more important for an action class are exchanged with higher probability when generating augmentation samples for that class. We show experimentally that the simple bone exchange strategy for augmentation is efficient and effective and that distinctive motion features are preserved while mixing both action and style across domains. We validate our method in cross-dataset and cross-age settings on NTU-60 and ETRI-Activity3D datasets with an average gain of over 3% in terms of action recognition accuracy, and demonstrate its superior performance over previous domain adaptation approaches as well as other skeleton augmentation strategies.

Potential Global Invasion Risk of Scale Insect Pests Based on a Self-Organizing Map.

In the present study, a global presence/absence dataset including 2486 scale insect species in 157 countries was extracted to assess the establishment risk of potential invasive species based on a self-organizing map (SOM). According to the similarities in species assemblages, a risk list of scale insects for each country was generated. Meanwhile, all countries in the dataset were divided into five clusters, each of which has high similarities of species assemblages. For those countries in the same neuron of the SOM output, they may pose the greatest threats to each other as the sources of potential invasive scale insect species, and therefore, require more attention from quarantine departments. In addition, normalized ζi values were used to measure the uncertainty of the SOM output. In total, 9 out of 63 neurons obtained high uncertainty with very low species counts, indicating that more investigation of scale insects should be undertaken in some parts of Africa, Asia and Northern Europe.