Impact of the trans-ancestry polygenic risk score on type 2 diabetes risk, onset age and progression among population in Taiwan.

Type 2 diabetes (T2D) prevalence in adults at a younger age has increased but the disease status may go unnoticed. This study aimed to determine whether the onset age and subsequent diabetic complications can be attributed to the polygenic architecture of T2D in the Taiwan Han population. A total of 9,627 cases with T2D and 85,606 controls from the Taiwan Biobank were enrolled. Three diabetic polygenic risk scores (PRSs), PRS_EAS and PRS_EUR, and a trans-ancestry PRS (PRS_META), calculated using summary statistic from East Asian and European populations. The onset age was identified by linking to the National Taiwan Insurance Research Database, and the incidence of different diabetic complications during follow-up was recorded. PRS_META (7.4%) explained a higher variation for T2D status. And the higher percentile of PRS is also correlated with higher percentage of T2D family history and prediabetes status. More, the PRS was negatively associated with onset age (ß = -0.91 yr), and this was more evident among males (ß = -1.11 vs. -0.76 for males and females, respectively). The hazard ratio of diabetic retinopathy (DR) and diabetic foot were significantly associated with PRS_EAS and PRS_META, respectively. However, the PRS was not associated with other diabetic complications, including diabetic nephropathy, cardiovascular disease, and hypertension. Our findings indicated that diabetic PRS which combined susceptibility variants from cross-population could be used as a tool for early screening of T2D, especially for high-risk populations, such as individuals with high genetic risk, and may be associated with the risk of complications in subjects with T2D. NEW & NOTEWORTHY Our findings indicated that diabetic polygenic risk score (PRS) which combined susceptibility variants from Asian and European population affect the onset age of type 2 diabetes (T2D) and could be used as a tool for early screening of T2D, especially for individuals with high genetic risk, and may be associated with the risk of diabetic complications among people in Taiwan.

Ubiquitination-specific protease 7 enhances stemness of hepatocellular carcinoma by stabilizing basic transcription factor 3.

This study aims to explore the molecular regulation mechanism of ubiquitination-specific protease 7 (USP7) in facilitating the stemness properties of hepatocellular carcinoma (HCC). Gain-of-function and loss-of-function assays were conducted in SK-Hep1 and HepG2 cells transfected with USP7 overexpression/knockdown plasmids and USP7 inhibitor P22077. The proliferation, migration, invasion, and self-renewal capacity of hepatocellular carcinoma cells were detected by CCK-8, colony formation, Transwell, scratch, and tumor sphere formation, respectively. MS was performed to identify the potential substrate of USP7 following P22077 treatment. Co-IP assay was used to verify the interaction between USP7 and basic transcription factor 3 (BTF3) in HCC cells. The overexpression of USP7 could promote the proliferation, migration, invasion, and colony formation capacity of SK-Hep1 and HepG2 cells. Additionally, ectopic UPS7 enhanced the epithelial-mesenchymal transition (EMT) and stem-like characteristics of the HCC cells. In contrast, USP7 depletion by knockdown of USP7 or administrating inhibitor P22077 significantly inhibited these malignant phenotypes of SK-Hep1 and HepG2 cells. Following MS analysis, BTF3 was identified as a potential substrate for USP7. USP7 could interact with BTF3 and upregulate its protein level, while USP7 depletion significantly upregulated the ubiquitination levels. Overexpression of BTF3 partially rescue the inhibitory effects of USP7 depletion on the malignant phenotypes and stemness properties of SK-Hep1 and HepG2 cells. USP7 can promote the stemness and malignant phenotype of HCC by stabilizing BTF3.

Tumor-intrinsic IFNα and CXCL10 are critical for immunotherapeutic efficacy by recruiting and activating T lymphocytes in tumor microenvironment.

Tumor immunotherapies targeting PD-(L)1 exhibit anti-tumor efficacy in only 10-30% of patients with various cancers. Literature has demonstrated that a "hot tumor" which contains high T lymphocytes in the tumor microenvironment exhibits a better response to immunotherapies than a "cold tumor." This study aimed to investigate whether tumor-intrinsic IFNα and CXCL10 determine the recruitment and activation of CD8+ T cells to become "hot tumor." In this study, we found that CXCL10 overexpressed in a variety of tumors including lung, colon, and liver tumors with a correlation with PD-L1. High PD-L1 and CXCL10 are associated with better survival rates in tumor patients receiving immunotherapies. IFNs-downstream transcriptional factor IRF-1 and STAT1 were correlated with PD-L1 and CXCL10 expression. We demonstrated that IRF-1 and STAT1 were both bound with the promoters of PD-L1 and CXCL10, sharing the same signaling pathway and determining IFNs-mediated PD-L1 and CXCL10 expression. In addition, IFNα significantly increased activation marker IFNγ in PBMCs, promoting M1 type monocyte differentiation, CD4+ T, and CD8+ T cell activation. Particularly, we found that CD8+ T lymphocytes abundantly expressed CXCR3, a receptor of CXCL10, by flow cytometry, indicating that tumor-intrinsic CXCL10 potentially recruited CD8+ T in tumor microenvironment. To demonstrate the hypothesis, immunotherapy-sensitive CT26 and immunotherapy-resistant LL/2 were used and we found that CT26 cells exhibited higher IFNα, IFNγ, CXCL10, and PD-L1 levels compared to LL/2, leading to higher IFNγ expression in mouse splenocytes. Moreover, we found that CD8+ T cells were recruited by CXCL10 in vitro, whereas SCH546738, an inhibitor of CXCR3, inhibited T cell migration and splenocytes-mediated anti-tumor effect. We then confirmed that CT26-derived tumor was sensitive to αPD-L1 immunotherapy and LL/2-tumor was resistant, whereas αPD-L1 significantly increased T lymphocyte activation marker CD107a in CT26-derived BALB/c mice. In conclusion, this study revealed that CXCL10 expression is correlated with PD-L1 in tumors, sharing the same signaling pathway and associating with better immunotherapeutic efficacy. Further evidence in the syngeneic tumor models demonstrated that immunotherapy-sensitive CT26 intrinsically exhibited higher IFNα and CXCL10 compared to immunotherapy-resistant LL/2 to recruit and activate CD8+ T cells in the tumor microenvironment, exhibiting "hot tumor" characteristic of sensitizing αPD-L1 immunotherapies.

Application of bulk segregant RNA-Seq (BSR-Seq) and allele-specific primers to study soybean powdery mildew resistance.

BACKGROUND: Powdery mildew (PM) is one of the important soybean diseases, and host resistance could practically contribute to soybean PM management. To date, only the Rmd locus on chromosome (Chr) 16 was identified through traditional QTL mapping and GWAS, and it remains unclear if the bulk segregant RNA-Seq (BSR-Seq) methodology is feasible to explore additional PM resistance that might exist in other varieties. RESULTS: BSR-Seq was applied to contrast genotypes and gene expressions between the resistant bulk (R bulk) and the susceptible bulk (S bulk), as well as the parents. The ∆(SNP-index) and G' value identified several QTL and significant SNPs/Indels on Chr06, Chr15, and Chr16. Differentially expressed genes (DEGs) located within these QTL were identified using HISAT2 and Kallisto, and allele-specific primers (AS-primers) were designed to validate the accuracy of phenotypic prediction. While the AS-primers on Chr06 or Chr15 cannot distinguish the resistant and susceptible phenotypes, AS-primers on Chr16 exhibited 82% accuracy prediction with an additive effect, similar to the SSR marker Satt431. CONCLUSIONS: Evaluation of additional AS-primers in the linkage disequilibrium (LD) block on Chr16 further confirmed the resistant locus, derived from the resistant parental variety 'Kaohsiung 11' ('KS11'), not only overlaps with the Rmd locus with unique up-regulated LRR genes (Glyma.16G213700 and Glyma.16G215100), but also harbors a down-regulated MLO gene (Glyma.16G145600). Accordingly, this study exemplified the feasibility of BSR-Seq in studying biotrophic disease resistance in soybean, and showed the genetic makeup of soybean variety 'KS11' comprising the Rmd locus and one MLO gene.

Increased risk of psychiatric disorder in patients with hearing loss: a nationwide population-based cohort study.

BACKGROUND: Hearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time. METHODS: This was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The Kaplan‒Meier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders. RESULTS: A total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P < 0.001). Multivariate analysis indicated that hearing loss significantly elevated the risk of psychiatric disorders (adjusted HR = 2.587, 95% CI 1.723-3.346, p < 0.001). CONCLUSION: Our findings indicate that patients with hearing loss are more likely to develop psychiatric disorders. Furthermore, the various psychiatric disorders are more likely to occur at different times. Our findings have important clinical implications, including a need for clinicians to implement early intervention for hearing loss and to pay close attention to patients' psychological status. Trial registration TSGHIRB No. E202216036.

Concurrent administration of serotonergic antidepressants and ozanimod in participants with relapsing multiple sclerosis from the open-label extension DAYBREAK trial.

BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.

Synthesis of Diarylamines via Nitrosonium-Initiated C-N Bond Formation.

Electron-rich diarylamines, exemplified by anisole-derived amines, play pivotal roles in process chemistry, pharmaceuticals, and materials. In this study, homo-diarylamines were synthesized directly from the C-H activation of electron-rich arenes by sodium nitrate/trifluoroacetic acid and the successive treatment of iron powder. Mechanistic investigations reveal that nitrosoarene serves as the reaction intermediate, and the formation of the second C-N bond between the resulting nitrosoarene and electron-rich arene is catalyzed by the nitrosonium ion (NO+). Thus, hetero-diarylamines were synthesized using preformed nitrosoarenes and various electron-rich arenes. This reaction complements a range of cross-coupling reactions catalyzed by transition metal catalysts.

Risks of Glaucoma among Individuals with Psoriasis: A Population-based Cohort Study.

BACKGROUND: Psoriasis is a chronic systemic disorder with ocular involvement. OBJECTIVES: The aim of the present study is to evaluate the risk of glaucoma among psoriatic patients. METHODS: Subjects of this cohort study were selected based on Chang Gung Research Database from January 1, 2003, to December 31, 2012. Follow-up ended on December 31, 2017. The participants of the control group were matched with the psoriatic group by gender, age, and index date at a 4:1 ratio. The hazard ratios of glaucoma were estimated using Cox regression analysis. We also evaluated the relationship between the risk of glaucoma and systemic therapies as well as phototherapy and topical corticosteroid in patients with psoriasis. RESULTS: A total of 6,682 patients with psoriasis and 26,728 matched controls were enrolled. The study population is composed of mainly Males accounting for 64.2% of the study population. The psoriatic group had higher incidence rates than the control group for glaucoma (adjusted hazard ratio 1.405 [95% confidence interval, 1.051-1.879]). Psoriatic patients receiving psoralen and ultraviolet-A (PUVA) therapy for more than 200 sessions had an increased risk of glaucoma. CONCLUSIONS: Psoriatic patients had an increased risk of glaucoma. Long-term PUVA therapy raised the risk of glaucoma in psoriatic populations.

Multiplexed transcriptional profiling of Dermatophagoides house dust mites allergens in human epithelium cells.

Allergic asthma, a chronic disease characterized by airway inflammation, poses a significant public health concern. It is well-established that house dust mites (HDMs) are common inducers of allergic responses in individuals, particularly children. In central Taiwan, our research team observed that over 80% of allergic children exhibited sensitization to various HDMs species. This investigation aims to bridge the gap between these observations and a better understanding of the early fundamental mechanisms for preventing allergic diseases. Specifically, our study delves into the impact of crude extracts of HDMs on human epithelial BEAS-2B cells. Our findings, based on RNA sequencing (RNA-seq) analysis, shed light on how three major Dermatophagoides HDMs allergens activate a common Toll-like receptor signaling pathway in human epithelial cells within a 4-h treatment. During this process, the nuclear transcription factor NF-κB translocated into the cell nucleus within 30 min of allergen stimulation, triggering the expression of pro-inflammatory genes such as IL-6 and IL-8 over 4 h. Additionally, when the cells were treated with specific Dermatophagoides microceras (Der m) allergens, it resulted in the upregulation of genes that regulate type 1 diabetes mellitus (T1DM) signaling pathways. This led to the mediation of IL-12A inflammation. Furthermore, there was an increase in gene sets associated with cilia function and the microtubule cytoskeleton in human epithelial cells after treatment with a combination of Der m allergens and Dexamethasone. Additionally, OMICs analysis was conducted to examine the effects of HDMs allergenic stimulation on human epidermal cells. We aimed to improve our understanding of the molecular mechanisms within cells and identify potential targets and natural products in the treatment of asthma caused by HDMs allergens.

Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

Failure of the linkage mechanism in a semi-constrained total elbow arthroplasty is a rare and unpredictable event: a review of seven cases.

PURPOSE: Linked component of total elbow arthroplasty (TEA) consisted of bushing and locking pins. Failure of linked components is a rare complication of TEA. This study aims to investigate the mechanism and consequence of failure of the linkage mechanism in TEA surgeries. METHODS: Between 2010 and 2021, five patients received revision operation due to linked component failure. Besides, two patients underwent primary operation at another institute were also analyzed due to failure of the linkage mechanism. RESULTS: All seven patients underwent primary TEA and mean age for primary TEA was 48 (range, 27-62). Two patients had TEA for post-traumatic arthritis, three patients for rheumatoid arthritis, and two patients for comminuted distal humerus fracture. The average time between primary TEA and revision TEA for linked component failure was 13.6 years. Three bushing wear and four locking pin dissociation were diagnosed according to pre-operative radiography. Elbow pain and swelling are the most common clinical symptoms. Severe osteolysis, periprosthetic fracture, and stem loosening were noted in three bushing wear cases. In four dissociation of locking pin cases, breakage of male locking pin phalanges was demonstrated in two patients. For revision procedures, both the locking pins and bushings were replaced. No patients in the study required additional surgery after the revision operation for linked component failure. CONCLUSION: Osteolysis, component loosening, periprosthetic fracture may be expected after linked component failure. Patients should be regularly followed up from short-term to long-term with radiography. Early diagnosis and intervention with linked component exchange can prevent extensive revision surgery.

Platelet-Rich Plasma Versus Platelet-Poor Plasma for Treating Facial Photoaging: a Double-Blind Randomized Controlled Splitting Face Study.

BACKGROUND: As the demand for non-invasive esthetic procedures to maintain a youthful appearance increases, there has been growing interest in the use of autologous platelet-rich plasma (PRP) and platelet-poor plasma (PPP) for the treatment of facial aging. However, there are few studies directly comparing the efficacy of PRP and PPP for facial rejuvenation. OBJECTIVES: This study aimed to compare the efficacy of PRP and PPP for facial rejuvenation. METHODS: This single-center, double-blind, randomized controlled trial was conducted from January 1, 2022, to July 31, 2022, and included ten participants who completed the follow-up. The participants were randomly assigned to receive 2.5-mL injections of PRP and PPP on different sides of the face in three sessions with 1-month intervals. The outcome was primarily determined by blinded photographic assessments and secondly by scores of the VISIA® system during the follow-up. RESULTS: Both PRP and PPP treatments resulted in significant improvement in the Global Aesthetic Improvement Scales and Modified Fitzpatrick Wrinkle Scale for periocular Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation wrinkles, with no significant difference between the two groups. However, no improvement was observed in the Wrinkle Severity Rating Scales for nasolabial folds in either the PRP- or PPP-treated groups. Furthermore, no severe adverse events were reported. CONCLUSIONS: Both PRP and PPP are effective in treating facial photoaging. PRP exhibited slightly superior efficacy in enhancing overall skin condition, while PPP was slightly more effective in improving shallow wrinkles. This study provides valuable evidence for the use of PRP and PPP in facial rejuvenation procedures. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of exercise on depression in patients with rheumatic diseases: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of exercise intervention on depression in rheumatic diseases by means of a meta-analysis. METHODS: The Cochrane Library, Embase, Medline, PubMed, and relevant records were searched. The qualities of randomized controlled trials were evaluated. Meta-analysis of the obtained related data was completed using RevMan 5.3. Heterogeneity was also evaluated with χ2 test and I2. RESULTS: Twelve RCTs were reviewed. Compared with baseline, the meta-analysis results showed that there was significant difference in the improvement of depression assessed by HADs, BDI, CES­D, and AIMS in patients with rheumatic diseases (post exercise vs. baseline, -0.73 [-1.05, -0.4], P < 0.0001, I2 = 0%). In subgroup analysis, although none of these trends in BDI and CES­D subgroups were significant at P < 0.05, there were clear trends towards improvement in depression. CONCLUSION: As an alternative or supplementary treatment, the effect of exercise on rheumatism is obvious. Rheumatologists can consider exercise as an integral part of the treatment of patients with rheumatism.

Impact of Foodborne Disease in Taiwan during the COVID-19 Pandemic.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic originated in Wuhan, China, in December 2019, the first case diagnosed since January 2020 in Taiwan. The study about the potential impact of the COVID-19 pandemic on event, location, food source, and pathogens of foodborne disease (FBD) is limited in Taiwan. Our aim in this study is to investigate FBD in the context of the COVID-19 pandemic. Materials and Methods: We collected publicly available annual summary data from the FBD dataset in the Taiwan Food and Drug Administration and Certifiable Disease on reported FBD in Taiwan from 2019 to 2020. We used logistic regression to evaluate changes in the occurrence or likelihood of FBD cases and Poisson regression to examine the relative risk (RR) between FBD and climate factors. Results: Similar events occurred in 2019 and 2020, but the total number of FBD cases decreased from 6935 in 2019 to 4920 in 2020. The places where FBD decreased were in schools, hospitals, outdoors, vendors, and exteriors. The top place in FBD shifted from schools to restaurants. The top food source for FBD has changed from boxed food to compound food. Bacillus cereus and Salmonella emerged as the top two observed bacterial pathogens causing FBD. The risk of FBD cases increased with a higher air temperature, with an RR of 1.055 (1.05-1.061, p < 0.001) every 1 °C. Conclusion: The incidence of FBD decreased significantly during the COVID-19 pandemic in Taiwan. This decline may be attributed to protective measures implemented to control the spread of the virus. This shift in locations could be influenced by changes in public behavior, regulations, or other external factors. The study emphasizes the importance of understanding the sources and effectiveness of severe infection prevention policies. The government can use these findings to formulate evidence-based policies aimed at reducing FBD cases and promoting public health. Consumers can reduce the risk of FBD by following safe food handling and preparation recommendations.

The Association between Cafestol and Cardiovascular Diseases: A Comprehensive Review.

Cafestol, a bioactive compound found in coffee, has attracted considerable attention due to its potential impact on cardiovascular health. This review aims to comprehensively explore the association between cafestol and cardiovascular diseases. We delve into the mechanisms through which cafestol influences lipid metabolism, inflammation, and endothelial function, all of which are pivotal in cardiovascular pathophysiology. Moreover, we meticulously analyze epidemiological studies and clinical trials to elucidate the relationship between cafestol and cardiovascular outcomes. Through a critical examination of existing literature, we aim to provide insights into the potential benefits and risks associated with cafestol concerning cardiovascular health.

Radiotherapy enhances CXCR3highCD8+ T cell activation through inducing IFNγ-mediated CXCL10 and ICAM-1 expression in lung cancer cells.

Radiotherapy (RT) not only damages tumors but also induces interferon (IFN) expression in tumors. IFNs mediate PD-L1 to exhaust CD8+ T cells, but which also directly impact tumor cells and potentially activate anti-tumor immune surveillance. Little is known about the contradictory mechanism of IFNs in regulating CD8+ T-mediated anti-tumor activity in lung cancer. This study found that RT induced IFNs and CXCL9/10 expression in the RT-treated lung cancer cells. Specifically, RT- and IFNγ-pretreated A549 significantly activated CD8+ T cells, resulting in significant inhibition of A549 colony formation. RNAseq and consequent qPCR results revealed that IFNγ induced PD-L1, CXCL10, and ICAM-1, whereas PD-L1 knockdown activated CD8+ T cells, but ICAM-1 knockdown diminished CD8+ T cell activation. We further demonstrated that CXCR3 and CXCL10 decreased in the CD8+ T cells and nonCD8+ PBMCs, respectively, in the patients with lung cancer that expressed lower reactivation as co-cultured with A549 cells. In addition, inhibitors targeting CXCR3 and LFA-1 in CD8+ T cells significantly diminished CD8+ T cell activation and splenocytes-mediated anti-LL/2shPdl1. In conclusion, we validated that RT suppressed lung cancer and overexpress PD-L1, CXCL10, and ICAM-1, which exhibited different roles in regulating CD8+ T cell activity. We propose that CXCR3highCD8+ T cells stimulated by CXCL10 exhibit anti-tumor immunity, possibly by enhancing T cells-tumor cells adhesion through CXCL10/CXCR3-activated LFA-1-ICAM-1 interaction, but CXCR3lowCD8+ T cells with low CXCL10 in patients with lung cancer were exhausted by PD-L1 dominantly. Therefore, RT potentially activates CD8+ T cells by inducing IFNs-mediated CXCL10 and ICAM-1 expression in tumors to enhance CD8+ T-tumor adhesion and recognition. This study clarified the possible mechanisms of RT and IFNs in regulating CD8+ T cell activation in lung cancer.

Near infrared imaging system for preventing blood vision obstruction in endoscopy.

Spinal endoscopy procedure is commonly used in the diagnosis and treatment of various health problems and is effective. Bleeding is one of the most common complications of spinal endoscopy procedures. Blood vision obstruction (BVO), that is, obstruction of the endoscopic camera lens caused by the accumulation of blood in the surgical field, is a serious problem in endoscopic procedures. This study presents what we believe to be a new approach to addressing BVO with external multispectral imaging. The study was completed using a BVO simulation model, and the results reveal that this technology can be used to effectively overcome BVO and provide clear images of the anatomy, enabling more effective diagnosis and treatment. This technique may enable improvement of the outcomes of endoscopic procedures and could have far-reaching implications in the field of endoscopy.

Associations of genetic markers of diabetes mellitus with carotid atherosclerosis: a community-based case-control study.

BACKGROUND: Diabetes mellitus (DM) is a well-established determinant of atherosclerosis and cardiovascular diseases (CVD). Recently, genome-wide association studies (GWAS) identified several single nucleotide polymorphism (SNP) significantly correlated with DM. The study aimed to explore the relationships of the top significant DM SNPs with carotid atherosclerosis (CA). METHODS: We used a case-control design and randomly selected 309 cases and 439 controls with and without, respectively, carotid plaque (CP) from a community-based cohort. Eight recent GWAS on DM in East Asians reported hundreds of SNPs with genome-wide significance. The study used the top significant DM SNPs, with a p-value < 10-16, as the candidate genetic markers of CA. The independent effects of these DM SNPs on CA were assessed by multivariable logistic regression analyses to control the effects of conventional cardio-metabolic risk factors. RESULTS: Multivariable analyses showed that, 9 SNPs, including rs4712524, rs1150777, rs10842993, rs2858980, rs9583907, rs1077476, rs7180016, rs4383154, and rs9937354, showed promising associations with the presence of carotid plaque (CP). Among them, rs9937354, rs10842993, rs7180016, and rs4383154 showed significantly independent effects. The means (SD) of the 9-locus genetic risk score (9-GRS) of CP-positive and -negative subjects were 9.19 (1.53) and 8.62 (1.63), respectively (p < 0.001). The corresponding values of 4-locus GRS (4-GRS) were 4.02 (0.81) and. 3.78 (0.92), respectively (p < 0.001). The multivariable-adjusted odds ratio of having CP for per 1.0 increase in 9-GRS and 4-GRS were 1.30 (95% CI 1.18-1.44; p = 4.7 × 10-7) and 1.47 (95% CI 1.74-9.40; p = 6.1 × 10-5), respectively. The means of multi-locus GRSs of DM patients were similar to those of CP-positive subjects and higher than those of CP-negative or DM-negative subjects. CONCLUSIONS: We identified 9 DM SNPs showing promising associations with CP. The multi-locus GRSs may be used as biomarkers for the identification and prediction of high-risks subjects for atherosclerosis and atherosclerotic diseases. Future studies on these specific SNPs and their associated genes may provide valuable information for the preventions of DM and atherosclerosis.

MFI2 upregulation promotes malignant progression through EGF/FAK signaling in oral cavity squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the predominant histological type of the head and neck squamous cell carcinoma (HNSCC). By comparing the differentially expressed genes (DEGs) in OSCC-TCGA patients with copy number variations (CNVs) that we identify in OSCC-OncoScan dataset, we herein identified 37 dysregulated candidate genes. Among these potential candidate genes, 26 have been previously reported as dysregulated proteins or genes in HNSCC. Among 11 novel candidates, the overall survival analysis revealed that melanotransferrin (MFI2) is the most significant prognostic molecular in OSCC-TCGA patients. Another independent Taiwanese cohort confirmed that higher MFI2 transcript levels were significantly associated with poor prognosis. Mechanistically, we found that knockdown of MFI2 reduced cell viability, migration and invasion via modulating EGF/FAK signaling in OSCC cells. Collectively, our results support a mechanistic understanding of a novel role for MFI2 in promoting cell invasiveness in OSCC.

Intrinsic Nonlinear Hall Effect and Gate-Switchable Berry Curvature Sliding in Twisted Bilayer Graphene.

Though the observation of the quantum anomalous Hall effect and nonlocal transport response reveals nontrivial band topology governed by the Berry curvature in twisted bilayer graphene, some recent works reported nonlinear Hall signals in graphene superlattices that are caused by the extrinsic disorder scattering rather than the intrinsic Berry curvature dipole moment. In this Letter, we report a Berry curvature dipole induced intrinsic nonlinear Hall effect in high-quality twisted bilayer graphene devices. We also find that the application of the displacement field substantially changes the direction and amplitude of the nonlinear Hall voltages, as a result of a field-induced sliding of the Berry curvature hotspots. Our Letter not only proves that the Berry curvature dipole could play a dominant role in generating the intrinsic nonlinear Hall signal in graphene superlattices with low disorder densities, but also demonstrates twisted bilayer graphene to be a sensitive and fine-tunable platform for second harmonic generation and rectification.