Utilization of traditional Chinese medicine in the management of cutaneous ulceration induced by cervical lymph node metastasis in tonsillar carcinoma: A case report.

OBJECTIVE: Cutaneous ulcers induced by metastasis present a challenging clinical issue, often resistant to conventional dressing change interventions. In this case, we demonstrates the efficacy of Traditional Chinese Medicine in managing ruptured tumors. CASE PRESENTATION: We present a case study of a 40-year-old Chinese male patient diagnosed with advanced tonsillar squamous cell carcinoma with cervical lymph node metastasis and cutaneous ulceration. Despite nearly six months of conventional dressing treatment yielding minimal improvement, significant healing of the ulcerated surface of the neck metastasis was observed after approximately two months of decoction therapy. The cancerous lesion exhibited a reduction of nearly 90 %, with concomitant alleviation of secondly symptoms such as cold intolerance, excessive sweating, anxiety and depression. CONCLUSIONS: In this case, we introduces Traditional Chinese Medicine may be an effective alternative therapy for the treatment of cancer-related disease. And it may also be an optional therapeutic approach for healthcare practitioners with cutaneous carcinoma ulceration.

Ginkgo biloba extract safety: Insights from a real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events.

ETHNOPHARMACOLOGICAL RELEVANCE: A traditional Chinese medicine extracted from the Ginkgophyta, Ginkgo biloba is commonly used to treat cardiac cerebral disease all over the world. Limited data exist regarding adverse drug reactions associated with Ginkgo biloba extract post-marketing. AIM OF THE STUDY: Currently, the drug safety profile of Ginkgo biloba extract is assessed using a substantial volume of case safety reports within the FDA Adverse Event Reporting System (FAERS) database. MATERIALS AND METHODS: The study collected adverse events (AEs) data associated with Ginkgo biloba extract as the primary suspected drug from 2004 to 2023 from the FAERS database. A standardized mapping analysis of System Organ Class (SOC) and preferred term (PT) was conducted. Utilizing reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayes geometric mean (EBGM), significant disproportionate measurement signals of adverse drug reactions (ADR) were identified and high-intensity signals were analyzed. RESULTS: 700 reports of adverse events related to Ginkgo biloba extract were found in the FAERS database, affecting 23 organ systems. 88 significant mismatches were identified using four algorithms, leading to unexpected major adverse events like amaurosis fugax, fractional exhaled nitric oxide created, and obstructive sleep apnoea syndrome. The study observed a median onset time of AE associated with Ginkgo biloba extract at 7 days (interquartile interval [IQR] 0-109 days), with the majority of AE manifesting within the initial 7 days of drug treatment initiation. This investigation identified a noteworthy AE signal for Ginkgo biloba extract, underscoring the importance of clinical surveillance and risk assessment in its use. CONCLUSIONS: In clinical practice, this study provides a deeper and broader understanding of suspected adverse reactions associated with Ginkgo biloba extract.

Current status and influencing factors of protective motivation for body mass management during pregnancy.

OBJECTIVE: Excessive weight gain, obesity, or insufficient weight gain during pregnancy can adversely affect both the mother and her offspring. This study aims to investigate the relationship between pregnant women's self-perception and beliefs and their body weight management during pregnancy. METHODS: A cross-sectional survey involving 350 pregnant women in Changsha City was conducted from July to September 2023. Instruments included a sociodemographic data sheet, protective motivation questionnaire for pregnancy body quality management, and scales measuring body image, anxiety, self-efficacy, and social support. Univariate analysis and multiple linear regression were employed to identify factors influencing protective motivation for body quality management during pregnancy. RESULTS: The average score of the protective motivation questionnaire was 124 (SD = 13.07), suggesting a need for enhanced weight management. Key factors influencing protective motivation included household income, cooperation with healthcare workers, sources of pregnancy information, midnight snacking habits, prepregnancy exercise, body image, and self-efficacy (P < 0.05). CONCLUSION: The study highlights significant factors influencing pregnant women's motivation for body quality management. These include economic status, healthcare collaboration, information accessibility, lifestyle habits, and psychological factors. The findings underscore the need for healthcare professionals to integrate these factors into pregnancy care programs to improve body quality management.

Direct detection of endogenous Gαi activity in cells with a sensitive conformational biosensor.

Activation of heterotrimeric G-proteins (Gαßγ) by G-protein-coupled receptors (GPCRs) is not only a mechanism broadly used by eukaryotes to transduce signals across the plasma membrane, but also the target for a large fraction of clinical drugs. However, approaches typically used to assess this signaling mechanism by directly measuring G-protein activity, like optical biosensors, suffer from limitations. On one hand, many of these biosensors require expression of exogenous GPCRs and/or G-proteins, compromising readout fidelity. On the other hand, biosensors that measure endogenous signaling may still interfere with the signaling process under investigation or suffer from having a small dynamic range of detection, hindering broad applicability. Here, we developed an optical biosensor that detects the endogenous G-protein active species Gαi-GTP upon stimulation of endogenous GPCRs more robustly than current state-of-the-art sensors for the same purpose. Its design is based on the principle of bystander Bioluminescence Resonance Energy Transfer (BRET) and leverages the Gαi-binding protein named GINIP as a high affinity and specific detector module of the GTP-bound conformation of Gαi. We optimized this design to prevent interference with Gi-dependent signaling (cAMP inhibition) and to enable implementation in different experimental systems with endogenous GPCRs, including neurotransmitter receptors in primary astroglial cells or opioid receptors in cell lines, which revealed opioid neuropeptide-mediated activation profiles different from those observed with other biosensors involving exogenous GPCRs and G-proteins. Overall, we introduce a biosensor that directly and sensitively detects endogenous activation of G-proteins by GPCRs across different experimental settings without interfering with the subsequent propagation of signaling.

Nutritional status and neurodevelopmental levels in infants at high risk of cerebral palsy.

Importance: Nutrition is associated with neurodevelopment. Infants at high risk of cerebral palsy (CP) usually suffer from undernutrition, yet the relationship between nutritional status and neurodevelopmental levels is unclear. Objective: To describe the nutritional status characteristics of infants at high risk of CP, and to explore the relationship between neurodevelopmental levels and nutritional status. Methods: This single-center cross-sectional study enrolled infants at high risk of CP, with corrected age from 0 days to 12 months. Weight and height were measured and calculated into z-scores, which were used to classify the nutritional status based on the World Health Organization growth charts and American Society for Parenteral and Enteral Nutrition standards. The Bayley Scales of Infant and Toddler Development were used to evaluate the developmental levels of gross motor, fine motor, cognition, receptive communication, and expressive communication. Results: A total of 479 infants at high risk of CP were recruited, with 43.4% classified as undernutrition. Compared to those with normal neurodevelopment, the odds of moderate and severe undernutrition were about 1.8 and 3.9 times higher in gross motor delay, 2.2 and 3.1 times higher in fine motor delay, 2.5 and 9.4 times higher in cognition delay, 2.2 and 3.9 times higher in receptive communication delay, and 3.0 and 5.6 times higher in expressive communication delay. There were significant positive correlations between nutritional status and neurodevelopmental levels (P < 0.001). Interpretation: Undernutrition and neurodevelopmental delays are prevalent among infants at high risk of CP. Worse nutritional status was correlated with lower neurodevelopmental levels.

Recent advances in sialic acid-based active targeting chemoimmunotherapy promoting tumor shedding: a systematic review.

Tumors have always been a major public health concern worldwide, and attempts to look for effective treatments have never ceased. Sialic acid is known to be a crucial element for tumor development and its receptors are highly expressed on tumor-associated immune cells, which perform significant roles in establishing the immunosuppressive tumor microenvironment and further boosting tumorigenesis, progression, and metastasis. Obviously, it is essential to consider sophisticated crosstalk between tumors, the immune system, and preparations, and understand the links between pharmaceutics and immunology. Sialic acid-based chemoimmunotherapy enables active targeting drug delivery via mediating the recognition between the sialic acid-modified nano-drug delivery system represented by liposomes and sialic acid-binding receptors on tumor-associated immune cells, which inhibit their activity and utilize their homing ability to deliver drugs. Such a "Trojan horse" strategy has remarkably improved the shortcomings of traditional passive targeting treatments, unexpectedly promoted tumor shedding, and persistently induced robust immunological memory, thus highlighting its prospective application potential for targeting various tumors. Herein, we review recent advances in sialic acid-based active targeting chemoimmunotherapy to promote tumor shedding, summarize the current viewpoints on the tumor shedding mechanism, especially the formation of durable immunological memory, and analyze the challenges and opportunities of this attractive approach.

Turn-on mode probe based on the sustainable xanthohumol extract for the efficient viscosity response in a liquid system.

Viscosity is a typical physical parameter and plays an important role in nutrient transferring, diffusion process regulating and safety warning. Aberrant mitochondrial viscosity is closely associated with an imbalance in a liquid system. Nevertheless, there is currently a lack of convenient and efficient tools for the mutation of viscosity detection at the molecular level. Herein, a natural product xanthohumol (XTH) was extracted from Humulus lupulus and used to measure the microenvironmental viscosity. Due to the existence of carbonyl and phenolic hydroxyl groups, a typical twisted intramolecular charge transfer (TICT) was formed. The conjugated single and double bonds can be employed as the rotatable site. Consequently, a turn-on method based on viscosity response is developed. High sensitivity (x = 0.56) with a remarkable enhancement (55-fold) toward viscosity and a visualized fluorescent signal can be found. In addition, it displays a single selectivity with excellent photostability and pH stability in the complex liquid system. Using the extracted XTH, a typical application toward the liquid spoilage process was performed and a positive correlation was noted. Given the comprehensive properties of XTH, liquid safety inspection at a molecular level with natural source-extracted products can be obtained.

The biosynthesis of asiaticoside and madecassoside reveals tandem duplication-directed evolution of glycoside glycosyltransferases in the Apiales.

Certain plant species within the Apiales order accumulate triterpenoid saponins that feature a distinctive glucose-glucose-rhamnose (G-G-R) sugar chain attached at the C-28 position of the pentacyclic triterpene skeleton. Until recently, the genomic basis underlying the biosynthesis and evolution of this sugar chain has remained elusive. In this study, we identified two novel glycoside glycosyltransferases (GGTs) that can sequentially install the sugar chain's second D-glucose and third L-rhamnose during the biosynthesis of asiaticoside and madecassoside, two representative G-G-R sugar chain-containing triterpenoid saponins produced by Centella asiatica. Enzymatic assays revealed the remarkable substrate promiscuity of the two GGTs and the key residues crucial for sugar-donor selectivity of the glucosyltransferase and rhamnosyltransferase. We further identified syntenic tandem gene duplicates of the two GGTs in the Apiaceae and Araliaceae families, suggesting a well-conserved genomic basis underlying sugar chain assembly that likely has evolved in the early ancestors of the Apiales order. Moreover, expression patterns of the two GGTs in pierced leaves of C. asiatica were found to be correlated with the production of asiaticoside and madecassoside, implying their involvement in host defense against herbivores and pathogens. Our work sheds light on the biosynthesis and evolution of complex saponin sugars, paving the way for future engineering of diverse bioactive triterpenoids with unique glycoforms.

Clinical Effect Analysis of Fire-needle Acupuncture at Neiyingxiang Treating Persistent Allergic Rhinitis.

OBJECTIVES: We conducted the first trial to evaluate the effect that fire-needle acupuncture at Neiyingxiang (ExHN 9) in patients with moderate to severe persistent AR. METHODS: This was a randomized, single-center, sham, and placebo-controlled rial. Patients were kept blinded to their group assignment. All participants were equally assigned to the fire-needle acupuncture (FA) treatment group, sham fire-needle acupuncture (SFA) group, or loratadine group. The trial was designed with an acupuncture intervention once a week for 4 weeks and follow-up 4 weeks. The Total Nasal Symptom Scores (TNSS), Total Non-Nasal Symptom Scores (TNNSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Allergic Rhinitis Control Test (ARCT), and total nasal resistance of 150 Pa were evaluated as outcome measures. RESULTS: A total of 180 participants were enrolled, and 175 participants completed the trials. At 2 and 4 weeks, the TNSS, TNNSS, and RQLQ scores of the FA and loratadine groups were significantly lower than those of the SFA group. At 8 weeks, the scores of loratadine group increased compared with the FA group (Cohen's d >0.80, p < 0.01). The ACRT score of the FA treatment group rose gradually. After treatment, the total nasal resistance of the FA group was significantly decreased and was lower than that of the other two groups (Cohen's d >0.80, p < 0.01). CONCLUSION: Fire-needle acupuncture at Neiyingxiang (ExHN 9) is effective for improving nasal allergy symptoms and quality of life in patients with moderate and severe persistent AR, and the duration of its effects is long. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:4471-4479, 2024.

Novel coumarin-based ratiometric bifunctional fluorescent probe mimicking a set-reset memorized device.

A novel coumarin-based fluorescent sensor CHE, incorporating 2-hydrazinylbenzothiazole and coumarin aldehyde, has been developed that demonstrated a preferential detection of Hg2+ and Ag+ in presence of interferences. Compared to previously prevalent intensity-based fluorescent probes, CHE exhibited a ratiometric fluorescence response to Hg2+ and Ag+, and further accurately differentiated Hg2+ and Ag + using the differential extractive ability of EDTA when interacting with ion-CHE complexes. Sensing mechanism was investigated and elucidated. The chemosensor CHE was successfully applied to detect Hg2+ and Ag+ in six distinct samples with satisfactory results. Additionally, combinatorial logic circuits were constructed utilizing three distinct logic gates (NOT, OR, and INH) based on the sensor's differential output signals in response to Hg2+/Ag+ and other cations. Interestingly, utilizing the reversible and reproducible switching behavior of the EDTA interaction with Hg2+, a conceptual 'Write-Read-Erase-Read' memory function with multi-write capability was proposed, offering a novel perspective for molecular-based memory systems.

The Relationship and Effects of Self-Esteem and Body Shape on Eating Disorder Behavior: A Cross-Sectional Survey of Chinese University Students.

BACKGROUND: Eating disorders (EDs) have become a global public health concern among adolescents and young adults. However, Chinese university students exhibit a high prevalence of eating disorders. This study aims to investigate the effects of self-esteem (SE) and body shape (BS) on ED behaviors among Chinese university students. METHODS: Using random sampling, 946 Chinese university students (aged 18 to 24, M = 19.94, SD = 1.04) participated in a survey comprising the Sick, Control, One, Fat, and Food Questionnaire (SCOFF-Q), the Body Shape Questionnaire (BS-Q), and the Rosenberg Self-Esteem Scale (RS-S) to assess their eating disorder or non-eating disorder (NED) behavior. RESULTS: There was a significant positive correlation between body shape and eating disorder behaviors (r = 0.19, p < 0.01), while there was a significant negative correlation between self-esteem and eating disorder behaviors (r = -0.14, p = 0.001 < 0.01). Gender was a moderating factor in the relationship between body shape and eating disorder behaviors (t = 3.14, p = 0.002 < 0.01), while parents' marital status was a moderating factor in the relationship between self-esteem and eating disorder behavior (t = 2.72, p = 0.007 < 0.01). Body shape (z = 6.47, p = 0.001 < 0.01), self-esteem (z = -2.81, p = 0.005 < 0.05), and gender (z = 3.06, p = 0.002 < 0.01) significantly influenced eating disorder behavior among Chinese university students aged 18-24 years. CONCLUSIONS: There was a direct effect between body shape and self-esteem and eating disorder behaviors among Chinese university students aged 18-24 years. Alarmingly, female university students are becoming susceptible to external influences on self-esteem and body shape, leading to eating disorder behaviors at an increasingly younger age in China.

Endoplasmic reticulum stress: bridging inflammation and obesity-associated adipose tissue.

Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within the context of obesity, lipid metabolism, adipose tissue formation, and inflammation are intricately linked to endoplasmic reticulum stress (ERS). ERS modulates metabolism, insulin signaling, inflammation, as well as cell proliferation and death through the unfolded protein response (UPR) pathway. Serving as a crucial nexus, ERS bridges the functionality of adipose tissue and the inflammatory response. In this review, we comprehensively elucidate the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, aiming to offer insights into targeting ERS for ameliorating metabolic dysregulation in obesity-associated chronic diseases such as hyperlipidemia, hypertension, fatty liver, and type 2 diabetes.

High-fat diet consumption promotes adolescent neurobehavioral abnormalities and hippocampal structural alterations via microglial overactivation accompanied by an elevated serum free fatty acid concentration.

Mounting evidence suggests that high-fat diet (HFD) consumption increases the risk for depression, but the neurophysiological mechanisms involved remain to be elucidated. Here, we demonstrated that HFD feeding of C57BL/6J mice during the adolescent period (from 4 to 8 weeks of age) resulted in increased depression- and anxiety-like behaviors concurrent with changes in neuronal and myelin structure in the hippocampus. Additionally, we showed that hippocampal microglia in HFD-fed mice assumed a hyperactive state concomitant with increased PSD95-positive and myelin basic protein (MBP)-positive inclusions, implicating microglia in hippocampal structural alterations induced by HFD consumption. Along with increased levels of serum free fatty acids (FFAs), abnormal deposition of lipid droplets and increased levels of HIF-1α protein (a transcription factor that has been reported to facilitate cellular lipid accumulation) within hippocampal microglia were observed in HFD-fed mice. The use of minocycline, a pharmacological suppressor of microglial overactivation, effectively attenuated neurobehavioral abnormalities and hippocampal structural alterations but barely altered lipid droplet accumulation in the hippocampal microglia of HFD-fed mice. Coadministration of triacsin C abolished the increases in lipid droplet formation, phagocytic activity, and ROS levels in primary microglia treated with serum from HFD-fed mice. In conclusion, our studies demonstrate that the adverse influence of early-life HFD consumption on behavior and hippocampal structure is attributed at least in part to microglial overactivation that is accompanied by an elevated serum FFA concentration and microglial aberrations represent a potential preventive and therapeutic target for HFD-related emotional disorders.

Evaluation of Rhododendri Mollis Flos and its representative component as a potential analgesic.

Rhododendri Mollis Flos (R. mole Flos), the dried flowers of Rhododendron mole G. Don, have the ability to relieve pain, dispel wind and dampness, and dissolve blood stasis, but they are highly poisonous. The significance of this study is to explore the analgesic application potential of R. mole Flos and its representative component. According to the selected processing methods recorded in ancient literature, the analgesic activities of wine- and vinegar-processed R. mole Flos, as well as the raw product, were evaluated in a writhing test with acetic acid and a formalin-induced pain test. Subsequently, the HPLC-TOP-MS technique was utilized to investigate the changes in active components before and after processing once the variations in activities were confirmed. Based on the results, rhodojaponin VI (RJ-Vl) was chosen for further study. After processing, especially in vinegar, R. mole Flos did not only maintain the anti-nociception but also showed reduced toxicity, and the chemical composition corresponding to these effects also changed significantly. Further investigation of its representative components revealed that RJ-VI has considerable anti-nociceptive activity, particularly in inflammatory pain (0.3 mg/kg) and peripheral neuropathic pain (0.6 mg/kg). Its toxicity was about three times lower than that of rhodojaponin III, which is another representative component of R. mole Flos. Additionally, RJ-VI mildly inhibits several subtypes of voltage-gated sodium channels (IC50 > 200 µM) that are associated with pain or cardiotoxicity. In conclusion, the chemical substances and biological effects of R. mole Flos changed significantly before and after processing, and the representative component RJ-VI has the potential to be developed into an effective analgesic.

A derivative of trihydroxynaphthalenone and a pyrone metabolite from the endophytic fungus Talaromyces purpurpgenus.

A newly discovered trihydroxynaphthalenone derivative, epoxynaphthalenone (1) involving the condensation of ortho-hydroxyl groups into an epoxy structure, and a novel pyrone metabolite characterized as pyroneaceacid (2), were extracted from Talaromyces purpurpgenus, an endophytic fungus residing in Rhododendron molle. The structures of these compounds were elucidated through a comprehensive analysis of their NMR and HRESIMS data. The determination of absolute configurations was accomplished using electronic circular dichroism (ECD) calculations and CD spectra. Notably, these recently identified metabolites exhibited a moderate inhibitory activity against xanthine oxidase (XOD).

Quercetin Limits Tumor Immune Escape through PDK1/CD47 Axis in Melanoma.

Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.

Functional Characterization of the Niemann-Pick C2 Protein BdioNPC2b in the Parasitic Wasp Baryscapus dioryctriae (Chalcidodea: Eulophidae).

Reverse chemical ecology has been widely applied for the functional characterization of olfactory proteins in various arthropods, but few related studies have focused on parasitic wasps. Here, the odorant carrier Niemann-Pick C2 protein of Baryscapus dioryctriae (BdioNPC2b) was studied in vitro and in vivo. Ligand binding analysis revealed that BdioNPC2b most strongly bound to 2-butyl-2-octenal and which compound could elicit an EAG response and attracted B. dioryctriae adults. Moreover, this odorant attractant significantly improved the reproductive efficiency of B. dioryctriae compared to that of the control. Then, the relationship between BdioNPC2b and 2-butyl-2-octenal was validated by RNAi, and site-directed mutagenesis revealed the involvement of three key residues of BdioNPC2b in binding to 2-butyl-2-octenal through hydrogen bonding. Our findings provide not only a deeper understanding of the olfactory function of NPC2 in wasps but also useful information for improving the performance of the parasitoid B. dioryctriae as a biological control agent.

Aboveground Biomass Mapping and Analysis of Spatial Drivers in the Qinghai-Xizang Plateau Permafrost Zone: A Case Study of the Beilu River Basin.

Aboveground biomass (AGB) serves as a crucial measure of ecosystem productivity and carbon storage in alpine grasslands, playing a pivotal role in understanding the dynamics of the carbon cycle and the impacts of climate change on the Qinghai-Xizang Plateau. This study utilized Google Earth Engine to amalgamate Landsat 8 and Sentinel-2 satellite imagery and applied the Random Forest algorithm to estimate the spatial distribution of AGB in the alpine grasslands of the Beiliu River Basin in the Qinghai-Xizang Plateau permafrost zone during the 2022 growing season. Additionally, the geodetector technique was employed to identify the primary drivers of AGB distribution. The results indicated that the random forest model, which incorporated the normalized vegetation index (NDVI), the enhanced vegetation index (EVI), the soil-adjusted vegetation index (SAVI), and the normalized burn ratio index (NBR2), demonstrated robust performance in regards to AGB estimation, achieving an average coefficient of determination (R2) of 0.76 and a root mean square error (RMSE) of 70 g/m2. The average AGB for alpine meadows was determined to be 285 g/m2, while for alpine steppes, it was 204 g/m2, both surpassing the regional averages in the Qinghai-Xizang Plateau. The spatial pattern of AGB was primarily driven by grassland type and soil moisture, with q-values of 0.63 and 0.52, and the active layer thickness (ALT) also played a important role in AGB change, with a q-value of 0.38, demonstrating that the influences of ALT should not be neglected in regards to grassland change.

Proteomic changes of botulinum neurotoxin injection on muscle growth in children with spastic cerebral palsy.

PURPOSE: The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP). EXPERIMENTAL DESIGN: A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting. RESULTS: Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways. CONCLUSION AND CLINICAL RELEVANCE: BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.

Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.

G protein-coupled receptors (GPCRs) are the largest family of druggable proteins encoded in the human genome, but progress in understanding and targeting them is hindered by the lack of tools to reliably measure their nuanced behavior in physiologically relevant contexts. Here, we developed a collection of compact ONE vector G-protein Optical (ONE-GO) biosensor constructs as a scalable platform that can be conveniently deployed to measure G-protein activation by virtually any GPCR with high fidelity even when expressed endogenously in primary cells. By characterizing dozens of GPCRs across many cell types like primary cardiovascular cells or neurons, we revealed insights into the molecular basis for G-protein coupling selectivity of GPCRs, pharmacogenomic profiles of anti-psychotics on naturally occurring GPCR variants, and G-protein subtype signaling bias by endogenous GPCRs depending on cell type or upon inducing disease-like states. In summary, this open-source platform makes the direct interrogation of context-dependent GPCR activity broadly accessible.