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This research paper presents empirical evidence aimed at establishing a causal relationship between explicit critical thinking skills and adolescent-parent career congruence among undergraduate students. Additionally, it seeks to identify the mediating role of friendship quality in this relationship. The study employs structural equation modeling as a method to establish causality. The findings of this research have implications for educators and instructors in higher education, as well as career exploration consultants in schools. The study provides valuable evidence on the most effective approach to promoting adolescent-parent career congruence by utilizing critical thinking skills and fostering high-quality friendships.

Abstract Background Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. Objective To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. Methods This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris. Results A total of 1617 patients were enrolled. At week 12, patients in the adapalene–clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (− 66.85%), compared with adapalene alone (− 50.82%) or clindamycin gel alone (− 57.61%). The difference in the least square means of the adapalene–clindamycin gel group and adapalene group, or clindamycin gel group was − 16.08% (95% CI − 19.95% to − 12.21%) and − 9.38% (95% CI − 13.25% to − 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene–clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Conclusion Adapalene 0.1%–clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. Trial Registration ClinicalTrials.gov identifier NCT03615768.

Abstract Lytic induction therapy was devised to selectively combat malignancies associated with Epstein–Barr virus (EBV) by triggering viral reactivation from latency. At present, the major challenges of lytic induction therapy are to maximize reactivating efficiencies and meanwhile minimize infectious virion production. C210, a novel curcumin derivative with potent Hsp90 inhibitory activity, was explored for EBV-reactivating and virion-producing effects in EBV-positive nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC) cell lines. And the molecular mechanisms underlying these effects were determined. Follow C210 treatment, EBV lytic RNAs and proteins were upregulated, but infectious virions were not produced. Knockdown of heat shock protein 90 (Hsp90) induced expression of lytic RNAs and proteins, and diminished C210-driven EBV lytic induction. Pretreatment with an X box binding protein 1 (XBP1) inhibitor reduced C210-induced EBV lytic RNA. Furthermore, we demonstrated that C210 inhibited the binding of Hsp90 with its clients, signal transducer and activator of transcription 3 (STAT3) and xeroderma pigmentosum group B-complementing protein (XPB), which subsequently promoted their proteasomal degradation. Degradation of STAT3 by C210 enhanced the EBV-reactivating and anticancer capacity of suberoylanilide hydroxamic acid (SAHA). Depletion of XPB blocked SAHA-induced expression of late viral genes and production of infectious virions. These results elucidate a novel Hsp90 inhibitor targeting EBV lytic phase and extend the research on lytic induction strategy, which may offer reference value in the treatment of EBV-positive malignancies.

Objective: We present prenatal diagnosis of a 14-Mb 11p11.2-p13 deletion by chromosome microarray analysis (CMA) in a pregnancy with fetal recombinant chromosome 11 syndrome of rec(11)del(11) (p11.2p13)ins(11) (q21p11.2p13) and maternal intrachromosomal insertion of ins(11) (q21p11.2p13). Case Report: A 25-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of a family history of psychiatric disorders in her two brothers and one maternal uncle. Array comparative genomic hybridization (aCGH) analysis of amniocentesis revealed a 14-Mb 11p13p11.2 deletion. The pregnancy was terminated at 19 weeks of gestation, and a 252-g fetus was delivered. Cytogenetic analysis of the parental bloods and cord blood revealed a karyotype of 46,XX,ins(11) (q21p11.2p13) in the mother, 46,XY in the father and 46,XY,rec(11)del(11) (p11.2p13)ins(11) (q21p11.2p13) in the fetus. aCGH analysis on the DNA extracted from cord blood revealed the result of arr 11p13q11.2 (32,697,424–46,712,173) × 1.0 [GRCh37] with a 14-Mb deletion of 11p13-p11.2 encompassing 54 OMIM genes including PHF21A, ALX4, EXT2 and SLC1A2. Polymorphic DNA marker analysis showed a maternal origin of the 11p deletion. The present case had an 11p13-p11.2 deletion encompassing 11p12-p11.3 which is associated with Potocki-Shaffer syndrome (PSS) or chromosome 11p11.2 deletion syndrome. Conclusion: CMA is useful for prenatal detection of fetal genomic imbalance in case of familial intrachromosomal insertion.

Objective: We present first-trimester application of expanded non-invasive prenatal testing (NIPT) in the genetic investigation of fetal 1p36 deletion syndrome associated with a familial unbalanced reciprocal translocation of 46,XX,der(1)t(1;2) (p36.2;q37.3)dmat. Case report: A 37-year-old, gravida 2, para 0, woman underwent expanded NIPT at 13 weeks of gestation because of advanced maternal age and the fear of complications of invasive procedures of prenatal diagnosis. She had experienced one spontaneous abortion. The pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET) because of tubal occlusion. NIPT was positive for 1p36 deletion. At 17 weeks of gestation, she underwent amniocentesis but intrauterine fetal death occurred after amniocentesis and the pregnancy was terminated. Amniocentesis revealed a derivative chromosome 1 with an aberrant short arm terminal segment of chromosome 1. Subsequent cytogenetic analysis of parental bloods showed a karyotype of 46,XY in the father and a karyotype of 46,XX,t(1;2) (p36.2;q37.3) in the mother. The karyotype of amniocytes was 46,XX,der(1)t(1;2) (p36.2;q37.3)dmat, consistent with partial monosomy 1p (1p36.2→pter) and partial trisomy 2q (2q37.3→qter). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed the result of arr 1p36.33p36.22 (852,863–11,303,452) × 1.0 and arr 2q37.3 (242,785,405–243,068,396) × 3.0 [GRCh 37] with a 10.451-Mb deletion of 1p36.33-p36.22 encompassing 116 OMIM genes including RERE and a 283-kb duplication of 2q37.3 encompassing one OMIM gene of PDCD1. Conclusion: Expanded NIPT has the advantage of early detection of familial unbalanced reciprocal translocation in the fetus.

Objective: We present prenatal diagnosis of Jacobsen syndrome associated with a distal 11q deletion and a distal 8q duplication by chromosome microarray analysis (CMA) in a fetus with multiple congenital anomalies on fetal ultrasound. Case Report: A 41-year-old, gravida 2, para 1, woman underwent amniocentesis at 25 weeks of gestation because of intrauterine growth restriction, endocardial cushion defect, clenched hands, arthrogryposis, rocker bottom feet and craniosynostosis on fetal ultrasound. Amniocentesis revealed a karyotype of 46,XX,add(11)(q23.3). Array comparative genomic hybridization (aCGH) analysis of the DNA extracted from the uncultured amniocytes revealed the result of arr 8q24.13q24.3 × 3, 11q23.3q25 × 1. Analysis of FGFR2 revealed no mutation. The karyotype was 46,XX,der(11)t(8;11)(q24.13;q23.3). The parental karyotypes were normal. The pregnancy was subsequently terminated, and a dead malformed fetus was delivered with craniofacial dysmorphism of low-set malformed ears, depressed nasal bridge, hypertelorism, small mouth, clenched hands and rocker bottom feet. Cytogenetic analysis of the placenta revealed a karyotype of 46,XX,der(11)t(8;11)(q24.13;q23.3). aCGH analysis of the DNA extracted from the umbilical cord showed the result of arr 8q24.13q24.3 (126,302,369–146,280,020) × 3.0, arr 11q23.3q25 (120,469,928–134,868,407) × 1.0 [GRCh37] with a 19.978-Mb duplication of 8q24.13-q24.3 and a 14.398-Mb deletion of 11q23.3-q25 encompassing the genes of BSX, ETS1, FLI1 and ARHGAP32. Conclusion: CMA is useful for detection of de novo chromosomal rearrangement in the fetus with multiple congenital anomalies on fetal ultrasound.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disorder affecting the vulvar region. VLS predominantly affects women, and most cases occur after menopause. Common symptoms include itching, skin-whitening, pain, discomfort, fissures, and scarring. Treatment options include topical steroids, emollients, lifestyle modifications, regular follow-up, and surgical interventions. Carbon dioxide (CO2) laser treatment is a therapeutic option for managing lichen sclerosus. We report a case of VLS successfully treated with a fractional microablative CO2 laser. A 72-year-old female presented with a dry vagina and vulvar itching for 6 months. She visited a local medical clinic, and oral anti-itching medication and topical anti-itching ointment were administered. However, the condition did not improve, and she felt itching. She visited our outpatient department, and a pelvic examination showed bilateral labia minor, revealing a white skin color change and a hardening sensation. The patient was diagnosed with VLS. Microablative fractional CO2 laser therapy was subsequently administered. The treatment course comprised three laser therapy sessions (treatment day, 1 month, and 2 months after the first therapy). The vulvovaginal symptoms questionnaire-21 scores were 14, 6, and 2 for the first, second, and third courses of treatment, respectively. Vulvar itching improved significantly after laser treatment – no more steroid treatment needed. After 10 months of follow-up, the condition of the vulva was maintained well. Although the treatment protocol requires further exploration, CO2 laser treatment could be considered for VLS if topical steroids are ineffective.

AIM: To evaluate the visual outcomes of standard amblyopic treatment add-on training via perceptual learning in refractive amblyopic children and to identify the risk factors for treatment failure. METHODS: Retrospective charts were reviewed in children with refractive amblyopia who received standard treatment and add-on Cambridge Visual Stimulator (CAM) training. The add-on CAM group that was enrolled had worn full-corrected glasses for at least 2mo before training. A control group received only the standard treatment. Treatment success was defined as best-corrected visual acuity (BCVA) ≥20/25. The age, sex, initial BCVA, refractive errors, sessions and duration of training, and final BCVA were recorded. RESULTS: A total of 209 children (129 children in add-on CAM group and 80 children in control group) were enrolled. Seventy-six percent of unilateral and 87% of bilateral amblyopic children achieved treatment success. In children with unilateral or bilateral moderate amblyopia, the duration to reach BCVA ≥20/25 was significantly shorter in add-on CAM group than in control group. Poor initial BCVA (P

Abstract In a multicenter case–control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA’s capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.

Objective: We present mosaic distal 13q duplication due to mosaic unbalanced translocation 46,XY,der(14)t(13;14)(q32.2;p13)/46,XY at amniocentesis in a pregnancy associated with a favorable fetal outcome. Case report: A 37-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, add(14) (p13)[17]/46,XY[13] (56.6% mosaicism). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr 13q32.2q34 × 2∼3, consistent with 45% mosaicism for distal 13q duplication. Repeat amniocentesis at 24 weeks of gestation revealed a karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[16] (46.6% mosaicism). The parental karyotypes were normal. aCGH analysis on the DNA extracted from uncultured amniocytes revealed arr 13q32.2q34 × 2.38, consistent with 30–40% mosaicism for distal 13q duplication. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected 22.8% (23/101 cells) mosaicism for distal 13q duplication. Prenatal ultrasound findings were unremarkable. At 39 weeks of gestation, a 3616-g phenotypically normal baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,der(14)t(13;14)(q32.2;p13)[20]/46,XY[20] (50% mosaicism), 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[26] (35% mosaicism) and 46,XY (40/40 cells) (0% mosaicism), respectively. When follow-ups at the age of 4½ months and the age of one year, the peripheral blood had the karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[18]/46,XY[22] (45% mosaicism). Interphase FISH analysis on buccal mucosal cells at the age of 4½ months revealed 2.7% (3/110 cells) mosaicism for distal 13q duplication, compared with 1% (1/100 cells) in the normal control. The neonate was normal in phenotype and development. Conclusions: Mosaic unbalanced translocation at amniocentesis can be associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.

為解決複雜的教學問題，需培養教師具備高階認知層次的能力，而日新月異的人工智慧有望成為師資養成的助力。教師資格考試為師資生修習師培課程能力認證的門檻，分析試題中的認知層次分布及人工智慧工具（例：ChatGPT）的答題表現，以探索在教學輔助能力的表現有其必要性。本研究選取 2019 年到 2022 年國民小學教師資格考試中的教育專業科目，即「教育理念與實務」、「學習者發展與適性輔導」和「課程教學與評量」三科相關考科的試題，共 560 題，運用修訂後的 Bloom 認知分類六層次，並再區分為高、低層次對不同考科試題及題型進行分析。此外，研究者探查 ChatGPT 於相關考科的總得分，並以盒鬚圖比較 ChatGPT 在不同科目和題型中高、低認知層次試題得分比的分 布情形。結果顯示，教師資格考試的教育專業科目中，三科考科的低認知層次試題占分比都高於高認知層次試題。符應素養導向評量要求的綜合題，高認知層次占分比較高，達81.67 % ，但選擇題的高認知層次占分比僅達6.55 % ，有提升高認知層次比例的必要。此外，ChatGPT 在教育專業科目平均總分為 72.73 分，成功通過教師資格考試平均 60 分的門檻，但對於高認知層次試題的表現歧異度大。這表示 ChatGPT 具有成為師資養成輔助工具的潛力，但教育工作者仍需特別注意高層次認知情境的評鑑與批判。 Training teachers to develop higher cognitive levels to address complex teaching challenges is necessary. Artificial intelligence (e.g., ChatGPT) holds the potential to assist in teacher education. Teacher qualification examination serves as a threshold for certifying pre-service teachers' abilities in pursuing teacher education curricula. Analyzing the distribution of cognitive levels in examination questions and assessing the performance of artificial intelligence tools in answering these questions is necessary to explore their potential in aiding teaching assistance. This study selected 560 education professional examination questions from the elementary school teacher qualification examination between 2019 and 2022. We used the revised Bloom's cognitive taxonomy to analyze and categorize questions into high and low cognitive levels. We investigated the ChatGPT scores in the relevant subject areas and compared the differences in score distribution between high and low cognitive levels across different subjects and question types using box plots. The results indicate that the percentage of low-order questions in all three subjects was higher than that of high-order questions in the teacher qualification examination of education professional subjects. The proportion of high-order comprehensive questions has increased to 81.67 % to meet the competence-oriented assessment requirements. The percentage for multiplechoice questions remains relatively low at only 6.55 %. This indicates a need to increase the proportion of high-order questions. Furthermore, ChatGPT achieved an average total score of 72.73 points in the education professional subjects, surpassing the threshold of an average score of 60 points for the teacher qualification examination. However, there was significant variability in its performance on high-order questions. This suggests that ChatGPT can potentially become an assistive tool for teacher education. However, educators must consider developing critical thinking skills in high-order cognitive contexts when using such tools.

Background/Aims Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P

Objective: We present mosaic distal 9p deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome. Case report: A 34-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(9)(p23)[8]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 43% mosaicism for the 9p24.3p23 deletion. Prenatal ultrasound suspected hypospadias and echogenic bowel. At 23 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(9)(p23)[10]/46,XY[10]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 9 by quantitative fluorescence polymerase chain reaction (QF-PCR) and arr 9p24.3p23 × 1.55 (40%–50% mosaicism) by aCGH. At 27 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 46,XY,del(9)(p23)[6]/46,XY[14]. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 9p24.3p23 (35% mosaicism). Prenatal ultrasound was normal. She was advised to continue the pregnancy, and a 3020-g phenotypically normal male baby was delivered at 41 weeks of gestation. At birth, the karyotypes of cord blood, umbilical cord and placenta were 46,XY,del(9)(p23)[7]/46,XY[37], 46,XY,del(9)(p23)[17]/46,XY[23] and 46,XY in 40/40 cells, respectively. When follow-up at age three months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(9)(p23)[3]/46,XY[37], and interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed 13% (13/102 cells) mosaicism for the distal 9p deletion. Conclusion: Mosaic distal 9p deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.

Abstract Background Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis. Methods Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses. Results The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis. Conclusions Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Abstract Autophagy can be classified as degradative and secretory based on distinct functions. The small GTPase proteins Rab8a and Rab37 are responsible for secretory autophagy‐mediated exocytosis of IL‐1β, insulin, and TIMP1 (tissue inhibitor of 54 metalloproteinase 1). Other Rab family members participating in secretory autophagy are poorly understood. Herein, we identified 26 overlapped Rab proteins in purified autophagosomes of mouse pancreatic β‐cell “Min‐6” and human lung cancer cell “CL1‐5‐Q89L” with high secretory autophagy tendency by LC–MS/MS proteomics analysis. Six Rab proteins (Rab8a, Rab11b, Rab27a, Rab35, Rab37, and Rab7a) were detected in autophagosomes of four cell lines, associating them with autophagy‐related vesicle trafficking. We used CL1‐5‐Q89L cell line model to evaluate the levels of Rab proteins colocalization with autophagy LC3 proteins and presence in purified autophagosomes. We found five Rab proteins (Rab8a, Rab11b, Rab27a, Rab35, and Rab37) are highly expressed in the autophagosome compared to the normal control by immunoblotting under active secretion conditions. However, only Rab8a, Rab35, and Rab37 showing high colocalization with LC3 protein by cofocal microscopy. Despite the discrepancy between the image and immunoblotting analysis, our data sustains the speculation that Rab8a, Rab11b, Rab27a, Rab35, and Rab37 are possibly associated with the secretory autophagy machinery. In contrast, Rab7a shows low colocalization with LC3 puncta and low level in the autophagosome, suggesting it regulates different vesicle trafficking machineries. Our findings open a new direction toward exploring the role of Rab proteins in secretory autophagy‐related cargo exocytosis and identifying the cargoes and effectors regulated by specific Rab proteins.

Abstract Autophagy is a self‐recycling machinery to maintain cellular homeostasis by degrading harmful materials in the cell. Autophagy‐related gene 5 (Atg5) is required for autophagosome maturation. However, the role of Atg5 in tumorigenesis under autophagy deficient conditions remains unclear. This study focused on the autophagy‐independent role of Atg5 and the underlying mechanism in tumorigenesis. We demonstrated that knockout of autophagy‐related genes including Atg5, Atg7, Atg9, and p62 in mouse embryonic fibroblast (MEF) cells consistently decreased cell proliferation and motility, implying that autophagy is required to maintain diverse cellular functions. An Atg7 knockout MEF (Atg7−/− MEF) cell line representing deprivation of autophagy function was used to clarify the role of Atg5 transgene in tumorigenesis. We found that Atg5‐overexpressed Atg7−/‐MEF (clone A) showed increased cell proliferation, colony formation, and migration under autophagy deficient conditions. Accordingly, rescuing the autophagy deficiency of clone A by overexpression of Atg7 gene shifts the role of Atg5 from pro‐tumor to anti‐tumor status, indicating the dual role of Atg5 in tumorigenesis. Notably, the xenograft mouse model showed that clone A of Atg5‐overexpressed Atg7−/− MEF cells induced temporal tumor formation, but could not prolong further tumor growth. Finally, biomechanical analysis disclosed increased Wnt5a secretion and p‐JNK expression along with decreased β‐catenin expression. In summary, Atg5 functions as a tumor suppressor to protect the cell under normal conditions. In contrast, Atg5 shifts to a pro‐tumor status under autophagy deprivation conditions.

This paper gives a full description of development of foreign air-to-air missiles in 2023. It pre-sents the latest advancement progress and testing situation of AIM-9X, AIM-120,AIM-260, LongShot program, Modular Advanced Missile, MUTANT project, ASRAAM, IRIS-T, Meteor missile, innovative missile technologies, and RVV-MD2, JNAAM, Sky Spear, Astra BVRAAM. In the end, this paper summarizes the new development features of air-to-air missiles.

Background: Glove reuse poses risks, as chemicals can persist even after cleaning. Decontamination methods like thermal aeration, recommended by US OSHA, vary in effectiveness. Some studies show promising results, while others emphasize the importance of considering both permeation and tensile strength changes. This research advocates for informed glove reuse, emphasizing optimal thermal aeration temperatures and providing evidence to guide users in maintaining protection efficiency. Methods: The investigation evaluated Neoprene and Nitrile gloves (22 mils). Permeation tests with toluene and acetone adhered to American Society for Testing Materials (ASTM) F739 standards. Decontamination optimization involved aeration at various temperatures. The experiment proceeded with a maximum of 22 re-exposure cycles. Tensile strength and elongation were assessed following ASTM D 412 protocols. Breakthrough time differences were statistically analyzed using t-test and ANOVA. Results: At room temperature, glove residuals decreased, and standardized breakthrough time (SBT)2 was significantly lower than SBT1, indicating reduced protection. Higher temperature decontamination accelerated residual removal, with ΔSBT (SBT2/SBT1) exceeding 100%, signifying restored protection. Tensile tests showed stable neoprene properties postdecontamination. Results underscore thermal aeration's efficacy for gloves reuse, emphasizing temperature's pivotal role. Findings recommend meticulous management strategies, especially post-breakthrough, to uphold glove-protective performance. Conclusions: Thermal aeration at 100°C for 1 hour proves effective, restoring protection without compromising glove strength. The study, covering twenty cycles, suggests safe glove reuse with proper decontamination, reducing costs significantly. However, limitations in chemical-glove combinations and exclusive focus on specific gloves caution against broad generalization. The absence of regulatory directives on glove reuse highlight the importance of informed selection and rigorous decontamination validation for workplace safety practices.

Abstract Background Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype–phenotype correlations of USH2A-related retinal dystrophies in Taiwan. Results In our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference. Conclusions This is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.

Abstract Background Most tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown. Results Here, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition. Conclusions Our study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom’s cell membrane.

Background: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. Methods: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. Results: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P

IntroductionWhen elderly patients have underlying diseases combined with oromaxillofacial diseases requiring surgical treatment, the application of conventional general anesthesia (GA) for oromaxillofacial surgical diseases has become a risk due to underlying disease reasons. The objective of this study was to evaluate the efficacy and safety of ultrasound-guided superficial cervical plexus block (SCPB) anesthesia combined with local infiltration anesthesia (LIA) for partial oral and maxillofacial surgery (OMFS) in patients who with risk for GA due to underlying disease.MethodsThe clinical data of 7 high risk patients with OMFS treated with SCPB anesthesia combined with LIA were retrospectively analyzed. All seven surgeries were performed on one side of the neck. All patients were given ultrasound-guided SCPB anesthesia by the same anesthesiologist, LIA by the same surgeon, and surgery was performed under continuous Electrocardiogram (ECG) monitoring.ResultsSeven patients had stable vital signs and no significant postoperative complications. The results of this study indicated that SCPB anesthesia combined with LIA is a safe and effective anesthesia technique with a high success rate and patient tolerance.DiscussionFor patients with OMFS who have a risk for GA due to underlying diseases, ultrasound-guided cervical superficial plexus block anesthesia combined with LIA is a safe and effective alternative to conventional GA.

Cancer research is continuously exploring new avenues to improve treatments, and ferroptosis induction has emerged as a promising approach. However, the lack of comprehensive analysis of the ferroptosis sensitivity in different cancer types has limited its clinical application. Moreover, identifying the key regulator that influences the ferroptosis sensitivity during cancer progression remains a major challenge. In this study, we shed light on the role of ferroptosis in colorectal cancer and identified a novel ferroptosis repressor, NUDT16L1, that contributes to the ferroptosis insensitivity in this cancer type. Mechanistically, NUDT16L1 promotes ferroptosis insensitivity in colon cancer by enhancing the expression of key ferroptosis repressor and mitochondrial genes through direct binding to NAD-capped RNAs and the indirect action of MALAT1. Our findings also reveal that NUDT16L1 localizes to the mitochondria to maintain its proper function by preventing mitochondrial DNA leakage after treatment of ferroptosis inducer in colon cancer cells. Importantly, our orthotopic injection and Nudt16l1 transgenic mouse models of colon cancer demonstrated the critical role of NUDT16L1 in promoting tumor growth. Moreover, clinical specimens revealed that NUDT16L1 was overexpressed in colorectal cancer, indicating its potential as a therapeutic target. Finally, our study shows the therapeutic potential of a NUDT16L1 inhibitor in vitro, in vivo and ex vivo. Taken together, these findings provide new insights into the crucial role of NUDT16L1 in colorectal cancer and highlight its potential as a promising therapeutic target.

Background Coronavirus disease 2019 (COVID-19) has a considerable impact on the global healthcare system. Individuals who have recovered from COVID often experience chronic respiratory symptoms that affect their daily lives. This study aimed to assess respiratory dynamics such as airway hyperresponsiveness (AHR) and bronchodilator response in post-COVID patients. Methods This study included 282 adults with respiratory symptoms who underwent provocation tests. The demographic details, clinical symptoms and medical histories were recorded. Baseline spirometry, methacholine challenge tests (MCT) and post-bronchodilator spirometry were performed. Patients were divided into the following four groups: Group 1: non-COVID-19 and negative MCT; Group 2: post-COVID-19 and negative MCT; Group 3: non-COVID-19 and positive MCT; and Group 4: post-COVID-19 and positive MCT. Results Most post-COVID-19 patients (43.7%) experienced AHR, and wheezing was more common. Patients in Group 4 exhibited increased intensities of dyspnoea, cough and wheezing with the lowest pulmonary function test (PFT) parameters at baseline. Moreover, significant decreases in PFT parameters after the MCT were observed in these patients. Although the prevalence of a low forced expiratory volume in 1 s to forced vital capacity ratio (

Pseudorabies virus (PRV) is the pathogenic agent of pseudorabies, causing serious reproductive failure in swine. However, it is still unknown whether PRV uterine inoculation impairs blastocyst implantation. In the present study, a PRV infection mouse model was developed. Pregnant mice were inoculated with either 104 or 105 50% tissue culture infectious dose (TCID50) units of PRV on gestation day 2 (GD2). Viral DNA was detected in tissues by PCR and/or in situ hybridization. Histopathological change and expression of proinflammatory cytokines in uterus were analyzed by H.E. staining and qPCR, respectively. Apoptosis was also investigated by TUNEL assay, and the expression of apoptosis-related proteins including Bax and Bcl-2 was detected by Western blot. The results showed that intrauterine exposure of PRV on GD2 reduced the number of embryo implantation site. Abundant viral DNA was detected in spinal marrow and brain, and small amounts of PRV genomes were detected in embryo implantation site, ovary as well as thymus. Considerable inflammatory cells infiltrating in the endometrium, with high levels of pro-inflammatory cytokines of interleukin (IL)-6, IL-1β and tumor necrosis factor-α mRNA after infection. In addition, PRV infection promoted apoptosis in stroma and endothelium of the mouse endometrium. Collectively, intrauterine inoculation of PRV during early pregnancy causes cytokine release syndrome and apoptosis in endometrium, which impairs mouse embryo implantation.

Glioma is a common primary malignant brain tumor with low survival rate. Immunotherapy with immune checkpoints inhibitors (ICI) can be a choice for glioma management, and extracellular vesicles (EVs) are recognized as a potential drug delivery system for various disease management due to their enhanced barrier permeation ability and immunomodulatory effect. The aim of this study is to develop ICI-loaded EVs (ICI/EV) that have sufficient efficacy in managing glioma. Calcium phosphate particles (CaP) were used to stimulate the secretion of EVs from murine macrophage cells. CaP conditioning of cells showed an enhanced amount of EVs secretion and macrophage polarization toward a proinflammatory phenotype. The CaP-induced EVs were shown to polarize macrophages into proinflammatory phenotype in vitro, as correlated with the conditioning method. ICI/EVs were successfully prepared with high loading efficiency using the sonication method. The EVs can be distributed throughout the entire brain upon intranasal administration and facilitate ICIs distribution into glioma lesion. Combinatory treatment with ICI/EVs showed benefit in glioma-bearing mice by reducing their tumor volume and prolonging their survival. Cytotoxic T cell infiltration, polarization of tumor-associated macrophage, and lower tumor proliferation were observed in ICI/EVs-treated mice. The developed ICI/EVs showed promise in immunotherapeutic management of glioma.

The tumor immune microenvironment (TIME) significantly influences cancer progression and treatment. This study sought to uncover novel TIME-related glioma biomarkers to advance antitumor immunotherapies by integrating data from sequencing of bulk RNA as well as scRNA. Immunologic and epithelial-mesenchymal transition (EMT) characteristics were used to classify glioma patients into two immune subtypes (ISs) and two EMT subtypes (ESs). Patients in IS1 and ES1, characterized by high immune infiltration and low stemness scores, exhibited poor clinical outcomes and limited responsiveness to immunotherapy. A new risk signature was developed using 16 genes and validated in independent glioma cohorts. Among these, HAVCR2, IL18, LAGLS9, and PTPN6 emerged as hub genes, with IL18 identified as a potential independent indicator. The upregulation of IL18 in high-grade gliomas and U-251 MG cells aligned with bioinformatics analysis. These insights deepen the understanding of TIME-related mechanisms in glioma and highlight potential therapeutic targets, offering a theoretical foundation for effective antitumor immunotherapies in glioma.

Background: While hyperuricemia has been correlated with cardiovascular (CV) diseases, further evidence is required to evaluate the implications of stable serum uric acid (sUA) levels, especially concerning low sUA. This study aimed to investigate prolonged stable sUA levels and CV events/mortality. Methods: We conducted a retrospective cohort study at a medical center using electronic medical records linked with the national claims database. Patients with at least two sUA measurements, with intervals ranging from 6 months to 4 years, were included. The mean of the first two eligible sUA measurements were analyzed, stratified by sex. Outcomes of interest comprised major adverse cardiovascular events (MACE), heart failure hospitalization, CV and all-cause mortality. Results: This study included 33,096 patients (follow-up: men 6.6 years, women 6.4 years). After multivariable adjustment, cubic spline models showed that long-term high sUA levels were consistently associated with a higher risk of MACE, heart failure hospitalization, CV and all-cause mortality. A U-shaped association was observed between sUA levels and all-cause mortality in both sexes and between sUA levels and CV mortality in women. The impact of sUA, especially lower levels, on CV events and mortality was more pronounced in women than in men. Conclusion: Long-term high sUA levels are consistently associated with increased risk of CV events and mortality. A U-shaped association between sUA levels and all-cause mortality was observed in both men and women and was pronounced in women. The findings underscore the importance of considering sUA levels, especially in women, when assessing CV risk.

Abstract Background Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood. Methods This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period. Results We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p

Objective: We present mosaic distal 10q deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome. Case report: A 40-year-old, gravida 2, para 0, woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(10) (q26.13)[6]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 35% mosaicism for the 10q26.13q26.3 deletion. At 22 weeks of gestation, she underwent cordocentesis which revealed a karyotype of 46,XY,del(10) (q26.13)[16]/46,XY[24]. Prenatal ultrasound findings were normal. At 24 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(10) (q26.13)[4]/46,XY[22]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 10 by quantitative fluorescence polymerase chain reaction (QF-PCR), arr 10q26.13q26.3 × 1.6 (40% mosaicism) by aCGH, and 29.8% (31/104 cells) mosaicism for the distal 10q deletion by interphase fluorescence in situ hybridization (FISH). The woman was advised to continue the pregnancy, and a phenotypically normal 2,900-g male baby was delivered at 39 weeks of gestation. The cord blood had a karyotype of 46,XY,del(10) (q26.13)[6]/46,XY[34], and both the umbilical cord and the placenta had the karyotype of 46,XY. When follow-up at age four months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(10) (q26.13)[5]/46,XY[35], and interphase FISH analysis on buccal mucosal cells showed 8% (8/102 cells) mosaicism for distal 10q deletion. Conclusion: Mosaic distal 10q deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.