Characterization of the immune cell infiltration landscape in lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have played an important role in the treatment of lung adenocarcinoma (LUAD). However, their effectiveness is limited, and many patients exhibit a weak response. In this study, we propose a new and more effective immunophenotyping method for evaluating the prognosis and tumor microenvironment (TME) cellular infiltration characteristics in LUAD patients and their response to immunotherapy. Based on the transcriptomic and prognostic data of 584 patients with LUAD collected from TCGA cohort and GEO dataset, we combined tumor immune infiltration, the TME, and immune-related genes to score each sample using principal component analysis (PCA) and divided the patients into two subgroups with high and low tumor immune infiltration (TII) scores. The high-TII score group was characterized by increased immune activation and apoptosis signaling pathways. Moreover, clinical subgroup analysis demonstrated that the TII immune score was also applicable to different clinical groups and the high-TII score group still exhibited good prognosis and better response to ICIs. This study mapped the TII landscape in LUAD patients and confirmed that the TII score is helpful for predicting patient response to immunotherapy and may guide more effective immunotherapeutic strategies.

Appropriate Source Control and Antifungal Therapy are Associated with Improved Survival in Critically Ill Surgical Patients with Intra-abdominal Candidiasis.

BACKGROUND: Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in surgical intensive care patients. The purpose of this study was to investigate the impact of appropriate source control and antifungal therapy on the outcomes of critically ill surgical patients with IAC. METHODS: This was a retrospective single-center cohort study. Adult surgical patients who were admitted to the intensive care unit and diagnosed with IAC from January 1, 2003, to December 31, 2016, were enrolled. The patients' data including risk factors of IAC, infection-related information, antifungal treatment and 30-day outcomes were collected. The primary endpoint was 30-day mortality. A COX proportional hazards model was used to analyze the association between appropriate treatment and 30-day survival. RESULTS: A total of 82 patients were included in the analysis. Of these, 45 (54.9%) were complicated with septic shock at IAC diagnosis. Types of IAC included peritonitis (61.0%), intra-abdominal abscesses (23.2%) and biliary tract infections (15.9%). Of the included patients, 53 (64.6%) received appropriate source control and 44 (53.7%) appropriate antifungal therapy. Compared with patients with neither of these treatments, appropriate source control (HR 0.08, 95% CI 0.02-0.30; P < 0.001), appropriate antifungal therapy (HR 0.14, 95% CI 0.04-0.55; P = 0.005), and a combination of these treatments (HR 0.02, 95% CI 0.00-0.08; P < 0.001) were associated with reduced risk of death within 30 days after IAC diagnosis. CONCLUSION: For critically ill surgical patients with IAC, both appropriate source control and appropriate antifungal therapy were associated with reduced risk of 30-day mortality, and the protective effects of the two appropriate treatments were additive.

Overexpression of LncRNA GHET1 predicts an unfavourable survival and clinical parameters of patients in various cancers.

Recently, increasing studies have reported that long non-coding RNA (lncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) is highly expressed in variety of cancers and relevant to poor prognosis of cancer patients. Nevertheless, the results were inconsistent and the systematic analysis of lncRNA GHET1 in cancers has not been inspected. Thus, we aim to evaluate the relationship between lncRNA GHET1 expression and clinical outcomes in human cancers. We searched keywords in PubMed, Web of Science, Embase, Cochrane Library and ClinicalTrial.gov. Stata SE12.0 software was used in the quantitative meta-analysis. Pooled hazard ratio (HR) and odds ratio with 95% confidence interval (95% Cl) were calculated to evaluate the clinical significance of lncRNA GHET1. Twelve studies totalling 761 patients with cancers were included for analysis. The pooled results of this study indicated that high lncRNA GHET1 expression level was significantly associated with poor overall survival (OS, HR = 2.30, 95% CI: 1.75-3.02) in human cancers. The statistical significance was also detected in subgroup analysis stratified by analysis method, cancer type, sample size and follow-up time respectively. In addition, the elevated lncRNA GHET1 expression was also significantly related to more advanced clinical stage, earlier lymph node metastasis, earlier distant metastasis and bigger tumour size. LncRNA GHET1 may serve as a promising biomarker for prognosis in Asians with cancers.

An Active Self-Driven Piezoelectric Sensor Enabling Real-Time Respiration Monitoring.

In this work, we report an active respiration monitoring sensor based on a piezoelectric-transducer-gated thin-film transistor (PTGTFT) aiming to measure respiration-induced dynamic force in real time with high sensitivity and robustness. It differs from passive piezoelectric sensors in that the piezoelectric transducer signal is rectified and amplified by the PTGTFT. Thus, a detailed and easy-to-analyze respiration rhythm waveform can be collected with a sufficient time resolution. The respiration rate, three phases of respiration cycle, as well as phase patterns can be further extracted for prognosis and caution of potential apnea and other respiratory abnormalities, making the PTGTFT a great promise for application in long-term real-time respiration monitoring.

Upregulation of vesicle-associated membrane protein 7 in breast cancer tissues.

BACKGROUND: Vesicle-associated membrane protein 7 (VAMP7) plays oncogenic roles in cancers. However, its clinical significance in breast cancer (BC) tissues remains unknown. OBJECTIVE: To elucidate the clinical implications of VAMP7, as well as its involvement in the tumor microenvironment and molecular pathways of breast cancer. METHODS: BC (n=100) and non-cancerous breast tissues (n= 100) were collected for an immunohistochemical experiment (1:200). The protein expression level of VAMP7 was determined by using a semi-quantitative scoring method. High-throughput RNA-sequencing data of BC tissues were analyzed to confirm the mRNA expression trend of VAMP7. Additionally, the largest BC prognosis cohort data were collected to mine the potential impact VAMP7 has on BC progression. The association between VAMP7 and the microenvironment of BC was evaluated by using a CIBERSORT algorithm. Moreover, we explored the co-expressed molecular mechanisms of VAMP7 in BC by calculating Pearson correlation coefficients and overexpressed genes. Finally, the biological mechanism underlying the relationship between VAMP7 and the key pathways was also explored using gene set enrichment analysis (GSEA). Potential therapeutic strategies were predicted targeting VAMP7. RESULTS: VAMP7 protein was significantly over-expressed in BC tissue than that in controls (p< 0.001). Compared with 459 normal breast tissues and 113 non-cancerous breast tissues, the expression level of VAMP7 mRNA was significantly increased in 1111 BC tissues. CD4+T cells, macrophages, and naïve B cells had a higher infiltration rate in BC tissues with high VAMP7 expression, while regulatory T cells and CD8+T cells had a lower infiltration rate. Over-expressed VAMP7 was associated with macrophages activation and transition from M1 to M2 polarization. Upregulated VAMP7 could predicted poorer OS, DMFS, PPS, and RFS outcomes. Upregulated VAMP7 co-expressed genes were significantly enriched in the cell cycle checkpoints. GSEA confirmed that over-expressed VAMP7 are markedly associated with functional enrichment in cell cycle related categories, including mitotic spindle, G2M checkpoint, and E2F targets. KU-55933 was predicted as a putative therapeutic drug for BC targeting VAMP7. CONCLUSIONS: VAMP7 was upregulated in BC tissue and correlated with poor prognosis of BC patients. VAMP7 may promote BC progression by targeting the cell cycle pathway.

A Flexible and Wearable Photodetector Enabling Ultra-Broadband Imaging from Ultraviolet to Millimeter-Wave Regimes.

Flexible and miniaturized photodetectors, offering a fast response across the ultraviolet (UV) to millimeter (MM) wave spectrum, are crucial for applications like healthcare monitoring and wearable optoelectronics. Despite their potential, developing such photodetectors faces challenges due to the lack of suitable materials and operational mechanisms. Here, the study proposes a flexible photodetector composed of a monolayer graphene connected by two distinct metal electrodes. Through the photothermoelectric effect, these asymmetric electrodes induce electron flow within the graphene channel upon electromagnetic wave illumination, resulting in a compact device with ultra-broadband and rapid photoresponse. The devices, with footprints ranging from 3 × 20 µm2 to 50 × 20 µm2, operate across a spectrum from 325 nm (UV) to 1.19 mm (MM) wave. They demonstrate a responsivity (RV) of up to 396.4 ± 5.1 mV W-1, a noise-equivalent power (NEP) of 8.6 ± 0.1 nW Hz- 0.5, and a response time as small as 0.8 ± 0.1 ms. This device facilitates direct imaging of shielded objects and material differentiation under simulated human body-wearing conditions. The straightforward device architecture, aligned with its ultra-broadband operational frequency range, is anticipated to hold significant implications for the development of miniaturized, wearable, and portable photodetectors.

A multimode photodetector with polarization-dependent near-infrared responsivity using the tunable split-dual gates control.

As the limited carrier densities in atomic thin materials can be well controlled by electrostatic gates, p-n junctions based on two-dimensional materials in the coplanar split-gate configuration can work as photodetectors or light-emitting diodes. These coplanar gates can be fabricated in a simple one-step lithography process and are frequently used in hybrid integration with on-chip optical structures. However, the polarization-dependent responsivity of such a configuration is less explored in the near-infrared band, and a clear understanding is still missing. Here we fabricate near-infrared tunable multiple modes twisted bilayer graphene photodetector enabled by the coplanar split-gate control and confirm that the photothermoelectric effect governs the photovoltage mechanism of the p-n junction mode. Our study also elucidates that the discrepancy of the responsivities under different linear polarizations is owing to the different cavity modes and provides a valuable example for designing chip-integrated optoelectronic devices.

Effects of lower body positive pressure treadmill on functional improvement in knee osteoarthritis: A randomized clinical trial study.

BACKGROUND: Knee joint pain and stiffness are the two main symptoms of knee osteoarthritis (OA) and thus restrict a patient's activities, such as walking and walking up and downstairs. The lower body positive pressure (LBPP) treadmill as one of the emerging body weight support system devices brings new hope for exercise-related rehabilitation for knee OA patients. AIM: To investigate the biomechanical effects and the subjective clinical assessment of LBPP treadmill walking exercise when compared with conventional therapy in mild to moderate knee OA patients. METHODS: Eighteen patients with mild-to-moderate knee OA were recruited in this randomized controlled trial (RCT) study. The eligible knee OA patients were randomly assigned to two groups: LBPP and control groups. The patients in the LBPP group performed an LBPP walking training program for 30 min/session per day, 6 d per week for 2 wk whereas the patients in the control group performed walking on the ground for the same amount. All patients underwent clinical assessments and three-dimensional gait analysis at pre- and 2-wk post-treatment. RESULTS: The Western Ontario and McMaster Universities Arthritis Index and visual analog scale scores in both the LBPP group and control group were found to decrease significantly at the post-treatment point than the pre-treatment point (LBPP: 70.25 ± 13.93 vs 40.50 ± 11.86; 3.88 ± 0.99 vs 1.63 ± 0.52; control: 69.20 ± 8.88 vs 48.10 ± 8.67; 3.80 ± 0.79 vs 2.60 ± 0.70, P < 0.001). Moreover, compared with the control group, the LBPP group showed more improvements in walking speed (P = 0.007), stride length (P = 0.037), and knee range of motion (P = 0.048) during walking, which represented more improvement in walking ability. CONCLUSION: The results of our RCT study showed that the LBPP group has a greater effect on improving gait parameters than the conventional group, although there was no significant advantage in clinical assessment. This finding indicates that LBPP treadmill walking training might be an effective approach for alleviating pain symptoms and improving lower extremity locomotion in mild to moderate knee OA patients.

[Effects of radix morindae from different processed products on anti-hypoxia and reproductive system of mice].

OBJECTIVE: To investigate the effects of Radix Morindae from different processed products on anti-hypoxia and reproductive system of mice. METHODS: The experimental study on anti-hypoxia was through the anti-anoxia action under normal-pressure, sodium nitrite poisoning and acute cerebral ischemia anoxia test; the experimental study on reproductive system was through observing the testis weight of immature male mice and the development of accessory sex organs in castrated mice. RESULTS: Both Radix Morindae of drying product and salt product could markedly increase the mice breathing time under acute cerebral ischemia anoxia, the salt product also could markedly increase the breathing frequency, prolong the mice survival time under atmospheric hypoxia and increase the testis weight of immature male mice. CONCLUSION: Both Radix Morindae of drying product and salt product can enhance anti-hypoxia and reproductive system of mice, and the effect of the salt product was superior to the drying product.

Fabrication of Two-Dimensional Crystalline Organic Films by Tilted Spin Coating for High-Performance Organic Field-Effect Transistors.

We developed a facile method for fabricating large-area, two-dimensional (2D), organic, highly crystalline films and extended it to organic thin-film transistor arrays. Tilted spinning provided oriented flow at the three-phase contact line, and a 2D crystalline film that consisted of layer-by-layer stacked 2,7-diocty[1]benzothieno[3,2- b]benzothiophene (C8-BTBT) was obtained facilely for organic thin-film transistors (OTFTs). The extracted field-effect mobility is 4.6 cm2 V-1 s-1, but with nonideal features. By applying this method to microdroplet arrays, an oriented crystal was fabricated, and the channel region for OTFTs was covered by adjusting the spinning speed. By tuning the tilt angle (θ) of the revolving substrate, we fabricated high-performance OTFT arrays with average and maximum mobilities of 7.5 and 10.1 cm2 V-1 s-1, respectively, which exhibited high reliability factors of over 90% and were close to that of ideal transistors. These results suggest that high-quality crystalline films can be obtained via a facile tilted-spinning method.

A phiC31 integrase-mediated integration hotspot in favor of transgene expression exists in the bovine genome.

phiC31 integrase, a site-specific recombinase, can effectively mediate foreign genes bearing an attB sequence integrated into pseudo attP sites. We have previously identified two pseudo attP sites, BpsF1 and BpsM1 from the bovine genome. In this study, two new pseudo attP sites, BF4 and BF10, were discovered using half-nested inverse PCR from cow fibroblasts. The genomic locations of these two pseudo attP sites were identified by direct sequencing and a BLAST search, and it was confirmed that they reside at positions 4q31 and 10q35 by fluorescence in situ hybridization analysis. Subsequently, the distinct integration frequencies of the four pseudo attP sites were examined. The BF4 site was identified as a hotspot where site-specific integration occurred in most of the cell clones examined, accounting for 74% (42/57) of the integration; much more than the integration frequency for BF10 (7%; 4/57), BpsF1 (7%; 4/57) and BpsM1 (0/57). Interestingly, similar to other hotspots identified in the human and mouse genomes, in which transgenes integrated at hotspots result in high expression, the GFP gene integrated at hotspot BF4 was expressed at high levels in cow fibroblasts, as confirmed by fluorescence microscopy and FACS analysis. Furthermore, ELISA showed that the expression level of the GFP gene integrated at the BF4 site averaged approximately 328 microg x mg(-1), which is more than twofold higher than that integrated at the BF10 site. This study suggests that somatic cells carrying a desired gene integrated at the BF4 site can be used as nuclear donors to generate valuable transgenic animals by nuclear transfer.

[Dynamic monitoring of serum human chorionic gonadotropin beta-subunit levels for early diagnosis of ectopic pregnancy].

OBJECTIVE: To assess the value of monitoring serum human chorionic gonadotropin beta-subunit (beta-HCG) level changes in early diagnosis of ectopic pregnancy. METHODS: Totalling 106 cases of ectopic pregnancy and 69 cases of threatened abortion were included in the study. Blood samples were collected to examine beta-HCG levels, which was repeated 2-3 days later. RESULTS: Initial serum beta-HCG levels of the women with ectopic pregnancy and different were significantly lower than those in women with threatened abortion (P<0.05), and the increment rate of serum beta-HCG in the former was also significantly lower (P<0.05). CONCLUSION: Compared with single-time serum beta-HCG detection, dynamic monitoring of serum beta-HCG provides more important and reliable evidence for early diagnosis of ectopic pregnancy. Transvaginal ultrasonography and in should also be considered in the clinical analysis.