Development of erythrina-based PARP-1/FTase dual-target inhibitors against lung cancer epithelial-mesenchymal transition (EMT) in vivo and in vitro.

A novel series of erythrina derivatives as PARP-1/FTase inhibitors were synthesized, and evaluated for their biological activities. Compound T9 had excellent inhibitory effects on cell viability (A549: IC50 = 1.74 µM; A549/5-Fu: IC50 = 1.03 µM) and in vitro enzyme activities (PARP-1: IC50 = 0.40 µM; FTase: IC50 = 0.067 µM). Molecular docking and point mutation assays demonstrated the interaction of compound T9 with key amino acid residues. The compound T9 exhibited potent anti-proliferation and anti-migration capabilities against A549 and A549/5-Fu cells. PCR array and western blot results showed that compound T9 could effectively inhibit EMT-related proteins in A549 and A549/5-Fu cells, thereby inhibiting the development of lung cancer. Importantly, compound T9 could significantly inhibit tumor growth in the A549 xenograft tumor model (TGI = 65.3 %). In conclusion, this study was the first presentation of the concept of dual-target inhibitors of the PARP-1/FTase enzymes. It also provides the basis for further research and development of novel PARP-1/FTase inhibitors.

Preparation and epitope analysis of monoclonal antibodies against African swine fever virus DP96R protein.

BACKGROUND: Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV. RESULTS: Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined. CONCLUSION: Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology.

Decomposition of exotic versus native aquatic plant litter in a lake littoral zone: Stoichiometry and life form analyses.

The decomposition rates and stoichiometric characteristics of many aquatic plants remain unclear, and our understanding of material flow and nutrient cycles within freshwater ecosystems is limited. In this study, an in-situ experiment involving 23 aquatic plants (16 native and 7 exotic species) was carried out via the litter bag method for 63 days, during which time the mass loss and nutrient content (carbon (C), nitrogen (N), and phosphorus (P)) of plants were measured. Floating-leaved plants exhibited the highest decomposition rate (0.038 ± 0.002 day-1), followed by submerged plants and free-floating plants (0.029 ± 0.002 day-1), and emergent plants had the lowest decomposition rate (0.019 ± 0.001 day-1). Mass loss by aquatic plants correlated with stoichiometric characteristics; the decomposition rate increased with an increasing P content and with a decreasing C content, C:N ratio, and C:P ratio. Notably, the decomposition rate of submerged exotic plants (0.044 ± 0.002 day-1) significantly exceeded that of native plants (0.026 ± 0.004 day-1), while the decomposition rate of emergent exotic plants was 55 ± 4 % higher than that of native plants. The decomposition rates of floating-leaved and free-floating plants did not significantly differ between the native and exotic species. During decomposition, emergent plants displayed an increase in C content and a decrease in N content, contrary to patterns observed in other life forms. The P content decreased for submerged (128 ± 7 %), emergent (90 ± 5 %), floating-leaved (104 ± 6 %), and free-floating plants (32 ± 6 %). Exotic plants released more C and P but accumulated more N than did native plants. In conclusion, the decomposition of aquatic plants is closely linked to litter quality and influences nutrient cycling in freshwater ecosystems. Given these findings, the invasion of the littoral zone by submerged and emergent exotic plants deserves further attention.

Low-loss tantalum pentoxide photonics with a CMOS-compatible process.

We report a Ta2O5 photonic platform with a propagation loss of 0.49 dB/cm at 1550 nm, of 0.86 dB/cm at 780 nm, and of 3.76 dB/cm at 2000 nm. The thermal bistability measurement is conducted in the entire C-band for the first time to reveal the absorption loss of Ta2O5 waveguides, offering guidelines for further reduction of the waveguide loss. We also characterize the Ta2O5 waveguide temperature response, which shows favorable thermal stability. The fabrication process temperature is below 350°C, which is friendly to integration with active optoelectronic components.

Performance of ChatGPT on the Chinese Postgraduate Examination for Clinical Medicine: Survey Study.

BACKGROUND: ChatGPT, an artificial intelligence (AI) based on large-scale language models, has sparked interest in the field of health care. Nonetheless, the capabilities of AI in text comprehension and generation are constrained by the quality and volume of available training data for a specific language, and the performance of AI across different languages requires further investigation. While AI harbors substantial potential in medicine, it is imperative to tackle challenges such as the formulation of clinical care standards; facilitating cultural transitions in medical education and practice; and managing ethical issues including data privacy, consent, and bias. OBJECTIVE: The study aimed to evaluate ChatGPT's performance in processing Chinese Postgraduate Examination for Clinical Medicine questions, assess its clinical reasoning ability, investigate potential limitations with the Chinese language, and explore its potential as a valuable tool for medical professionals in the Chinese context. METHODS: A data set of Chinese Postgraduate Examination for Clinical Medicine questions was used to assess the effectiveness of ChatGPT's (version 3.5) medical knowledge in the Chinese language, which has a data set of 165 medical questions that were divided into three categories: (1) common questions (n=90) assessing basic medical knowledge, (2) case analysis questions (n=45) focusing on clinical decision-making through patient case evaluations, and (3) multichoice questions (n=30) requiring the selection of multiple correct answers. First of all, we assessed whether ChatGPT could meet the stringent cutoff score defined by the government agency, which requires a performance within the top 20% of candidates. Additionally, in our evaluation of ChatGPT's performance on both original and encoded medical questions, 3 primary indicators were used: accuracy, concordance (which validates the answer), and the frequency of insights. RESULTS: Our evaluation revealed that ChatGPT scored 153.5 out of 300 for original questions in Chinese, which signifies the minimum score set to ensure that at least 20% more candidates pass than the enrollment quota. However, ChatGPT had low accuracy in answering open-ended medical questions, with only 31.5% total accuracy. The accuracy for common questions, multichoice questions, and case analysis questions was 42%, 37%, and 17%, respectively. ChatGPT achieved a 90% concordance across all questions. Among correct responses, the concordance was 100%, significantly exceeding that of incorrect responses (n=57, 50%; P<.001). ChatGPT provided innovative insights for 80% (n=132) of all questions, with an average of 2.95 insights per accurate response. CONCLUSIONS: Although ChatGPT surpassed the passing threshold for the Chinese Postgraduate Examination for Clinical Medicine, its performance in answering open-ended medical questions was suboptimal. Nonetheless, ChatGPT exhibited high internal concordance and the ability to generate multiple insights in the Chinese language. Future research should investigate the language-based discrepancies in ChatGPT's performance within the health care context.

First-line treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetic population at low risk of cardiovascular disease: a meta-analysis.

Background: The benefit of first-line use of sodium-dependent glucose transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) with low risk of cardiovascular diseases are not clear. Methods: PubMed, EMBASE and Cochrane Library databases were searched to identify eligible randomized controlled trials. We used the odds ratio (OR) and mean difference (MD) and the corresponding 95% confidence interval (CI) to assess the dichotomous and continuous variable, respectively. Results: Thirteen studies involving 2,885 T2DM at low risk of cardiovascular diseases were included. Compared to placebo, first line use of SGLT2i significantly reduced glycosylated hemoglobin type A1C (HbA1c) (MD: -0.72), weight (MD: -1.32) and fasting plasma glucose (FPG) (MD: -27.05) levels. Compared with metformin, SGLT2i reduced body weight (MD: -1.50) and FPG (MD: -10.13) more effectively, with similar reduction for HbA1c (MD: -0.05). No significant increased safety adverse was found for SGLT2i, including nasopharyngitis (OR: 1.07), urinary tract infection (OR: 2.31), diarrhea (OR: 1.18) and hypoglycemia (OR: 1.06). GLP-1RAs significantly reduced HbA1c (MD: -1.13), weight (MD: -2.12) and FPG (MD: -31.44) levels as first-line therapy compared to placebo. GLP-1RAs significantly increased occurrence of diarrhea (OR: 2.18), hypoglycemia (OR: 3.10), vomiting (OR: 8.22), and nausea (OR: 4.41). Conclusion: First line use of SGLT2i and GLP-1RAs is effective in reducing HbA1c, weight, and FPG levels in T2DM patients at low risk for cardiovascular disease. SGLT2i may be superior to metformin in controlling body weight and FPG. GLP-1RAs may increase the occurrence of diarrhea, hypoglycemia, vomiting, and nausea. Systematic review registration: PROSPERO (International Prospective Register of Systematic Reviews. https://www.york.ac.uk/inst/crd, CRD42022347233).

Using Abundant 1H Polarization to Enhance the Sensitivity of Solid-State NMR Spectroscopy.

Solid-state NMR spectroscopy has been playing a significant role in elucidating the structures and dynamics of materials and proteins at the atomic level for decades. As an extremely abundant nucleus with a very high gyromagnetic ratio, protons are widely present in most organic/inorganic materials. Thus, this Perspective highlights the advantages of proton detection at fast magic-angle spinning (MAS) and presents strategies to utilize and exhaust 1H polarization to achieve signal sensitivity enhancement of solid-state NMR spectroscopy, enabling substantial time savings and extraction of more structural and dynamics information per unit time. Those strategies include developing sensitivity-enhanced single-channel 1H multidimensional NMR spectroscopy, implementing multiple polarization transfer steps in each scan to enhance low-γ nuclei signals, and making full use of 1H polarization to obtain homonuclear and heteronuclear chemical shift correlation spectra in a single experiment. Finally, outlooks and perspectives are provided regarding the challenges and future for the further development of sensitivity-enhanced proton-based solid-state NMR spectroscopy.

The role of receptors in the cross-species spread of coronaviruses infecting humans and pigs.

The pandemic caused by SARS-CoV-2, which has proven capable of infecting over 30 animal species, highlights the critical need for understanding the mechanisms of cross-species transmission and the emergence of novel coronavirus strains. The recent discovery of CCoV-HuPn-2018, a recombinant alphacoronavirus from canines and felines that can infect humans, along with evidence of SARS-CoV-2 infection in pig cells, underscores the potential for coronaviruses to overcome species barriers. This review investigates the origins and cross-species transmission of both human and porcine coronaviruses, with a specific emphasis on the instrumental role receptors play in this process.

Effects of aerobic and combined aerobic-resistance exercise on motor function in sedentary older adults: A randomized clinical trial.

BACKGROUND: Sedentary behavior is widespread among older adults and accelerates the decline of motor function. Nevertheless, there is insufficient evidence concerning the effectiveness of regular exercise in enhancing the same in sedentary older adults. OBJECTIVE: To compare the effects of 24 weeks of aerobic and combined aerobic-resistance exercise on the motor function of sedentary older adults. METHODS: Sixty healthy sedentary older (65-80 years) were randomly enrolled. Participants were randomly divided into 3 groups (1:1:1): aerobic exercise group (AEG), combined aerobic-resistance exercise group (CEG), and health education group (HEG). The training group underwent a five-day-a-week regimen, with each session lasting for 40 minutes (including 10 min warm-up and cool-down). HEG received only monthly health lectures. We assessed lower limb muscle strength (30-second sit-to-stand ability), single-dual task gait, static and dynamic balance functions at baseline and after 24 weeks of intervention using per-protocol analysis. RESULTS: Among 60 elderly healthy who were randomized (mean age 70.59 ± 3.31 years; 28 women (46%)), 42 (70%) completed the evaluation after 24 weeks. Both the aerobic exercise and combined aerobic-resistance exercise groups exhibited improved 30-second sit-to-stand ability, static balance in closed-eye standing mode, and dynamic balance (P< 0.05). However, there were no statistically significant changes in the single-task gait parameters of stride length, stride width, and stride speed (P> 0.05). Additionally, compared to the aerobic exercise group, the combined exercise group showed an increase in dual-task gait speed and medial and lateral dynamic stability indices (P< 0.05). CONCLUSION: Both the aerobic exercise and combined aerobic-resistance exercise programs are effective in enhancing lower limb muscle strength, dynamic balance, and static balance while standing with eyes closed in sedentary older adults. Furthermore, the combined aerobic-resistance exercise program is more effective in improving dual-task gait speed as well as medial and lateral dynamic balance.

How does ChatGPT-4 preform on non-English national medical licensing examination? An evaluation in Chinese language.

ChatGPT, an artificial intelligence (AI) system powered by large-scale language models, has garnered significant interest in healthcare. Its performance dependent on the quality and quantity of training data available for a specific language, with the majority of it being in English. Therefore, its effectiveness in processing the Chinese language, which has fewer data available, warrants further investigation. This study aims to assess the of ChatGPT's ability in medical education and clinical decision-making within the Chinese context. We utilized a dataset from the Chinese National Medical Licensing Examination (NMLE) to assess ChatGPT-4's proficiency in medical knowledge in Chinese. Performance indicators, including score, accuracy, and concordance (confirmation of answers through explanation), were employed to evaluate ChatGPT's effectiveness in both original and encoded medical questions. Additionally, we translated the original Chinese questions into English to explore potential avenues for improvement. ChatGPT scored 442/600 for original questions in Chinese, surpassing the passing threshold of 360/600. However, ChatGPT demonstrated reduced accuracy in addressing open-ended questions, with an overall accuracy rate of 47.7%. Despite this, ChatGPT displayed commendable consistency, achieving a 75% concordance rate across all case analysis questions. Moreover, translating Chinese case analysis questions into English yielded only marginal improvements in ChatGPT's performance (p = 0.728). ChatGPT exhibits remarkable precision and reliability when handling the NMLE in Chinese. Translation of NMLE questions from Chinese to English does not yield an improvement in ChatGPT's performance.

Succinylation proteomic analysis identified differentially expressed succinylation sites affecting porcine muscle fiber type function.

Muscle fiber type is a major factor in pork meat quality, however, the role of post-translational protein modifications, especially succinylation, in the regulation of muscle fiber type is not fully understood. Here we performed protein succinylation profiles of fast-type biceps femoris (BF) and slow-type soleus (SOL) muscles. A total of 4,221 succinylation sites were identified from these samples, of which 294 sites were differentially expressed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that these succinylated proteins were mainly involved in glycolysis, tricarboxylic acid cycle, and fatty acid metabolism. Succinylation modification of the CRAT and RAB10 proteins was verified by co-immunoprecipitation. Protein-protein interaction (PPI) network analysis unveiled the interactions of these succinylated proteins that regulate pig myofiber type conversion. This investigation offers fresh perspectives into the molecular roles of protein succinylation in the regulation of pig myofiber type transformation and meat quality.

High-efficient subwavelength structure engineered grating couplers for 2-µm waveband high-speed data transmission.

The 2-µm waveband is becoming an emerging window for next-generation high-speed optical communication. To enable on-chip high-speed data transmission, improving the signal-to-noise ratio (SNR) by suppressing the coupling loss of a silicon chip is critical. Here, we report grating couplers for TE and TM polarized light at the 2-µm waveband. With a single-step fully etched process on the 340 nm silicon-on-insulator (SOI) platform, the devices experimentally demonstrate high coupling efficiency of -4.0 dB and 1-dB bandwidth of 70 nm for the TE polarized light, while -4.5 dB coupling efficiency and 58 nm 1-dB bandwidth for the TM polarized light. For comprehensive performance, both of them are among the best grating couplers operating in the 2-µm waveband so far. We also demonstrate 81Gbps high-speed on-chip data transmission using pulse amplitude modulation 8-level (PAM-8) signals.

Multi-band all-silicon TM-pass polarizer based on one-dimensional photonic crystals nanohole array.

We propose an on-chip transverse magnetic (TM)-pass polarizer utilizing one-dimensional photonic crystals for multi-band operation. The TE0 modes in the 1550/2000nm wave band are suppressed by carefully selecting the pitch lengths of the nanoholes, leveraging the bandgap of the nanohole array. Conversely, the TM0 modes remain almost unaffected. The TM-pass polarizer employs a single-etched design on a standard 220 nm SOI platform and has a compact length of ∼ 17.9 µm. The simulated bandwidths (BWs) for polarization extinction ratios (PERs) > 20 dB and > 25 dB are about 210 nm and 195 nm for the 1550 nm wave band, and 265 nm and 240 nm for the 2000nm wave band. Moreover, the insertion losses (ILs) are ∼ 0.5/0.3 dB at wavelengths of 1550/2000nm, respectively. For the fabricated device, the measured BWs for PER > 20 dB and > 25 dB are evaluated to be larger than 100 nm for both 1550/2000nm wave bands. The measured ILs are 1/0.8 dB at wavelengths of 1550/2000nm. This straightforward and compatible design opens possibilities for the development of practical multi-band silicon photonic integrated circuits.

Effects of Lactobacillus plantarum and Weissella viridescens on the Gut Microbiota and Serum Metabolites of Mice with Antibiotic-Associated Diarrhea.

Antibiotic-associated diarrhea (AAD) refers to diarrhea caused by gut microbiota disorders after the use of antibiotics, which seriously threatens the health of humans and animals. Therefore, it is necessary to find an effective therapy to treat AAD. This research aimed to explore the effects of Lactobacillus plantarum H-6 (L. plantarum H-6) and Weissella viridescens J-1 (W. viridescens J-1) on alleviating antibiotic-associated diarrhea induced by lincomycin hydrochloride (LH) in mice. The results show that L. plantarum H-6 could significantly reduce the expression of pro-inflammatory factors such as IL-1ß and IL-6 in colon tissue. At the same time, L. plantarum H-6 significantly increased the abundance of Lactobacillus and Akkermansia, decreased the abundance of Bacteroides, and increased the contents of L-tryptophan, LysoPC (20:4 (8Z, 11Z, 14Z, 17Z)), reduced riboflavin, threoninyl-methionine, and N-palmitoyl in serum. However, W. viridescens J-1 had little effect on the treatment of AAD. It can be concluded that L. plantarum H-6 can regulate mice's colonic microbial composition, improve their serum metabolic process, and alleviate antibiotic-associated diarrhea. This research may provide a novel therapeutic option for AAD.

Measurement of spin-lattice relaxation times in multiphase polymer systems.

Solid-state Nuclear Magnetic Resonance (NMR) has emerged as a pivotal technique for unraveling the microstructure and dynamics of intricate polymer and biological materials. Within this context, site-specific proton spin-lattice relaxation times in the laboratory frame (T1) and rotating frame (T1ρ) have become indispensable tools for investigating phase separation structures and molecular dynamics in multiphase polymer systems. Notably, the site-specific measurement of proton T1 and T1ρ is usually achieved via 13C detection in polymers, where 1H polarization is typically transferred to 13C via cross polarization (CP). Nevertheless, CP relies on the 1H-13C heteronuclear dipolar couplings, and thus it does not work well for the mobile components. In this study, via the integration of CP and RINEPT (refocused insensitive nuclei enhanced by polarization transfer), we propose a robust approach for the measurement of site-specific proton T1 and T1ρ in multiphase polymers. It overcomes the limitation of CP on transferring 1H polarization to 13C in mobile components, and thus enables simultaneous determination of site-specific proton T1 and T1ρ in rigid and mobile components in multiphase polymers in a single experiment. Such experiment can also be used for dynamics-based spectral editing due to the dynamic selectivity of CP- and RINEPT-based polarization transfer process. The proposed experiments are well demonstrated on three typical multiphase polymer systems, poly(methyl methacrylate)/polybutadiene (PMMA/PB) polymer blend, polyurethane (PU) and polystyrene-polybutadiene-polystyrene (SBS) elastomers. We envisage the proposed experiments can be a universal avenue for structural and dynamic elucidation of multiphase polymers containing both rigid and mobile components.

Identification of a basement membrane-related genes signature with immune correlation in bladder urothelial carcinoma and verification in vitro.

BACKGROUND: Bladder urothelial carcinoma (BLCA) is the most common genitourinary cancer and the prognosis of patients is often poor. However, studies of basement membrane-related genes (BM-related genes) in BLCA are less reported. Therefore, we established a BM-related genes signature to explore their functional and prognostic value in BLCA. METHODS: In this study, a BM-related genes signature was constructed by LASSO-Cox regression analysis, and then a series of bioinformatics methods was used to assess the accuracy and validity of the signature. We constructed a nomogram for clinical application and also screened for possible therapeutic drugs. To investigate the functions and pathways affected by BM-related genes in BLCA, we performed functional enrichment analyses. In addition, we analyzed the immune cell infiltration landscape and immune checkpoint-related genes in the high and low-risk groups. Finally, we confirmed the prognostic value of BM-related genes in BLCA in vitro. RESULTS: Combining multiple bioinformatics approaches, we identified a seven-gene signature. The accuracy and validity of this signature in predicting BLCA patients were confirmed by the test cohort. In addition, the risk score was strongly correlated with prognosis, immune checkpoint genes, drug sensitivity, and immune cell infiltration landscape. The risk score is an independent prognostic factor for BLCA patients. Further experiments revealed that all seven signature genes were differentially expressed between BLCA cell lines and normal bladder cells. Finally, overexpression of LAMA2 inhibited the migration and invasion ability of BLCA cell lines. CONCLUSIONS: In summary, the BM-related genes signature was able to predict the prognosis of BLCA patients accurately, indicating that the BM-related genes possess great clinical value in the diagnosis and treatment of BLCA. Moreover, LAMA2 could be a potential therapeutic target, which provides new insights into the application of the BM-related genes in BLCA patients.

Development and Validation of a UHPLC-MS/MS Method for the Quantification of a Novel PYGB Inhibitor in Plasma: Application to Pharmacokinetic Studies.

In previous studies, we reported compound 1 (5-chloro-N-(4-oxo-2,2-dipropyl-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-yl)-1H-indole-2-carboxamide) as a novel PYGB inhibitor, and found that it had better anti-ischemic brain injury activity. In this study, we established and validated a novel UHPLC-MS/MS method for the quantitative determination of compound 1 in plasma, then applied the method to study the pharmacokinetic parameters and brain tissue distribution of compound 1 in SD (Sprague-Dawley) rats after intravenous administration. The experimental results showed that the method met the validation requirements set by the US FDA in terms of linearity, accuracy, precision, and stability. The validated method was then used for pharmacokinetic studies in rat plasma, and it was found that compound 1 exhibited linear pharmacokinetic characteristics when administered in the dose range of 0.8-3.2 mg/kg. Finally, we also conducted a brief preliminary investigation of the brain tissue distribution of compound 1 in rats after injection and found that the brain tissue concentrations at 0.25 h and 2 h of administration were 440 ± 19.1 ng/kg and 111 ± 23.9 ng/kg, respectively. Additionally, the CBrain/CPlasma ratio was 0.112 ± 0.0185 and 0.112 ± 0.0292, respectively. These results indicated that compound 1 was able to cross the blood-brain barrier. This study provides important support for the application of compound 1 in ischemic brain injury diseases.

Discovery of novel 2,3,4,5-tetrahydrospiro[benzo[c]azepine-1,1'-cyclohexan]-5-ol derivatives as PARP-1 inhibitors.

As an essential marker of cancer treatment, PARP-1 inhibitors could effectively kill tumor cells through a mechanism known as synthetic lethality and are used to treat a variety of cancers. In order to explore novel PARP-1 inhibitors, a series of 22 novel erythrina derivatives were reported and preliminarily explored their mechanism of action. The antitumor activities against four human cancer cell lines including A549, OVCAR-3, HCT-116, and MCF-7 were evaluated, and the preliminary SARs were summarized. Among them, compound 11b exhibited better anti-proliferative effects against A549 cells (IC50 = 1.95 µM). The SI results showed that compound 11b had low toxicity. Moreover, compound 11b displayed excellent PARP-1 inhibitory activities with IC50 values of 19.24 nM. In addition, molecular docking studies provided the rational binding modes of compound 11b in complexes with PARP-1. The flow cytometry assays revealed that compound 11b could induce apoptosis of A549 cells (P < 0.001). Simultaneously, compound 11b could effectively reduce the formation of PAR (P < 0.001). The ADMET prediction results indicated compound 11b had similar properties to rucaparib. Collectively, compound 11b has potential research value for further investigation.

High-speed mid-infrared graphene electro-optical modulator based on suspended germanium slot waveguides.

The mid-infrared (MIR) region is attracting increasing interest for on-chip synchronous detection and free-space optical (FSO) communications. For such applications, a high-performance electro-optical modulator is a crucial component. In this regard, we propose and investigate a graphene-based electro-absorption modulator (EAM) and microring modulator (MRM) using the suspended germanium waveguide platform. The modulators are designed for the second atmospheric window (8 to 12 µm). The incorporation of double-layer graphene on the suspended slot waveguide structure allows for the significant enhancement of light-graphene interaction, theoretically achieving a 3-dB bandwidth as high as 78 GHz. The EAM shows a calculated modulation depth of 0.022-0.045 dB/µm for the whole operation wavelength range. The MRM exhibits a calculated extinction ratio as high as 68.9 dB and a modulation efficiency of 0.59 V·cm around 9 µm. These modulators hold promise for constructing high-speed FSO communication and on-chip spectroscopic detection systems in the MIR atmospheric window.

Clinical Outcomes with GLP-1 Receptor Agonists in Patients with Heart Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, there remains uncertainty about the efficiency of GLP-1 RAs in patients with heart failure (HF). METHODS: Randomized placebo-controlled trials (RCTs) that reported the effect of GLP-1 RAs on prognosis in patients with HF were identified by searching databases. The primary outcome was defined as MACE. Trail Sequential Analysis (TSA) was used to evaluate the reality and authenticity. RESULTS: Nine RCTs involving 8920 patients with HF were included. GLP-1 RAs significantly reduced the risk of MACE compared with placebo (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.77-0.98) in HF coexisting with T2DM. The benefit was not observed in all-cause death (HR 0.99, 95% CI 0.84-1.15), hospitalization for heart failure (HR 1.04, 95% CI 0.89-1.22), cardiovascular death (HR 0.95, 95% CI 0.79-1.16), myocardial infarction (HR 0.88, 95% CI 0.71-1.08), stroke (HR 1.03, 95% CI 0.75-1.43) and death or hospitalization for HF (HR 1.07, 95% CI 0.78-1.46). GLP-1 RAs did not improve the change in LVEF (mean difference [MD]): - 0.86, p = 0.12, left-ventricular end-diastolic volume (LVEDV) (MD: 3.54, p = 0.11), left-ventricular end-systolic volume (LVESV) (MD: 2.78, p = 0.07) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (MD: - 140.36, p = 0.08). However, GLP-1 RAs significantly increased the change in the 6-min walk test (MWT) distance (MD: 19.74, p = 0.002). In the subgroup analyses, human GLP-1 RAs, but not nonhuman GLP-1 RAs, reduced the risk of MACE in patients with HF (p interaction = 0.11). Grading of Recommendations Assessment, Development and Evaluation (GRADE) showed moderate certainty for MACE, all-cause death and hospitalization for HF. Trail Sequential Analysis revealed that there may be a high possibility of false positive results for MACE. CONCLUSION: Compared with placebo, GLP-1 RAs may reduce the risk of MACE in patients with HF coexisting with T2DM, with a more significant efficiency of human GLP-1 RAs. More RCTs are needed to assess the cardiovascular benefits of GLP-1 RAs in HF, regardless of T2DM. REGISTRATION: The protocol for this meta-analysis is registered on PROSPERO [CRD42022357886].