MS4A3 Promotes the Chemosensitivity of Lung Cancer via THAP1/EGFR Pathways.

MS4A3 functions as a tumor suppressor in multiple cancer types. However, the roles of MS4A3 in lung cancer are still unknown. Therefore, this study aims to investigate the potentials of MS4A3 in lung cancer. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was carried out to determine mRNA expression. CCK-8 and colony formation assay are conducted to determine cell proliferation. Tube formation assay is performed to determine angiogenesis. Flow cytometry is used to determine cell apoptosis. JASPAR is used to analyze the binding motif of THAP1. Luciferase and ChIP assay are conducted to verify whether MS4A3 can interact with THAP1 to transcriptionally inactivate EGFR. The results showed that MS4A3 is downregulated in non-small-cell lung cancer (NSCLC) patients, which predicts poor clinical outcomes of NSCLC patients. Overexpressed MS4A3 enhances the chemosensitivity of NSCLC cells to osimertinib, whereas MS4A3 knockdown exerts the opposite effects. MS4A3 suppresses the proliferation and angiogenesis and promotes the apoptosis of NSCLC cells. Moreover, MS4A3 upregulates apoptosis-related THAP1 to inactivate EGFR. However, THAP1 knockdown attenuates the effects of MS4A3 and promotes the malignant behavior of NSCLC cells. In conclusion, MS4A3 functions as an anti-tumor gene in NSCLC. MS4A3/THAP1/EGFR signaling enhances the chemosensitivity of lung cancer to EGFR tyrosine kinase inhibitor (TKI).

How does TCR-T cell therapy exhibit a superior anti-tumor efficacy.

TCR-engineered T cells have achieved great progress in solid tumor therapy, some of which have been applicated in clinical trials. Deep knowledge about the current progress of TCR-T in tumor therapy would be beneficial to understand the direction. Here, we classify tumor antigens into tumor-associated antigens, tumor-specific antigens, tumor antigens expressed by oncogenic viruses, and tumor antigens caused by abnormal protein modification; Then we detail the TCR-T cell therapy effects targeting those tumor antigens in clinical or preclinical trials, and propose that neoantigen specific TCR-T cell therapy is expected to be a promising approach for solid tumors; Furthermore, we summarize the optimization strategies, such as tumor microenvironment, TCR pairing and affinity, to improve the therapeutic effect of TCR-T. Overall, this review provides inspiration for the antigen selection and therapy strategies of TCR-T in the future.

The efficacy and safety of intravenous tirofiban in the treatment of acute ischemic stroke patients with early neurological deterioration.

WHAT IS KNOWN AND OBJECTIVE: Many patients with acute ischemic stroke (AIS) develop early neurological deterioration (END), leading to disabilities or death. Thus, this study aimed to investigate the efficacy and safety of intravenous tirofiban in treating patients with AIS and END who missed the thrombolysis time window. METHODS: A total of 123 AIS-END patients participated in the study between January 2021 and December 2021. Patients were randomized into the tirofiban group (n = 63) and the control group (n = 60) based on whether a tirofiban injection was administered. The National Institute of Health Stroke Scale (NIHSS) was used to assess neurological function at the 48th hour and on the 7th day after intervention, and the modified Rankin Scale (mRS) was used to assess neurological recovery 90 days after AIS. Adverse reactions during the intervention were recorded for safety analysis. RESULTS AND DISCUSSION: The 7th day NIHSS and 90th day post-AIS mRS scores of the tirofiban group were significantly lower than those of the control group (p < 0.05), while the 90th day good prognosis (mRS ≤ 2) rate of the tirofiban group was significantly higher (84.13% vs. 65.00%, p < 0.05). Logistic regression demonstrated a protective effect of tirofiban for good prognosis in AIS patients with END (OR = 4.675, 95% CI [1.012-21.605], p < 0.05). No cases of intracranial haemorrhage transformation or death were observed during the treatment in either group. WHAT IS NEW AND CONCLUSION: Tirofiban injection exhibited a high safety profile and significantly improved the prognosis of AIS-END patients who missed the intravenous thrombolysis time window.

Circ_0074027 contributes to non-small cell lung cancer progression through positively modulating RHOA via sequestering miR-2467-3p.

Non-small cell lung cancer (NSCLC) is a common cancer with an unfavorable 5-year survival rate. We intended to explore the role of circular RNA_0074027 (circ_0074027) in NSCLC progression. The levels of circ_0074027, messenger RNA (mRNA) of its linear form paired like homeodomain 1 (PITX1), microRNA-2467-3p (miR-2467-3p) and ras homolog family member A (RHOA) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8) assay and plate colony assay were conducted to measure the proliferation ability of NSCLC cells. Transwell assays were used to assess cell migration and invasion abilities. Flow cytometry was utilized to analyze cell apoptosis rate. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to test the interaction between miR-2467-3p and circ_0074027 or RHOA. Western blot assay was performed to evaluate the protein level of RHOA in NSCLC cells. Murine xenograft model was built to evaluate the role of circ_0074027 in tumor growth in vivo. Circ_0074027 expression was prominently elevated in NSCLC tissues and cell lines. Circ_0074027 knockdown or miR-2467-3p overexpression suppressed cell proliferation, migration and invasion and facilitated cell apoptosis of NSCLC cells. Circ_0074027 interacted with miR-2467-3p, and RHOA was a target of miR-2467-3p in NSCLC cells. RHOA silencing blocked the malignant potential of NSCLC cells. Circ_0074027 silencing restrained the malignant phenotypes of NSCLC cells largely through up-regulating miR-2467-3p. Circ_0074027 knockdown notably blocked xenograft tumor growth in vivo. In conclusion, circ_0074027 accelerated NSCLC progression by binding to miR-2467-3p to induce RHOA expression.

Knockdown of long noncoding RNA XIST alleviates oxidative low-density lipoprotein-mediated endothelial cells injury through modulation of miR-320/NOD2 axis.

Atherosclerosis remains to be one of the most common vascular disorders resulting in morbidity and mortality in the world. Recent studies suggested that endothelial cells (ECs) injury caused by oxidative low-density lipoprotein (ox-LDL) is an early marker for atherosclerosis. Nevertheless, the mechanisms of ox-LDL-induced ECs injury are complicated and largely unknown. Here, we found lncRNA XIST (X-inactive specific transcript) was upregulated in human umbilical vein endothelial cells (HUVECs) stimulated by ox-LDL. Knockdown of XIST boosted the cell viability and suppressed cell apoptosis under ox-LDL stimuli. Further experiments identified XIST regulated the expression of Nucleotide-Binding Oligomerization Domain 2 (NOD2) by sponging miR-320. XIST silencing exerted a protective effect on ox-LDL-induced HUVECs injury via miR-320/NOD2 regulatory network. Our data provide insight into the role of the lncRNA XIST in ox-LDL mediated ECs injury, which can aid in developing new therapeutic strategies for the treatment of atherosclerosis.

Fiber-optic anemometer based on single-walled carbon nanotube coated tilted fiber Bragg grating.

In this work, a novel and simple optical fiber hot-wire anemometer based on single-walled carbon nanotubes (SWCNTs) coated tilted fiber Bragg grating (TFBG) is proposed and demonstrated. For the hot-wire wind speed sensor design, TFBG is an ideal in-fiber sensing structure due to its unique features. It is utilized as both light coupling and temperature sensing element without using any geometry-modified or uncommon fiber, which simplifies the sensor structure. To further enhance the thermal conversion capability, SWCNTs are coated on the surface of the TFBG instead of traditional metallic materials, which have excellent thermal characteristics. When a laser light is pumped into the sensor, the pump light propagating in the core will be easily coupled into cladding of the fiber via the TFBG and strongly absorbed by the SWCNTs thin film. This absorption acts like a hot-wire raising the local temperature of the fiber, which is accurately detected by the TFBG resonance shift. In the experiments, the sensor's performances were investigated and controlled by adjusting the inherent angle of the TFBG, the thickness of SWCNTs film, and the input power of the pump laser. It was demonstrated that the developed anemometer exhibited significant light absorption efficiency up to 93%, and the maximum temperature of the local area on the fiber was heated up to 146.1°C under the relatively low pump power of 97.76 mW. The sensitivity of -0.3667 nm/(m/s) at wind speed of 1.0 m/s was measured with the selected 12° TFBG and 1.6 µm film.

A Novel Low-Power-Consumption All-Fiber-Optic Anemometer with Simple System Design.

A compact and low-power consuming fiber-optic anemometer based on single-walled carbon nanotubes (SWCNTs) coated tilted fiber Bragg grating (TFBG) is presented. TFBG as a near infrared in-fiber sensing element is able to excite a number of cladding modes and radiation modes in the fiber and effectively couple light in the core to interact with the fiber surrounding mediums. It is an ideal in-fiber device used in a fiber hot-wire anemometer (HWA) as both coupling and sensing elements to simplify the sensing head structure. The fabricated TFBG was immobilized with an SWCNT film on the fiber surface. SWCNTs, a kind of innovative nanomaterial, were utilized as light-heat conversion medium instead of traditional metallic materials, due to its excellent infrared light absorption ability and competitive thermal conductivity. When the SWCNT film strongly absorbs the light in the fiber, the sensor head can be heated and form a "hot wire". As the sensor is put into wind field, the wind will take away the heat on the sensor resulting in a temperature variation that is then accurately measured by the TFBG. Benefited from the high coupling and absorption efficiency, the heating and sensing light source was shared with only one broadband light source (BBS) without any extra pumping laser complicating the system. This not only significantly reduces power consumption, but also simplifies the whole sensing system with lower cost. In experiments, the key parameters of the sensor, such as the film thickness and the inherent angle of the TFBG, were fully investigated. It was demonstrated that, under a very low BBS input power of 9.87 mW, a 0.100 nm wavelength response can still be detected as the wind speed changed from 0 to 2 m/s. In addition, the sensitivity was found to be -0.0346 nm/(m/s) under the wind speed of 1 m/s. The proposed simple and low-power-consumption wind speed sensing system exhibits promising potential for future long-term remote monitoring and on-chip sensing in practical applications.

Clinical efficacy of femtosecond laser-assisted phacoemulsification in diabetic cataract patients.

BACKGROUND: Diabetic patients with cataracts encounter specific difficulties during cataract surgery due to alterations in microcirculation, blood supply, metabolism, and the microenvironment. Traditional phacoemulsification may not fully tackle these issues, especially in instances with substantial preoperative astigmatism. The utilization of femtosecond laser-assisted phacoemulsification, in conjunction with Toric intraocular lens (IOL) implantation, offers a potentially more efficient strategy. This research seeks to evaluate the efficacy and possible complications of this approach in diabetic cataract patients. AIM: To investigate the clinical efficacy and complications of femtosecond laser-assisted phacoemulsification combined with Toric IOL implantation in diabetic cataract patients, comparing it with traditional phacoemulsification methods. METHODS: This retrospective study enrolled 120 patients with diabetes cataract from May 2019 to May 2021. The patients were divided into two groups: the control group underwent traditional phacoemulsification and Toric IOL implantation, while the treatment group received Len Sx femtosecond laser-assisted treatment. Outcome measures included naked eye vision, astigmatism, high-level ocular phase difference detection, clinical efficacy, and complication. RESULTS: There were no significant preoperative differences in astigmatism or naked eyesight between the two groups. However, postoperative improvements were observed in both groups, with the treatment group showing greater enhancements in naked eye vision and astigmatism six months after the procedure. High-level corneal phase difference tests also indicated significant differences in favor of the treatment group. CONCLUSION: This study suggests that femtosecond laser-assisted phacoemulsification combined with Toric IOL implantation appears to be more effective in enhancing postoperative vision in diabetic cataract patients compared to traditional methods offering valuable insights for clinical practice.

Biopsy forceps are useful for measuring esophageal varices in vitro.

BACKGROUND: To avoid acute variceal bleeding in cirrhosis, current guidelines recommend screening for high-risk esophageal varices (EVs) by determining variceal size and identifying red wale markings. However, visual measurements of EV during routine endoscopy are often inaccurate. AIM: To determine whether biopsy forceps (BF) could be used as a reference to improve the accuracy of binary classification of variceal size. METHODS: An in vitro self-made EV model with sizes ranging from 2 to 12 mm in diameter was constructed. An online image-based survey comprising 11 endoscopic images of simulated EV without BF and 11 endoscopic images of EV with BF was assembled and sent to 84 endoscopists. The endoscopists were blinded to the actual EV size and evaluated the 22 images in random order. RESULTS: The respondents included 48 academic and four private endoscopists. The accuracy of EV size estimation was low in both the visual (13.81%) and BF-based (20.28%) groups. The use of open forceps improved the ability of the endoscopists to correctly classify the varices by size (small ≤ 5 mm, large > 5 mm) from 71.85% to 82.17% (P < 0.001). CONCLUSION: BF may improve the accuracy of EV size assessment, and its use in clinical practice should be investigated.

Advances, opportunities and challenges in developing therapeutic cancer vaccines.

Therapeutic cancer vaccines have shown promising efficacy in helping immunotherapy for cancer patients, but the systematic characterization of the clinical application and the method for improving efficacy is lacking. Here, we mainly summarize the classification of therapeutic cancer vaccines, including protein vaccines, nucleic acid vaccines, cellular vaccines and anti-idiotypic antibody vaccines, and subdivide the above vaccines according to different types and delivery forms. Additionally, we outline the clinical efficacy and safety of vaccines, as well as the combination strategies of therapeutic cancer vaccines with other therapies. This review will provide a detailed overview and rationale for the future clinical application and development of therapeutic cancer vaccines.

Oral Microbiota Profile in a Group of Anti-AChR Antibody-Positive Myasthenia Gravis Patients.

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies directed against the postsynaptic membrane at the neuromuscular junction. Perturbation of gut microbiota is thought to contribute to the development of MG, as reflected by fecal metabolomic signatures in humans, but there have been few studies on the relationship between oral microbiota profile and MG. The current study evaluated the correlation between oral microbiota composition and diversity and anti-acetylcholinereceptor (AChR) antibody-positive MG by comparing oral microbiota communities of patients (n = 20) and healthy controls (HCs; n = 20) by 16S rRNA gene sequencing. Principal coordinate analysis and Adonis analysis revealed significant differences in oral microflora profile between the twogroups. Compared to HCs, the abundance of the phyla Firmicutes and Actinobacteria and genera Streptococcus, Rothia, and Lachnoanerobaculum was significantly increased whereas that of phyla Proteobacteria and Spirochaetotaand genera Neisseria, Haemophilus, and Treponema was significantly decreased in MG patients. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the biosynthesis of ansamycins and amino acid metabolism pathways were altered in MG. These results indicate that oral microbiota composition is perturbed in patients with anti-AChR antibody-positive MG, providing new potential avenues for targeted therapeutic interventions.

The clinical effects of sodium hyaluronate, polyethylene glycol, and dextran-70 eye drops in relieving dry eye after phacoemulsification.

ABSTRACT: To compare the clinical efficacy of sodium hyaluronate eye drops, polyethylene glycol eye drops, and compound dextran eye drops in the treatment of dry eye after phacoemulsification of cataract.A total of 99 patients with dry eye after cataract phacoemulsification combined with intraocular lens implantation were treated in our hospital. Patients were divided into group A (sodium hyaluronate eye drops), group B (polyethylene glycol eye drops), and group C (dextran-70 eye drops). The clinical effect, tear film breakup time, basic tear secretion, corneal staining score, dry eye symptom score, and the incidence of ocular irritation were assessed.On the 3rd, 15th, 30th, and 60th day after operation, the tear film breakup time, corneal staining score, Schirmer I test, and dry eye symptom score in group A and group B were better than those in group C (P < .05). In addition, there were no significant differences in tear breakdown time, corneal staining score, Schirmer I test, and dry eye symptom score between group A and group B (P > .05). At 3 days to 60 days after operation, the incidence of dry eye in group A (12.12%) and group B (18.18%) was lower than that in group C (39.39%), and the incidence of dry eye in group A was significantly lower than that in group B (P < .05).The effect of sodium hyaluronate eye drops elicited a greater beneficial impact as compared to polyethylene glycol eye drops and dextran-70 eye drops.

Impact of the COVID-19 Pandemic on Acute Upper Gastrointestinal Bleeding in Xingtai City.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) has severely impacted the daily practice of gastrointestinal endoscopy worldwide. Most endoscopy centers in China were shut down in late January 2020. We investigated the impact of the shutdown on acute upper gastrointestinal bleeding (AUGIB) events in Xingtai City, Hebei Province, China. METHODS: A web-based survey collected information on gastroscopy workload and AUGIB events. The study period was from 4 weeks before to 4 weeks after lockdown initiation in Xingtai City. Fourteen public gastrointestinal endoscopy centers performing emergency endoscopies were contacted via e-mail to collect weekly emergency gastroscopy volumes and the number of AUGIB events. AUGIB was defined as recent melena, hematemesis, or both, with an endoscopically visible source of bleeding. RESULTS: Twelve (85.7%) of the 14 surveyed gastrointestinal endoscopy centers in the city- and county-level hospitals responded. Altogether, 4,045 and 1,077 gastroscopy procedures were performed 4 weeks before and after lockdown initiation (73.4% reduction), respectively. Peptic ulcer-related AUGIB and variceal AUGIB events showed a 58.5% and 52.9% decline, respectively, compared with pre-COVID-19 data. Although the absolute number of AUGIB events decreased during the pandemic (from 149 to 66), the likelihood of detecting AUGIB during gastroscopy increased (3.68% (pre-COVID-19 period) versus 6.13% (COVID-19 period); P < 0.05). CONCLUSION: The COVID-19 pandemic resulted in a considerable reduction in gastroscopy workload and AUGIB events; however, the likelihood of detecting AUGIB increased significantly during gastroscopies.

Aggregation kinetics of UV-aged soot nanoparticles in wet environments: Effects of irradiation time and background solution chemistry.

Soot nanoparticles (SNPs) undergo aging processes in aqueous systems, altering their physicochemical properties and affecting their fate and transport. This study investigated the aging effects via ultraviolet irradiation on aggregation kinetics of SNPs in water. The results showed that, compared to fresh SNPs, those irradiated for 1 day aggregated more easily in NaCl and CaCl2 solutions, with reduction of critical coagulation concentrations by 72% and 40%, respectively. Similar phenomena were found in additional six electrolyte solutions, and SNPs irradiated for > 3 days had no measurable difference in aggregation rate. The aggregation-enhancement of irradiated SNPs was more prominent at low electrolyte concentrations and pH > 4. However, in the presence of macromolecules, irradiated SNPs could be stabilized against aggregation via steric hindrance with strength of bovine serum albumin > humic acid > alginate > fulvic acid, whereas alginate further destabilized aged SNPs via calcium bridging. The fitted Hamaker constant increased from 7.8 × 10-20 (fresh) to 1.2 × 10-19 J (7-day irradiated), suggesting that decarboxylation during irradiation may weaken electrical repulsion and enhance van der Waals attraction, promoting aggregation. These results demonstrated the vital role of UV-induced aging in fate and transport of SNPs in wet environments.