Enhancing UHPC Tensile Performance Using Polystyrene Beads: Significant Improvements and Mechanisms.

This study investigates utilizing spherical polystyrene (PS) beads as artificial flaws to improve ultrahigh-performance concrete (UHPC) tensile performance using a uniaxial tensile test and explains the corresponding mechanisms by analyzing the internal material structure of UHPC specimens with X-ray CT scanning. With a hooked steel fiber volume fraction of 2%, three PS bead dosages were employed to study tensile behavior changes in dog-bone UHPC specimens. A 33.4% increase in ultimate tensile strength and 174.8% increase in ultimate tensile strain were recorded after adding PS beads with a volume fraction of 2%. To explain this improvement, X-ray CT scanning was utilized to investigate the post-test internal material structures of the dog-bone specimens. AVIZO software was used to analyze the CT information. The CT results revealed that PS beads could not only serve as the artificial flaws to increase the cracking behavior of the matrix of UHPC but also significantly optimize the fiber orientation. The PS beads could serve as stirrers during the mixing process to distribute fiber more uniformly. The test results indicate a relationship between fiber orientation and UHPC tensile strength.

A Dual-Polarization Programmable Metasurface for Green and Secure Wireless Communication.

Dual-polarization programmable metasurfaces can flexibly manipulate electromagnetic (EM) waves while providing approximately twice the information capacity. Therefore, they hold significant applications in next-generation communication systems. However, there are three challenges associated with the existing dual-polarization programmable metasurfaces. This article aims to propose a novel design to address them. First, the design overcomes the challenge of element- and polarization-independent controls, enabling more powerful manipulations of EM waves. Second, by using more energy-efficient tunable components and reducing their number, the design can be nearly passive (maximum power consumption of 27.7 mW), leading to a significant decrease in the cost and power consumption of the system (at least two orders of magnitude lower than the power consumption of conventional programmable metasurfaces). Third, the design can operate in a broad bandwidth, which is attractive for practical engineering applications. Both the element and array of the metasurface are meticulously designed, and their performance has been carefully studied. The experiments demonstrate that 2D wide-angle beam scanning can be realized. Moreover, secure communication based on directional information modulation can be implemented by exploiting the metasurface and an efficient discrete optimization algorithm, showing its programmable, multiplexing, broadband, green, and secure features.

LncRNA DYNLRB2-AS1 promotes gemcitabine resistance of nasopharyngeal carcinoma by inhibiting the ubiquitination degradation of DHX9 protein.

Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15 % of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.

PJA1-mediated suppression of pyroptosis as a driver of docetaxel resistance in nasopharyngeal carcinoma.

Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.

Corrigendum: Ultrasound-based radiomics analysis for differentiating benign and malignant breast lesions: from static images to CEUS video analysis.

[This corrects the article DOI: 10.3389/fonc.2022.951973.].

Transvaginal versus transabdominal specimen extraction in minimally invasive surgery: a systematic review and meta-analysis.

AIM: Natural orifice specimen extraction (NOSE) is an alternative to conventional transabdominal retrieval. We aimed to compare outcomes following transvaginal specimen extraction (TVSE) and transabdominal specimen extraction (TASE) in minimally invasive abdominal surgery. METHODS: An electronic database search of PubMed, Embase and CENTRAL was performed from inception until March 2023. Comparative studies evaluating TVSE versus TASE in adult female patients were included. Studies involving transanal NOSE, endoluminal surgery, or TVSE with concomitant hysterectomy were excluded. Weighted mean differences (WMD) and odds ratio were estimated for continuous and dichotomous outcomes respectively. Primary outcomes were postoperative day 1 (POD1) pain and length of stay (LOS). Secondary outcomes were operative time, rescue analgesia, morbidity, and cosmesis. A review of sexual, oncological, and technical outcomes was performed. RESULTS: Thirteen studies (2 randomised trials, 11 retrospective cohort studies), involving 1094 patients (TASE 583, TVSE 511), were included in the analysis. Seven studies involved colorectal disease and six assessed gynaecological conditions. TVSE resulted in significantly decreased POD1 pain (WMD 1.08, 95% CI: 0.49, 1.68) and shorter LOS (WMD 1.18 days, 95% CI: 0.14, 2.22), compared to TASE. Operative time was similar between both groups, with fewer patients requiring postoperative rescue analgesia with TVSE. Overall morbidity rates, as well as both wound-related and non-wound related complication rates were better with TVSE, while anastomotic morbidity rates were comparable. Cosmetic scores were higher with TVSE. TVSE did not result in worse sexual or oncological outcomes. CONCLUSION: TVSE may be feasible and beneficial compared to TASE when performed by proficient laparoscopic operators, using appropriate selection criteria. Continued evaluation with prospective studies is warranted.

T cell-redirecting antibody for treatment of solid tumors via targeting mesothelin.

T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC50: 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence of non-membrane-anchored MSLN (soluble MSLN). Moreover, the anti-tumor activity of MSLN490 was enhanced when combined with either Atezolizumab or TAA × CD28 BsAbs. Notably, a synergistic effect was observed between MSLN490 and paclitaxel, as paclitaxel disrupted the immunosuppressive microenvironment within solid tumors, enhancing immune cells infiltration and improved anti-tumor efficacy. Overall, MSLN490 exhibits robust anti-tumor activity, resilience to soluble MSLN interference, and enhanced anti-tumor effects when combined with other therapies, offering a promising future for the treatment of a variety of solid tumors. This study provides a strong foundation for further exploration of MSLN490's clinical potential.

Postoperative outcomes after prehabilitation for colorectal cancer patients undergoing surgery: a systematic review and meta-analysis of randomized and nonrandomized studies.

PURPOSE: Prehabilitation (PH) is purported to improve patients' preoperative functional status. This systematic review and meta-analysis sought to compare short-term postoperative outcomes between patients who underwent a protocolized PH program and the existing standard of care among colorectal cancer patients awaiting surgery. METHODS: A search in MEDLINE/PubMed, the Cochrane Library, Embase, Scopus, and CINAHL was conducted to identify relevant articles. Repetitive and exhaustive combinations of MeSH search terms ("prehabilitation," "colorectal cancer," "colon cancer," and "rectal cancer") were used to identify randomized and nonrandomized studies comparing PH versus standard of care for colorectal cancer patients awaiting surgery. The primary outcomes included postoperative morbidity, length of hospital stay, and readmission rates. RESULTS: Seven studies including 1,042 colorectal cancer patients (PH, 382) were included. No significant differences were found in intraoperative outcomes. The postoperative complication rates were comparable between groups (Clavien-Dindo grades I and II: risk ratio, 0.82; 95% confidence interval, 0.62-1.07; P=0.15; Clavien-Dindo grades ≥III: risk ratio, 1.02; 95% confidence interval, 0.72-1.44; P=0.92). There were also no significant differences in length of hospital stay (P=0.21) or the risk of 30-day readmission (P=0.68). CONCLUSION: Although PH does not appear to improve short-term postoperative outcomes following colorectal cancer surgery, the quality of evidence is impaired by the limited trials and heterogeneity. Thus, further large-scale trials are warranted to draw definitive conclusions and establish the long-term effects of PH.

The Future-oriented Repetitive Thought (FoRT) scale: Validation in Chinese samples and application in the schizophrenia spectrum.

BACKGROUND: Repetitive thoughts are usually associated with psychopathology. The Future-oriented Repetitive Thought (FoRT) Scale is a measure designed to capture frequency of repetitive thought about positive and negative future events. However, the validity of the scale in Chinese population and its application in the schizophrenia spectrum have not been examined. METHODS: The current study aimed to examine the psychometric properties of the Chinese version of the FoRT scale and to apply it to the schizophrenia spectrum. In Study 1, three samples (total N = 1875) of university students were recruited for exploratory factor analysis, confirmatory factor analysis, and validity test, respectively. In Study 2, we identified subsamples with high schizotypal traits (N = 89) and low schizotypal traits (N = 89), and recruited 36 inpatients with schizophrenia and 41 matched healthy controls. RESULTS: The three-factor (pessimistic repetitive future thinking, repetitive thinking about future goals, and positive indulging about the future) structure of the FoRT scale with one item deleted, fitted the Chinese samples. And the scale could distinguish patients with schizophrenia and individuals with high schizotypal traits from controls. CONCLUSION: These findings support that the Chinese version of the FoRT scale is a valid tool and provide evidence for the potential applications in the schizophrenia spectrum.

Characteristics and immune functions of the endogenous CRISPR-Cas systems in myxobacteria.

The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) system widely occurs in prokaryotic organisms to recognize and destruct genetic invaders. Systematic collation and characterization of endogenous CRISPR-Cas systems are conducive to our understanding and potential utilization of this natural genetic machinery. In this study, we screened 39 complete and 692 incomplete genomes of myxobacteria using a combined strategy to dispose of the abridged genome information and revealed at least 19 CRISPR-Cas subtypes, which were distributed with a taxonomic difference and often lost stochastically in intraspecies strains. The cas genes in each subtype were evolutionarily clustered but deeply separated, while most of the CRISPRs were divided into four types based on the motif characteristics of repeat sequences. The spacers recorded in myxobacterial CRISPRs were in high G+C content, matching lots of phages, tiny amounts of plasmids, and, surprisingly, massive organismic genomes. We experimentally demonstrated the immune and self-target immune activities of three endogenous systems in Myxococcus xanthus DK1622 against artificial genetic invaders and revealed the microhomology-mediated end-joining mechanism for the immunity-induced DNA repair but not homology-directed repair. The panoramic view and immune activities imply potential omnipotent immune functions and applications of the endogenous CRISPR-Cas machinery. IMPORTANCE: Serving as an adaptive immune system, clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) empower prokaryotes to fend off the intrusion of external genetic materials. Myxobacteria are a collective of swarming Gram-stain-negative predatory bacteria distinguished by intricate multicellular social behavior. An in-depth analysis of their intrinsic CRISPR-Cas systems is beneficial for our understanding of the survival strategies employed by host cells within their environmental niches. Moreover, the experimental findings presented in this study not only suggest the robust immune functions of CRISPR-Cas in myxobacteria but also their potential applications.

Development and validation of a prognostic prediction model for cervical cancer patients treated with radical radiotherapy: a study based on TCGA database.

Background: Radiotherapy or concurrent chemoradiotherapy is the standard treatment for patients with locally advanced or inoperable cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, treatment failure for CESC patients treated with radical radiotherapy still occurs due to local recurrence and distant metastasis. The previous prediction models were focused on all CESC patients, neglecting the prognostic differences under different treatment modalities. Therefore, there is a pressing demand to explore novel biomarkers for the prognosis and sensitivity of radiotherapy in CESC patients treated with radical radiotherapy. As a single biomarker has limited effect in stratifying these patients, our objective was to identify radioresponse-related mRNAs to ameliorate forecast of the prognosis for CESC patients treated with radical radiotherapy. Methods: Sample data on CESC patients treated with radical radiotherapy were obtained from The Cancer Genome Atlas (TCGA) database. We randomly separated these patients into a training and test cohorts using a 1:1 ratio. Differential expression analysis was carried out to identify radioresponse-related mRNA sets that were significantly dysregulated between complete response (CR) and radiographic progressive disease (RPD) groups, and univariate Cox regression analyses, least absolute shrinkage and selection operator (LASSO) method and multivariate Cox regression were performed to identify the radioresponse-related signature in the training cohort. we adopted survival analysis to measure the predictive value of the radioresponse-related signature both in the test and entire cohorts. Moreover, we developed a novel nomogram to predict the overall survival (OS) of CESC patients treated with radical radiotherapy. In addition, immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were conducted to preliminarily explore possible mechanisms. Results: This study included a total of 92 CESC patients subjected to radical radiotherapy. We developed and verified a risk score model based on radioresponse-related mRNA. The radioresponse-related mRNA signature and International Federation of Gynecology and Obstetrics (FIGO) stage were served as independent prognostic factors for CESC patients treated with radical radiotherapy. Moreover, a nomogram integrating radioresponse-related mRNA signature with FIGO stage was established to perform better for predicting 1-, 3-, and 5-year survival rates. Mechanically, the low-risk group under the risk score of this model had a better survival status, and the distribution of CD4 T cells was potentially involved in the regulation of radiotherapy response in CESC, leading to a better survival outcome in the low-risk group. Conclusions: This study presents a new radioresponse-related mRNA signature that shows promising clinical efficacy in predicting the prognosis of CESC patients treated with radical radiotherapy.

Oridonin attenuates liver ischemia-reperfusion injury by suppressing PKM2/NLRP3-mediated macrophage pyroptosis.

BACKGROUND: The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti-inflammasome effect, but its effect and mechanisms for liver IRI are still unknown. METHODS: Mice and liver macrophages were treated with Ori, respectively. Co-IP and LC-MS/MS analysis of the interaction between PKM2 and NLRP3 in macrophages. Liver damage was detected using H&E staining. Pyroptosis was detected by WB, TEM, and ELISA. RESULTS: Ori ameliorated liver macrophage pyroptosis and liver IRI. Mechanistically, Ori inhibited the interaction between pyruvate kinase M2 isoform (PKM2) and NLRP3 in hypoxia/reoxygenation（H/R）-induced macrophages, while the inhibition of PKM2/NLRP3 reduced liver macrophage pyroptosis and liver IRI. CONCLUSION: Ori exerted protective effects on liver IRI via suppressing PKM2/NLRP3-mediated liver macrophage pyroptosis, which might become a potential therapeutic target in the clinic.

The role of small RNAs in resistant melon cultivar against Phelipanche aegyptiaca parasitization.

Bidirectional trans-kingdom RNA silencing, a pivotal factor in plant-pathogen interactions, remains less explored in plant host-parasite dynamics. Here, using small RNA sequencing in melon root systems, we investigated microRNA (miRNA) expression variation in resistant and susceptible cultivars pre-and post-infection by the parasitic plant, broomrape. This approach revealed 979 known miRNAs and 110 novel miRNAs across 110 families. When comparing susceptible (F0) and resistant (R0) melon lines with broomrape infection (F25 and R25), 39 significantly differentially expressed miRNAs were observed in F25 vs. F0, 35 in R25 vs. R0, and 5 in R25 vs. F25. Notably, two miRNAs consistently exhibited differential expression across all comparisons, targeting genes linked to plant disease resistance. This suggests their pivotal role in melon's defense against broomrape. The target genes of these miRNAs were confirmed via degradome sequencing and validated by qRT-PCR, ensuring reliable sequencing outcomes. GO and KEGG analyses shed light on the molecular functions and pathways of these differential miRNAs. Furthermore, our study unveiled four trans-kingdom miRNAs, forming a foundation for exploring melon's resistance to broomrape.

Comparisons between Caucasian-validated photo-numeric scales and Korean-validated photo-numeric scales for photo-ageing. Insights from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort.

BACKGROUND: Photo-ageing is a form of skin ageing which affects the entire face. A photo-aged skin has a diverse variety of wrinkles and dyspigmentation all over the face. Here, we discuss photo-ageing on the Chinese skin evaluated using a photo-numeric scale developed and validated on Caucasian skin (i.e., Caucasian scale) and evaluated using a photo-numeric scale developed and validated on Korean skin (i.e., Korean scale). The Korean scale can be subdivided into two scales that separately address the wrinkling and dyspigmentation constituents of photo-ageing. AIM: As there are currently no photo-ageing scales for Chinese skin, the main objective of this study is to adapt existing photo-ageing photo-numeric scales for use on ethnic Chinese skin. METHOD: Three trained assessors studied facial photo-ageing on 1,081 ethnic Chinese young adults from the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) cohort. RESULTS: All assessors are highly internally consistent (Weighted Kappa (κw) values≥0.952). We found that the Caucasian scale and Korean scale give nearly synonymous results for the wrinkling constituent of photo-ageing (R2 = 0.9386). The two scales are strongly concordant (Spearman's Rank Correlation (ρ) value: 0.62 ± 0.06, p = 1.31×10-84). A weak-to-moderate inter-scalar level of agreement (Cohen's Kappa (κ) values: 0.38 ± 0.05, p = 8.87×10-53) persists and is statistically significant after accounting for agreements due to chance. When tested on ethnic Chinese skin, both scales detect photo-ageing consistently (Area under curve [AUC] values: 0.76-0.84). Additionally, the Korean scale for the dyspigmentation constituent of photo-ageing is concordant with both the Caucasian scale (R2 = 0.7888) and the Korean scale for the wrinkling constituent of photo-ageing (R2 = 0.7734). CONCLUSION: Our results show that the Caucasian scale is suitable for capturing photo-ageing on Chinese skin, especially wrinkle variations. The Korean dyspigmentation scale supplements the Caucasian scale to capture dyspigmentation patterns on Chinese skin that may be absent on Caucasian skin. Currently, photo-ageing scales for Chinese skin are absent. When developed, these photo-ageing scales must be properly validated for their ability to capture photo-ageing of the entire face.

Correction: Zhao et al. Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN). Cells 2020, 9, 559.

In the original publication [...].

Comparisons between wrinkles and photo-ageing detected and self-reported by the participant or identified by trained assessors reveal insights from Chinese individuals in the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) cohort.

BACKGROUND: Changes develop on the facial skin as a person ages. Other than chronological time, it has been discovered that gender, ethnicity, air pollution, smoking, nutrition, and sun exposure are notable risk factors that influence the development of skin ageing phenotypes such as wrinkles and photo-ageing. These risk factors can be quantified through epidemiological collection methods. We previously studied wrinkles and photo-ageing in detail using photo-numeric scales. The analysis was performed on the ethnic Chinese skin by three trained assessors. Recent studies have shown that it is possible to use self-reported data to identify skin-related changes including skin colour and skin cancer. In order to investigate the association between risk factors and skin ageing phenotypic outcomes in large-scale epidemiological studies, it would be useful to evaluate whether it is also possible for participants to self-report signs of ageing on their skin. AIM: We have previously identified several validated photo-numeric scales for wrinkling and photo-ageing to use on ethnic Chinese skin. Using these scales, our trained assessors grade wrinkling and photo-ageing with moderately high inter-assessor concordance and agreement. The main objective of this study involves letting participants grade self-reported wrinkling and photo-ageing using these same scales. We aim to compare the concordance and agreement between signs of skin ageing by the participant and signs of ageing identified by our assessors. METHOD: Three trained assessors studied facial photo-ageing on 1081 ethnic Chinese young adults from the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) cohort. Self-reported facial photo-ageing data by the same 1081 participants were also collated and the two sets of data are compared. RESULTS: Here, we found that self-reported signs of photo-ageing are concordant with photo-ageing detected by our assessors. This finding is consistent whether photo-ageing is evaluated through studying wrinkle variations (Spearman's rank correlation (ρ) value: 0.246-0.329) or through studying dyspigmentation patterns (Spearman's rank correlation (ρ) value 0.203-0.278). When studying individual wrinkles, both participants and assessors often detect the presence of the same wrinkle (Spearman's rank correlation (ρ) value 0.249-0.366). A weak-to-fair level of agreement between both participants and assessors (Cohen's kappa (κ) values: 0.041-0.233) persists and is statistically significant after accounting for agreements due to chance. Both the participant and the assessor are largely consistent in evaluating the extent of photo-ageing (area under curve (AUC) values 0.689-0.769) and in discerning between the presence or absence of a given facial wrinkle (area under curve (AUC) values 0.601-0.856). CONCLUSION: When we analyse the overall appearance of the face, our results show that signs of photo-ageing identified by the participant are concordant with signs of photo-ageing identified by our assessors. When we focused our analysis on specific areas of the face, we found that participants were more likely to identify and self-report the same wrinkles that our assessors have also detected. Here, we found that self-reported signs of skin ageing provide a satisfactory approximation to the signs of skin ageing identified by our assessors. The ability to use self-reported signs of skin ageing should also be evaluated on scales beyond the ones discussed in this study. Currently, there are not as many photo-numeric scales for quantifying dyspigmentation patterns as there are for quantifying wrinkle variations. As Chinese skin is known to become dyspigmented more easily with age, more photo-numeric scales need to be developed and properly validated.

Strictosamide promotes wound healing through activation of the PI3K/AKT pathway.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

A rapid and simple non-radioactive assay for measuring uptake by solute carrier transporters.

Introduction: Solute carrier (SLC) transport proteins play a crucial role in maintaining cellular nutrient and metabolite homeostasis and are implicated in various human diseases, making them potential targets for therapeutic interventions. However, the study of SLCs has been limited due to the lack of suitable tools, particularly cell-based substrate uptake assays, necessary for understanding their biological functions and for drug discovery purposes. Methods: In this study, a cell-based uptake assay was developed using a stable isotope-labeled compound as the substrate for SLCs, with detection facilitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay aimed to address the limitations of existing assays, such as reliance on hazardous radiolabeled substrates and limited availability of fluorescent biosensors. Results: The developed assay was successfully applied to detect substrate uptakes by two specific SLCs: L-type amino acid transporter 1 (LAT1) and sodium taurocholate co-transporting polypeptide (NTCP). Importantly, the assay demonstrated comparable results to the radioactive method, indicating its reliability and accuracy. Furthermore, the assay was utilized to screen for novel inhibitors of NTCP, leading to the identification of a potential NTCP inhibitor compound. Discussion: The findings highlight the utility of the developed cell-based uptake assay as a rapid, simple, and environmentally friendly tool for investigating SLCs' biological roles and for drug discovery purposes. This assay offers a safer alternative to traditional methods and has the potential to contribute significantly to advancing our understanding of SLC function and identifying therapeutic agents targeting SLC-mediated pathways.

Myasthenia gravis with tongue muscle atrophy: A case series.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.