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.

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.

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.

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.

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.

Association between triglyceride glucose index and arterial stiffness and coronary artery calcification: a systematic review and exposure-effect meta-analysis.

BACKGROUND: The triglyceride and glucose (TyG) index has been linked to various cardiovascular diseases. However, it's still unclear whether the TyG index is associated with arterial stiffness and coronary artery calcification (CAC). METHODS: We conducted a systematic review and meta-analysis of relevant studies until September 2022 in the PubMed, Cochrane Library, and Embase databases. We used a random-effects model to calculate the pooled effect estimate and the robust error meta-regression method to summarize the exposure-effect relationship. RESULTS: Twenty-six observational studies involving 87,307 participants were included. In the category analysis, the TyG index was associated with the risk of arterial stiffness (odds ratio [OR]: 1.83; 95% CI 1.55-2.17, I2 = 68%) and CAC (OR: 1.66; 95% CI 1.51-1.82, I2 = 0). The per 1-unit increment in the TyG index was also associated with an increased risk of arterial stiffness (OR: 1.51, 95% CI 1.35-1.69, I2 = 82%) and CAC (OR: 1.73, 95% CI 1.36-2.20, I2 = 51%). Moreover, a higher TyG index was shown to be a risk factor for the progression of CAC (OR = 1.66, 95% CI 1.21-2.27, I2 = 0, in category analysis, OR = 1.47, 95% CI 1.29-1.68, I2 = 41% in continuity analysis). There was a positive nonlinear association between the TyG index and the risk of arterial stiffness (Pnonlinearity < 0.001). CONCLUSION: An elevated TyG index is associated with an increased risk of arterial stiffness and CAC. Prospective studies are needed to assess causality.

Silicon MMI-based power splitter for multi-band operation at the 1.55 and 2†µm wave bands.

Multimode interference (MMI)-based power splitters are fundamental building blocks for integrated photonic devices consisting of an interferometer structure. In order to forestall the 'capacity crunch' in optical communications, integrated devices capable of operating in multiple spectral bands (e.g., the conventional telecom window and the emerging 2 µm wave band) have been proposed and are attracting increasing interest. Here, we demonstrate for the first time, to the best of our knowledge, the realization of a dual-band MMI-based 3 dB power splitter operating at the 1.55 and 2 µm wave bands. The fabricated power splitter exhibits low excess losses of 0.21 dB and 0.32 dB with 1 dB bandwidths for 1500-1600 nm and 1979-2050 nm, respectively.

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.

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.

Glycated albumin and risk of cardiovascular diseases and mortality in patients with and without dialysis: A meta-analysis.

BACKGROUND: Several studies have shown that glycated albumin (GA) is a more accurate measure of short-term blood sugar control in patients with dialysis. We aim to investigate the relationship between GA and the risk of cardiovascular diseases (CVDs) and mortality in patients both with and without dialysis. MATERIALS AND METHODS: We searched cohort studies of associations between GA level and CVD and mortality in PubMed, Cochrane Library and Embase databases. The effect size was summarized by the random effects model, and the dose-response association was determined by robust error meta-regression method. RESULTS: This meta-analysis included data from 80 024 participants in 17 cohort studies, 12 of which were prospective and five were retrospective. The results showed that higher levels of GA were associated with increased risk of CV mortality [hazard ratio = 1.90; 95% confidence interval (CI) 1.22-2.98], all-cause mortality (hazard ratio = 1.64; 95% CI 1.41-1.90), major adverse cardio-cerebral events (risk ratio = 1.41; 95% CI 1.17-1.71), coronary artery disease (odds ratio = 2.24; 95% CI 1.75-2.86) and stroke (risk ratio = 1.72; 95% CI 1.24-2.38). The dose-response analysis showed that GA levels were positively and linearly associated with the risk of CV mortality (p = .38), all-cause mortality (p = .57) and coronary artery disease (p = .18). Subgroup analysis showed that high levels of GA were associated with the risk of CV and all-cause mortality, regardless of dialysis status, with significant differences between subgroups of dialysis (CV mortality: p = .02; all-cause mortality: p = .03). CONCLUSION: High GA levels are associated with an increased risk of CVDs and mortality, regardless of dialysis status.

Responses of soil phosphorus cycling and bioavailability to plant invasion in river-lake ecotones.

The invasion of exotic plants in the river-lake ecotone has seriously affected the nutrient cycling processes in wetland soil. The South American species Alternanthera philoxeroides (Mart.) Griseb. is rapidly invading the river-lake ecotone in subtropical China, and has become the dominant species in the river-lake ecotone. However, there have been few studies on the effects of A. philoxeroides invasion on soil phosphorus (P) cycling and bioavailability in this ecotone. Here, we measured the bioavailable P fractions, physicochemical properties and nutrient content in the surface soils of the native plant (Zizania latifolia (Griseb.) Turcz and Nelumbo nucifera Gaertn.) communities and the adjacent invasive A. philoxeroides communities in three river-lake ecotones with different nutrient substrates in the subtropical Dongting Lake basin over a 3-year period to reveal the effects of A. philoxeroides invasion on the morphology and concentrations of soil bioavailable P. The principal coordinate analysis results showed that the A. philoxeroides invasion significantly altered the bioavailable P concentrations in the soil of native plant communities in the different river-lake ecotones, and this effect was not disturbed by the heterogeneity of the soil matrix. However, the effects of invasion into different native plant communities on the fractions of soil bioavailable P were different. Compared with native Z. latifolia and N. nucifera communities, A. philoxeroides invasion increased the concentration of inorganic P by 39.5% and 3.7%, respectively, and the concentration of organic P decreased by 32.7% and 31.9%, respectively. In addition, the invasion promoted P cycling and accumulation in the river-lake ecotone, which resulted in average decreases in the soil N:P and C:P ratios of 7.9% and 12.5%, respectively. These results highlight the impact of exotic plant invasions on nutrient cycling in wetland ecosystems in the river-lake ecotone, and this process may be detrimental to the late recovery of native plants.

A comprehensive assessment of runoff dynamics in response to climate change and human activities in a typical karst watershed, southwest China.

The Chengbi River Basin is a typical karst watershed in Southwest China. Understanding the effects of climate change (CC) and human activities (HAs) on hydrological process is important for regional water resources management and water security. However, a comprehensive assessment of the effects of CC and HAs on runoff dynamics at different time scales in the Chengbi River Basin is still lacking. To address these needs, we used Budyko Mezentsev-Choudhurdy-Yang and Slope change ratio of accumulative quantity methods to assess the contribution of the changing environment to annual and intra-annual runoff changes in the Chengbi River Basin. The results indicated that annual runoff time series was divided into the base phase Ta (1980-1996) and the change phase Tb (1997-2019). Compared to the natural status in Ta, the relative contributions of CC and HAs to the runoff increase in Tb were 154.86% and -54.86%. In addition, the shift in intra-annual runoff occurred in 2007 and was mainly caused by HAs, with a contribution rate of 76.22%. The increase in annual runoff in Tb could be attributed to the positive contribution of rainfall. Changes in rainfall and reservoir construction altered the original state of intra-annual runoff. Furthermore, the high degree of heterogeneity in the surface karst zone increased the runoff coefficient. The spatial unsaturation of the subsurface water-bearing media and rainfall patterns caused a significant lag effect in the response of surface runoff to rainfall. This study can help researchers and policy makers to better understand the response of karst runoff to changing environment and provide insights for future water resources management and flood control measures.

Computational Insights into Novel Inhibitor N-(3-(tert-Butylcarbamoyl)-4-methoxyphenyl)-indole and Ingliforib Specific against GP Isoenzyme Dimers Interaction Mechanism.

The high conservation of the three subtypes of glycogen phosphorylase (GP) presents significant challenges for specific inhibitor studies targeting GP. Our prior screening revealed that compound 1 exhibited unequal inhibitory activity against the three GP subtypes, with a noticeable effect against brain GP (PYGB). The commercially available ingliforib demonstrated potent inhibitory activity specifically against liver GP (PYGL). To guide the further design and screening of high-specificity inhibitors, the possible reasons for the differential inhibitory activity of two compounds against different GP subtypes were analyzed, with ingliforib as a reference, through molecular docking and molecular dynamics simulations. Initially, the study predicted the binding modes of ligands with the three GP receptor subtypes using molecular docking. Subsequently, this was validated by molecular dynamics experiments, and possible amino acid residues that had important interactions were explored. The strong correlation between the calculated interaction free energies and experimental inhibitory activity implied the reasonable binding conformations of the compounds. These findings offer insight into the different inhibitory activity of compound 1 and ingliforib against all three GP subtypes and provide guidance for the design of specific target molecules that regulate subtype selectivity.

A Novel 5-Chloro-N-phenyl-1H-indole-2-carboxamide Derivative as Brain-Type Glycogen Phosphorylase Inhibitor: Validation of Target PYGB.

Brain-type glycogen phosphorylase (PYGB) inhibitors are recognized as prospective drugs for treating ischemic brain injury. We previously reported compound 1 as a novel glycogen phosphorylase inhibitor with brain-protective properties. In this study, we validated whether PYGB could be used as the therapeutic target for hypoxic-ischemic diseases and investigated whether compound 1 exerts a protective effect against astrocyte hypoxia/reoxygenation (H/R) injury by targeting PYGB. A gene-silencing strategy was initially applied to downregulate PYGB proteins in mouse astrocytes, which was followed by a series of cellular experiments with compound 1. Next, we compared relevant indicators that could prove the protective effect of compound 1 on brain injury, finding that after PYGB knockdown, compound 1 could not obviously alleviate astrocytes H/R injury, as evidenced by cell viability, which was not significantly improved, and lactate dehydrogenase (LDH) leakage rate, intracellular glucose content, and post-ischemic reactive oxygen species (ROS) level, which were not remarkably reduced. At the same time, cellular energy metabolism did not improve, and the degree of extracellular acidification was not downregulated after administration of compound 1 after PYGB knockdown. In addition, it could neither significantly increase the level of mitochondrial aerobic energy metabolism nor inhibit the expression of apoptosis-associated proteins. The above results indicate that compound 1 could target PYGB to exert its protective effect against cellular H/R injury in mouse astrocytes. Simultaneously, we further demonstrated that PYGB could be an efficient therapeutic target for ischemic-hypoxic diseases. This study provides a new reference for further in-depth study of the action mechanism of the efficacy of compound 1.

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.

Silicon photonic flat-top WDM (de)multiplexer based on cascaded Mach-Zehnder interferometers for the 2†µm wavelength band: publisher's note.

This publisher's note contains a correction to [Opt. Express30, 28232 (2022)10.1364/OE.467473].

Silicon photonic flat-top WDM (de)multiplexer based on cascaded Mach-Zehnder interferometers for the 2 µm wavelength band.

The 2 µm wavelength band has proven to be a promising candidate for the next communication window. Wavelength-division multiplexing (WDM) transmission at 2 µm can greatly increase the capacity of optical communication systems. Here, we experimentally demonstrate a high-performance silicon photonic flat-top 8-channel WDM (de)multiplexer based on cascaded Mach-Zehnder interferometers for the 2 µm wavelength band. A three-stage-coupler scheme is utilized to provide passbands and reduce channel crosstalk, and 11 thermo-optic phase shifters have allowed active compensation of waveguide phase errors. The fabricated device shows low insertion loss (< 0.9 dB), channel crosstalk (< 20.6 dB) and 1-dB bandwidth of 2.3 nm for operating wavelength ranging from 1955nm to 1985nm. The demonstrated (de)multiplexer could potentially be used for WDM optical data communication in the 2 µm spectral band.

Liver fibrosis scores and prognosis in patients with cardiovascular diseases: A systematic review and meta-analysis.

BACKGROUND: In patients with nonalcoholic fatty liver disease, liver fibrosis was associated with a higher risk of cardiovascular events. However, the relationship between liver fibrosis scores and clinical outcomes in patients with cardiovascular disease remains unclear. METHODS: Searching from PubMed, EMBASE and Cochrane Library databases yielded cohort studies that reported adjusted effect size between liver fibrosis scores (Fibrosis-4 score [FIB-4] or NAFLD fibrosis score [NFS]) and prognosis in patients with cardiovascular disease. The effect size was computed using a random-effects model. RESULTS: This meta-analysis included twelve cohort studies involving 25,252 patients with cardiovascular disease. Participants with the highest baseline level of FIB-4 or NFS had a significantly increased risk of cardiovascular events (FIB-4, HR: 1.75, 95% CI: 1.53-2.00, I 2  = 0%; NFS, HR: 1.92, 95% CI: 1.50-2.47, I 2  = 47%). This finding was consistent with the analysis of FIB-4 or NFS as a continuous variable (per 1-unit increment FIB-4, HR: 1.15, 95% CI: 1.06-1.24, I 2  = 72%; NFS, HR: 1.15, 95% CI: 1.07-1.24, I 2  = 71%). Furthermore, participants with the highest levels of FIB-4 or NFS had a greater risk of cardiovascular mortality (FIB-4, HR: 2.07, 95% CI: 1.19-3.61, I 2  = 89%; NFS, HR: 3.72, 95% CI: 2.62-5.29, I 2  = 60%) and all-cause mortality (FIB-4, HR: 1.81, 95% CI: 1.24-2.66, I 2  = 90%; NFS, HR: 3.49, 95% CI: 2.82-4.31, I 2  = 25%). This result was also consistent as a continuous variable. CONCLUSION: Higher levels of FIB-4 and NFS are related to an increased risk of cardiovascular events, cardiovascular mortality and all-cause mortality in patients with cardiovascular disease.

Single-step etched two-dimensional polarization splitting dual-band grating coupler for wavelength (de)multiplexing.

Diffractive periodic-structure-based grating couplers (GCs) are the most widely used devices for light coupling between optical fibers and integrated photonic devices. However, conventional GCs have limited wavelength operation and are polarization specific, which is due to the intrinsic radiation angle dependency on both wavelength and polarization. Here we propose and experimentally demonstrate a polarization-splitting dual-band grating coupler (PS-DBGC) for polarization diversity and wavelength division (de)multiplexing (WDM) operation. The four-port two-dimensional PS-DBGC is based on a periodically arranged structure with square holes, and requires only a single etch step in a 340-nm silicon-on-insulator platform. The simulation predicts that the maximum coupling efficiency (CE) of the proposed PS-DBGC is -2.8 dB and -4.6 dB for the O- and C-band, respectively. The measured peak CEs of the fabricated device are -4.7 dB at 1280 nm and -8.4 dB at 1522 nm. We anticipate that this PS-DBGC could potentially improve the performance of any future integrated WDM passive optical network.