Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study.

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

RanGAP1 maintains chromosome stability in limb bud mesenchymal cells during bone development.

BACKGROUND: Bone development involves the rapid proliferation and differentiation of osteogenic lineage cells, which makes accurate chromosomal segregation crucial for ensuring cell proliferation and maintaining chromosomal stability. However, the mechanism underlying the maintenance of chromosome stability during the rapid proliferation and differentiation of Prx1-expressing limb bud mesenchymal cells into osteoblastic precursor cells remains unexplored. METHODS: A transgenic mouse model of RanGAP1 knockout of limb and head mesenchymal progenitor cells was constructed to explore the impact of RanGAP1 deletion on bone development by histomorphology and immunostaining. Subsequently, G-banding karyotyping analysis and immunofluorescence staining were used to examine the effects of RanGAP1 deficiency on chromosome instability. Finally, the effects of RanGAP1 deficiency on chromothripsis and bone development signaling pathways were elucidated by whole-genome sequencing, RNA-sequencing, and qPCR. RESULTS: The ablation of RanGAP1 in limb and head mesenchymal progenitor cells expressing Prx1 in mice resulted in embryonic lethality, severe cartilage and bone dysplasia, and complete loss of cranial vault formation. Moreover, RanGAP1 loss inhibited chondrogenic or osteogenic differentiation of mesenchymal stem cells (MSCs). Most importantly, we found that RanGAP1 loss in limb bud mesenchymal cells triggered missegregation of chromosomes, resulting in chromothripsis of chromosomes 1q and 14q, further inhibiting the expression of key genes involved in multiple bone development signaling pathways such as WNT, Hedgehog, TGF-ß/BMP, and PI3K/AKT in the chromothripsis regions, ultimately disrupting skeletal development. CONCLUSIONS: Our results establish RanGAP1 as a critical regulator of bone development, as it supports this process by preserving chromosome stability in Prx1-expressing limb bud mesenchymal cells.

Integrated metabolomics analysis reveals mechanistic insights into variability in blood pressure response to thiazide diuretics and beta blockers.

Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to ß-blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). TDs and BBs are suggested to reduce BP in the long term through vasodilation via incompletely understood mechanisms. This study aimed at identifying pathways underlying ancestral differences in PRA, which might reflect pathways underlying BP-lowering mechanisms of TDs and BBs. Among hypertensive participants enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, we previously identified 8 metabolites associated with baseline PRA and 4 metabolic clusters (including 39 metabolites) that are different between those with GWAA <45% versus ≥45%. In the current study, using Ingenuity Pathway Analysis (IPA), we integrated these signals. Three overlapping metabolic signals within three significantly enriched pathways were identified as associated with both PRA and %GWAA: ceramide signaling, sphingosine 1- phosphate signaling, and endothelial nitric oxide synthase signaling. Literature indicates that the identified pathways are involved in the regulation of the Rho kinase cascade, production of the vasoactive agents nitric oxide, prostacyclin, thromboxane A2, and endothelin 1; the pathways proposed to underlie TD- and BB-induced vasodilatation. These findings may improve our understanding of the BP-lowering mechanisms of TDs and BBs. This might provide a possible step forward in personalizing antihypertensive therapy by identifying patients expected to have robust BP-lowering effects from these drugs.

Mecp2 fine-tunes quiescence exit by targeting nuclear receptors.

Quiescence (G0) maintenance and exit are crucial for tissue homeostasis and regeneration in mammals. Here, we show that methyl-CpG binding protein 2 (Mecp2) expression is cell cycle-dependent and negatively regulates quiescence exit in cultured cells and in an injury-induced liver regeneration mouse model. Specifically, acute reduction of Mecp2 is required for efficient quiescence exit as deletion of Mecp2 accelerates, while overexpression of Mecp2 delays quiescence exit, and forced expression of Mecp2 after Mecp2 conditional knockout rescues cell cycle reentry. The E3 ligase Nedd4 mediates the ubiquitination and degradation of Mecp2, and thus facilitates quiescence exit. A genome-wide study uncovered the dual role of Mecp2 in preventing quiescence exit by transcriptionally activating metabolic genes while repressing proliferation-associated genes. Particularly disruption of two nuclear receptors, Rara or Nr1h3, accelerates quiescence exit, mimicking the Mecp2 depletion phenotype. Our studies unravel a previously unrecognized role for Mecp2 as an essential regulator of quiescence exit and tissue regeneration.

Liver-specific mitochondrial amidoxime-reducing component 1 (Mtarc1) knockdown protects the liver from diet-induced MASH in multiple mouse models.

BACKGROUND: Human genetic studies have identified several mitochondrial amidoxime-reducing component 1 (MTARC1) variants as protective against metabolic dysfunction-associated steatotic liver disease. The MTARC1 variants are associated with decreased plasma lipids and liver enzymes and reduced liver-related mortality. However, the role of mARC1 in fatty liver disease is still unclear. METHODS: Given that mARC1 is mainly expressed in hepatocytes, we developed an N-acetylgalactosamine-conjugated mouse Mtarc1 siRNA, applying it in multiple in vivo models to investigate the role of mARC1 using multiomic techniques. RESULTS: In ob/ob mice, knockdown of Mtarc1 in mouse hepatocytes resulted in decreased serum liver enzymes, LDL-cholesterol, and liver triglycerides. Reduction of mARC1 also reduced liver weight, improved lipid profiles, and attenuated liver pathological changes in 2 diet-induced metabolic dysfunction-associated steatohepatitis mouse models. A comprehensive analysis of mARC1-deficient liver from a metabolic dysfunction-associated steatohepatitis mouse model by metabolomics, proteomics, and lipidomics showed that Mtarc1 knockdown partially restored metabolites and lipids altered by diet. CONCLUSIONS: Taken together, reducing mARC1 expression in hepatocytes protects against metabolic dysfunction-associated steatohepatitis in multiple murine models, suggesting a potential therapeutic approach for this chronic liver disease.

Effectiveness of Clopidogrel vs Alternative P2Y12 Inhibitors Based on the ABCD-GENE Score.

BACKGROUND: An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear. OBJECTIVES: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y12 inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI). METHODS: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y12 inhibitor treatment were included. The primary outcome was major atherothrombotic events (MAE) within 1 year after PCI. Cox regression was performed to assess event risk in clopidogrel-treated (reference) vs alternatively treated patients, with stabilized inverse probability weights derived from exposure propensity scores after stratifying by ABCD-GENE score and further by CYP2C19 loss-of-function (LOF) genotype. RESULTS: Among patients with scores <10 (n = 3,200), MAE was not different with alternative therapy vs clopidogrel (weighted HR: 0.89; 95% CI: 0.65-1.22; P = 0.475). The risk for MAE also did not significantly differ by treatment among patients with scores ≥10 (n = 1,135; weighted HR: 0.75; 95% CI: 0.51-1.11; P = 0.155). Among CYP2C19 LOF allele carriers, MAE risk appeared lower with alternative therapy in both the group with scores <10 (weighted HR: 0.50; 95% CI: 0.25-1.01; P = 0.052) and the group with scores ≥10 (weighted HR: 0.48; 95% CI: 0.29-0.80; P = 0.004), while there was no difference in the group with scores <10 and no LOF alleles (weighted HR: 1.03; 95% CI: 0.70-1.51; P = 0.885). CONCLUSIONS: These data support the use of alternative therapy over clopidogrel in CYP2C19 LOF allele carriers after PCI, regardless of ABCD-GENE score, while clopidogrel is as effective as alternative therapy in non-LOF patients with scores <10.

Assessing the clinical diagnostic value of anti-Müllerian hormone in polycystic ovarian syndrome and its correlation with clinical and metabolism indicators.

BACKGROUND: This study investigated the association between Anti-Müllerian Hormone (AMH) and relevant metabolic parameters and assessed its predictive value in the clinical diagnosis of polycystic ovarian syndrome (PCOS). METHODS: A total of 421 women aged 20-37 years were allocated to the PCOS (n = 168) and control (n = 253) groups, and their metabolic and hormonal parameters were compared. Spearman correlation analysis was conducted to investigate associations, binary logistic regression was used to determine PCOS risk factors, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of AMH in diagnosing PCOS. RESULTS: The PCOS group demonstrated significantly higher blood lipid, luteinizing hormone (LH), and AMH levels than the control group. Glucose and lipid metabolism and hormonal disorders in the PCOS group were more significant than in the control group among individuals with and without obesity. LH, TSTO, and AMH were identified as independent risk factors for PCOS. AMH along with LH, and antral follicle count demonstrated a high predictive value for diagnosing PCOS. CONCLUSION: AMH exhibited robust diagnostic use for identifying PCOS and could be considered a marker for screening PCOS to improve PCOS diagnostic accuracy. Attention should be paid to the effect of glucose and lipid metabolism on the hormonal and related parameters of PCOS populations.

Flexible high-density microelectrode arrays for closed-loop brain-machine interfaces: a review.

Flexible high-density microelectrode arrays (HDMEAs) are emerging as a key component in closed-loop brain-machine interfaces (BMIs), providing high-resolution functionality for recording, stimulation, or both. The flexibility of these arrays provides advantages over rigid ones, such as reduced mismatch between interface and tissue, resilience to micromotion, and sustained long-term performance. This review summarizes the recent developments and applications of flexible HDMEAs in closed-loop BMI systems. It delves into the various challenges encountered in the development of ideal flexible HDMEAs for closed-loop BMI systems and highlights the latest methodologies and breakthroughs to address these challenges. These insights could be instrumental in guiding the creation of future generations of flexible HDMEAs, specifically tailored for use in closed-loop BMIs. The review thoroughly explores both the current state and prospects of these advanced arrays, emphasizing their potential in enhancing BMI technology.

Growth of diamond in liquid metal at 1 atm pressure.

Natural diamonds were (and are) formed (thousands of million years ago) in the upper mantle of Earth in metallic melts at temperatures of 900-1,400 °C and at pressures of 5-6 GPa (refs. 1,2). Diamond is thermodynamically stable under high-pressure and high-temperature conditions as per the phase diagram of carbon3. Scientists at General Electric invented and used a high-pressure and high-temperature apparatus in 1955 to synthesize diamonds by using molten iron sulfide at about 7 GPa and 1,600 °C (refs. 4-6). There is an existing model that diamond can be grown using liquid metals only at both high pressure and high temperature7. Here we describe the growth of diamond crystals and polycrystalline diamond films with no seed particles using liquid metal but at 1 atm pressure and at 1,025 °C, breaking this pattern. Diamond grew in the subsurface of liquid metal composed of gallium, iron, nickel and silicon, by catalytic activation of methane and diffusion of carbon atoms into and within the subsurface regions. We found that the supersaturation of carbon in the liquid metal subsurface leads to the nucleation and growth of diamonds, with Si playing an important part in stabilizing tetravalently bonded carbon clusters that play a part in nucleation. Growth of (metastable) diamond in liquid metal at moderate temperature and 1 atm pressure opens many possibilities for further basic science studies and for the scaling of this type of growth.

Clinical features and risk factors of primary Sjögren's syndrome complicated with severe pneumonia: a case-control study.

OBJECTIVES: To analyze clinical characteristics, risk factors, pathogen distribution, and prognostic markers in primary Sjögren's syndrome (pSS) patients with severe pneumonia (SP) compared to those without severe pneumonia (NSP). METHODS: This case-control study included 24 hospitalized pSS patients with SP and 96 NSP at the first affiliated hospital of Soochow university from June 2014 to May 2023. Data encompassing demographics, comorbidities, treatments, and laboratory results were retrospectively collected. Univariate and multivariate regression analyses, ROC curves, and statistical analyses using SPSS 23.0 assessed risk factors. The study retrospectively analyzed clinical features and risk factors, highlighting distinct parameters between pSS patients with and without SP. RESULTS: Marked differences were observed in several parameters: pSS activity(P < 0.001), white blood cell (P = 0.043), lymphocyte (P < 0.001), neutrophils (P = 0.042), C-reactive protein (P = 0.042), and CD8+ T cell (P = 0.017). Notably, lymphocyte count and SS activity demonstrated robust discrimination ability (AUC > 0.85). C-reactive protein (CRP), procalcitonin, CD4+ T cell, and IgA showed significant associations with SP; higher CRP levels correlated with increased risk, while lower CD4+ T cell and IgA levels associated with increased risk. SS activity significantly impacted outcomes. Various biomarkers exhibited diverse discriminatory abilities but lacked strong predictive associations with outcomes. CONCLUSION: pSS patients with SP exhibited higher disease activity and altered immune profiles compared to those NSP. Lymphocyte count and SS activity emerged as robust discriminators. Higher CRP levels correlated with increased risk of SP, while lower CD4+T cell and IgA levels associated with increased risk. SS activity significantly impacted patient outcomes. Key Points • pSS patients with SP exhibited higher disease activity and altered immune profiles compared to those NSP. • Lymphocyte count and SS activity emerged as robust discriminators. • Higher CRP levels correlated with increased risk of SP, while lower CD4+ T cell and IgA levels associated with decreased risk. • SS activity significantly impacted patient outcomes.

Knowledge, attitude, and practice toward weight management among diabetic patients in Qidong City, Jiangsu Province.

BACKGROUND: Weight management is an effective prevention and treatment strategy for diabetes mellitus. This study aimed to assess the knowledge, attitude, and practice (KAP) of diabetic patients towards weight management. METHODS: Diabetic patients treated at Qidong City, Jiangsu Province, between January 2023 and June 2023 were included in this cross-sectional study. A self-designed questionnaire was used to collect their demographic characteristics and KAP toward weight management. Structural equation modeling (SEM) was employed to examine the inter-relationships among KAP scores. RESULTS: Among a total of 503 valid questionnaires that were collected, 55.07% were filled out by men and 54.67% by those aged < 60 years. The mean scores for knowledge, attitude, and practice were 8.03 ± 3.525 (possible range: 0-13), 31.88 ± 3.524 (possible range: 10-50), and 22.24 ± 3.318 (possible range: 9-45), respectively. Pearson's correlation analysis revealed the knowledge was positively associated with attitude (r = 0.295, P < 0.001) and practice (r = 0.131, P < 0.001), and attitude was positively associated with practice (r = 0.140, P = 0.002). SEM demonstrated positive associations between knowledge and attitude (ß = 0.28, P < 0.001), and attitude and practice (ß = 0.09, P = 0.019). Moreover, older age was negatively associated with knowledge (ß=-0.04, P = 0.001), while higher education (ß = 1.220, P < 0.001), increased monthly income (ß = 0.779, P < 0.001), diagnosis of fatty liver (ß = 1.03, P = 0.002), and screening for excess visceral fat (ß = 1.11, P = 0.002) were positively associated with knowledge. CONCLUSION: Diabetic patients showed moderate knowledge, neutral attitudes, and inappropriate practices toward weight management. Knowledge was positively associated with attitude and practice. These findings provided valuable directions for healthcare interventions targeting improved KAP status of weight management among diabetic patients.

Benefit finding in individuals undergoing maintenance hemodialysis in Shanghai: a latent profile analysis.

Objective: This multi-center cross-sectional study aimed to delineate latent profiles of benefit finding (BF) in individuals undergoing maintenance hemodialysis (MHD) in Shanghai and examine associations between these BF profiles, social support, and coping style. Methods: A total of 384 individuals undergoing MHD (mean age = 57.90, SD = 13.36) were assessed using the Benefit Finding Scale, Simplified Coping Style Questionnaire, and Perceived Social Support Scale. Latent profile analysis (LPA) identified distinct BF categories. Analysis of variance (ANOVA) evaluated the correlation between BF groups and demographic variables, while the relationship between BF, social support, and coping style was tested through correlation and multiple regression analyses. Results: LPA identified three BF groups: rich BF (54.17%), moderate BF (41.14%), and poor BF (4.69%). Regression analyses indicated that positive coping and social support are protective factors for BF. Additionally, older age and heightened understanding of MHD correlated with higher BF levels. Conclusion: The findings highlighted the importance of recognizing different BF profiles in individuals on MHD and working toward promoting BF levels in the rich BF and moderate BF groups, while helping the poor BF group to identify and address their challenges. Medical professionals should consider interventions tailored to individual psychological profiles to improve mental health and quality of life outcomes in this population.

Haglund resection versus Haglund non-resection for calcific insertional Achilles tendinopathy with Haglund deformity: A retrospective study.

BACKGROUND: Calcific insertional Achilles tendinopathy(CIAT) with Haglund deformity is a type of recalcitrant tendinopathy. The necessity of concomitant removal of Haglund deformity during CIAT treatment is controversial. The present study aimed to evaluate the functional outcomes between Haglund resection and Haglund non-resection in the treatment of CIAT with Haglund deformity. METHODS: A retrospective study included 29 patients who were underwent Achilles tendon debridement, bursal excision, and subsequent tendon reattachment.for CIAT with Haglund deformity. All patients were divided into 2 groups according to Haglund resection (resection group, n = 16) and Haglund non-resection (non-resection group, n = 13) using the parallel line method on lateral calcaneal X ray after surgery. Patients were evaluated in terms of the American Orthopedic Foot and Ankle Society (AOFAS), Visual Analog Scale (VAS) and Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and the mean time of activities of daily living (ADL). Anatomy changes included the Fowler-Philip angle, calcaneal pitch angle and Achilles tendon force arm were measured with radiography preoperatively and postoperatively. RESULTS: Both groups exhibited a significant increase in AOFAS, VAS and VISA-A scores after surgery. There were no significant differences between the resection group and the non-resection group for the AOFAS (92.38 ± 5.7 vs. 93.15 ± 12.17; P = 0.82), VAS (0.5 ± 0.52 vs. 0.61 ± 0.87; P = 0.66) and VISA-A questionnaire (82.56 ± 13.46 vs. 74.92 ± 16.4; P = 0.18) at the latest follow-up. The mean time of ADL in the non-resection group was significantly faster compared to that of the resection group (8.15 ± 2.51 weeks vs. 11.31 ± 4.06 weeks, P = 0.02). The Fowler-Philip angle of the resection group decreased from 55.55° ± 12.34° preoperatively to 44.52° ± 10.24° at the latest follow-up (P = 0.001). The Fowler-Philip angle of the non-resection group decreased from 54.38° ± 8.41° preoperatively to 46.52° ± 8.02° at the latest follow-up (P = 0.016). The calcaneal pitch angle of the resection group increased from 22.76° ± 5.37° preoperatively to 25.98° ± 6. 4° at the latest follow-up (P = 0.018). The Achilles tendon force arm of the resection group decreased from 178.50 mm ± 5.37 mm preoperatively to 173.90 mm ± 8.07 mm at the latest follow-up (P = 0.018). CONCLUSION: Resection or non-resection of the posterosuperior calcaneal tuberosity for CIAT with Haglund deformity would both provide satisfactory functional outcomes. Haglund non-resection may expedite patients' return to their daily activities, suggesting a Haglund deformity resection may be unnecessary in the surgical treatment for CIAT with Haglund deformity.

Implementation and Challenge of Supported Employment for People With Disabilities in China.

The Chinese government initiated a pilot program to implement supported employment for people with disabilities in 2014. Since then, policies have been enacted to promote supported employment. This study explored how practitioners understand and implement supported employment for people with disabilities in China. It was found that non-governmental service organizations have mainly implemented supported employment with financial support provided by local disabled persons' federations; without a governmental guide, the small-scale folk practice presented many difficulties and unstable factors. Results indicated that the Chinese government should actively establish and improve the supported employment system and further expand supported employment practices at the governmental level.

Large-scale array for radio astronomy on the farside (LARAF).

At the Royal Society meeting in 2023, we have mainly presented our lunar orbit array concept called DSL, and also briefly introduced a concept of a lunar surface array, LARAF. As the DSL concept had been presented before, in this article, we introduce the LARAF. We propose to build an array in the far side of the Moon, with a master station which handles the data collection and processing, and 20 stations with maximum baseline of 10 km. Each station consists of 12 membrane antenna units, and the stations are connected to the master station by power line and optical fibre. The array will make interferometric observation in the 0.1-50 MHz band during the lunar night, powered by regenerated fuel cells. The whole array can be carried to the lunar surface with a heavy rocket mission, and deployed with a rover in eight months. Such an array would be an important step in the long-term development of lunar-based ultralong wavelength radio astronomy. It has a sufficiently high sensitivity to observe many radio sources in the sky, though still short of the dark age fluctuations. We discuss the possible options in the power supply, data communication, deployment etc. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

Molecular classification reveals the sensitivity of lung adenocarcinoma to radiotherapy and immunotherapy: multi-omics clustering based on similarity network fusion.

BACKGROUND: Due to individual differences in tumors and immune systems, the response rate to immunotherapy is low in lung adenocarcinoma (LUAD) patients. Combinations with other therapeutic strategies improve the efficacy of immunotherapy in LUAD patients. Although radioimmunotherapy has been demonstrated to effectively suppress tumors, the underlying mechanisms still need to be investigated. METHODS: Total RNA from LUAD cells was sequenced before and after radiotherapy to identify differentially expressed radiation-associated genes. The similarity network fusion (SNF) algorithm was applied for molecular classification based on radiation-related genes, immune-related genes, methylation data, and somatic mutation data. The changes in gene expression, prognosis, immune cell infiltration, radiosensitivity, chemosensitivity, and sensitivity to immunotherapy were assessed for each subtype. RESULTS: We used the SNF algorithm and multi-omics data to divide TCGA-LUAD patients into three subtypes. Patients with the CS3 subtype had the best prognosis, while those with the CS1 and CS2 subtypes had poorer prognoses. Among the strains tested, CS2 exhibited the most elevated immune cell infiltration and expression of immune checkpoint genes, while CS1 exhibited the least. Patients in the CS2 subgroup were more likely to respond to PD-1 immunotherapy. The CS2 patients were most sensitive to docetaxel and cisplatin, while the CS1 patients were most sensitive to paclitaxel. Experimental validation of signature genes in the CS2 subtype showed that inhibiting the expression of RHCG and TRPA1 could enhance the sensitivity of lung cancer cells to radiation. CONCLUSIONS: In summary, this study identified a risk classifier based on multi-omics data that can guide treatment selection for LUAD patients.

A Fusion of Taq DNA Polymerase with the CL7 Protein from Escherichia coli Remarkably Improves DNA Amplification.

DNA polymerases are important enzymes that synthesize DNA molecules and therefore are critical to various scientific fields as essential components of in vitro DNA synthesis reactions, including PCR. Modern diagnostics, molecular biology, and genetic engineering require DNA polymerases with improved performance. This study aimed to obtain and characterize a new CL7-Taq fusion DNA polymerase, in which the DNA coding sequence of Taq DNA polymerase was fused with that of CL7, a variant of CE7 (Colicin E7 DNase) from Escherichia coli. The resulting novel recombinant open reading frame was cloned and expressed in E. coli. The recombinant CL7-Taq protein exhibited excellent thermostability, extension rate, sensitivity, and resistance to PCR inhibitors. Our results showed that the sensitivity of CL7-Taq DNA polymerase was 100-fold higher than that of wild-type Taq, which required a template concentration of at least 1.8 × 105 nM. Moreover, the extension rate of CL7-Taq was 4 kb/min, which remarkably exceeded the rate of Taq DNA polymerase (2 kb/min). Furthermore, the CL7 fusion protein showed increased resistance to inhibitors of DNA amplification, including lactoferrin, heparin, and blood. Single-cope human genomic targets were readily available from whole blood, and pretreatment to purify the template DNA was not required. Thus, this is a novel enzyme that improved the properties of Taq DNA polymerase, and thus may have wide application in molecular biology and diagnostics.

Reverse dorsolateral proximal phalangeal island flap: Long-term results.

OBJECTIVES: This study aims to present long-term follow-up results of the reverse dorsolateral proximal phalangeal island flap designed for reconstruction of large fingertip and pulp defects. METHODS: We examined 18 patients who underwent reverse dorsolateral proximal phalangeal island flap surgery to address ≥2.5 cm fingertip and pulp defects. Mean follow-up was 84.4 months. Sensitivity assessments were conducted using the Semmes-Weinstein monofilament and 2-point discrimination tests. Additionally, we evaluated finger joint active range of motion, complications and cold intolerance. RESULTS: Mild venous congestion was observed in 5 flaps. Significant differences were observed in 2-point discrimination and Semmes-Weinstein monofilament tests between the injured and contralateral sides, specifically in the flaps, the dorsal side of the middle phalanx, and the donor site. The flap's mean static 2-point discrimination was 8.3 mm. Restricted distal interphalangeal joint extension was observed in 2 cases. Total active motion with the flap was good or excellent in the injured fingers, but with a significant difference between injured and contralateral fingers. Additionally, 42% of the injured fingers exhibited hook nail deformity, and 2 patients reported cold intolerance. Despite these issues, most patients has high scores for the appearance and satisfaction aspects of the Michigan Hand Outcomes Questionnaire. CONCLUSION: In moderate or larger fingertip defects, the reverse dorsolateral proximal phalangeal island flap serves as an alternative for reconstructing both fingertip and pulp issues. However, this option involves sacrificing some sensation in the dorsum of the middle phalangeal finger and the donor area. LEVEL OF EVIDENCE: IV, therapeutic study.