Pazopanib attenuated bleomycin-induced pulmonary fibrosis via suppressing TGF-ß1 signaling pathway.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a high mortality rate and limited treatment efficacy. Nintedanib, a tyrosine kinase inhibitor, is clinically used to treat pulmonary fibrosis. At present, only nintedanib is on the market for the treatment of pulmonary fibrosis. Pazopanib is a drug for the treatment of renal cell carcinoma and advanced soft tissue sarcoma. Methods: In this study, we explored whether pazopanib can attenuate bleomycin (BLM)-induced pulmonary fibrosis and explored its antifibrotic mechanism. In vivo and in vitro investigations were carried out to investigate the efficacy and mechanism of action of pazopanib in pulmonary fibrosis. Results: In vivo experiments showed that pazopanib can alleviate pulmonary fibrosis caused by BLM, reduce the degree of collagen deposition and improve lung function. In vitro experiments showed that pazopanib suppressed transforming growth factor-ß1 (TGF-ß1)-induced myofibroblast activation and promoted apoptosis and autophagy in myofibroblasts. Further mechanistic studies demonstrated that pazopanib inhibited the TGF-ß1/Smad and non-Smad signaling pathways during fibroblast activation. Conclusions: In conclusion, pazopanib attenuated BLM-induced pulmonary fibrosis by suppressing the TGF-ß1 signaling pathway. Pazopanib inhibits myofibroblast activation, migration, autophagy, apoptosis, and extracellular matrix (ECM) buildup by downregulating the TGF-ß1/Smad signal route and the TGF-ß1/non-Smad signal pathway. It has the same target as nintedanib and is a tyrosine kinase inhibitor.

Nonlinear optical diode effect in a magnetic Weyl semimetal.

Diode effects are of great interest for both fundamental physics and modern technologies. Electrical diode effects (nonreciprocal transport) have been observed in Weyl systems. Optical diode effects arising from the Weyl fermions have been theoretically considered but not probed experimentally. Here, we report the observation of a nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetization introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). We demonstrate a six-fold change of the measured SHG intensity between opposite propagation directions over a bandwidth exceeding 250 meV. Supported by density-functional theory, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of this broadband effect. We further demonstrate current-induced magnetization switching and thus electrical control of the NODE. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials and further opens new pathways for the unidirectional manipulation of light.

Correlated order at the tipping point in the kagome metal CsV3Sb5.

Spontaneously broken symmetries are at the heart of many phenomena of quantum matter and physics more generally. However, determining the exact symmetries that are broken can be challenging due to imperfections such as strain, in particular when multiple electronic orders are competing. This is exemplified by charge order in some kagome systems, where evidence of nematicity and flux order from orbital currents remains inconclusive due to contradictory measurements. Here we clarify this controversy by fabricating highly symmetric samples of a member of this family, CsV3Sb5, and measuring their transport properties. We find that a measurable anisotropy is absent at any temperature in the unperturbed material. However, a pronounced in-plane transport anisotropy appears when either weak magnetic fields or strains are present. A symmetry analysis indicates that a perpendicular magnetic field can indeed lead to in-plane anisotropy by inducing a flux order coexisting with more conventional bond order. Our results provide a unifying picture for the controversial charge order in kagome metals and highlight the need for materials control at the microscopic scale in the identification of broken symmetries.

Wavelength-tunable spatiotemporal mode-locking in a large-mode-area Er:ZBLAN fiber laser at 2.8†µm.

We report a tunable spatiotemporally mode-locked large-mode-area Er:ZBLAN fiber laser based on the nonlinear polarization rotation technique. A diffraction grating is introduced to select the operating wavelength. Under the spectral and spatial filtering effects provided by the grating and spatial coupling respectively, stable ps-level spatiotemporally mode-locked pulses around 2.8 µm with a repetition rate of 43.4 MHz are generated. Through a careful adjustment of the grating, a broad wavelength tuning range from 2747 to 2797 nm is realized. To the best of our knowledge, this is the first wavelength-tunable spatiotemporally mode-locked fiber laser in the mid-infrared region.

Thioglucose-derived tetrasulfide, a unique polysulfide model compound.

Polysulfides have received increased interest in redox biology due to their role as the precursors of H2S and persulfides. However, the compounds that are suitable for biological investigations are limited to cysteine- and glutathione-derived polysulfides. In this work, we report the preparation and evaluation of a novel polysulfide derived from thioglucose, which represents the first carbohydrate-based polysulfide. This compound, thioglucose tetrasulfide (TGS4), showed excellent stability and water solubility. H2S and persulfide production from TGS4, as well as its associated antioxidative property were also demonstrated. Additionally, TGS4 was demonstrated to significantly induce cellular sulfane sulfur level increase, in particular for the formation of hydropersulfides/trisulfides. These results suggest that TGS4 is a useful tool for polysulfide research.

Impact of heat on emergency hospital admissions related to kidney diseases in Texas: Uncovering racial disparities.

BACKGROUND AND OBJECTIVE: While impact of heat exposure on human health is well-documented, limited research exists on its effect on kidney disease hospital admissions especially in Texas, a state with diverse demographics and a high heat-related death rate. We aimed to explore the link between high temperatures and emergency kidney disease hospital admissions across 12 Texas Metropolitan Statistical Areas (MSAs) from 2004 to 2013, considering causes, age groups, and ethnic populations. METHODS: To investigate the correlation between high temperatures and emergency hospital admissions, we utilized MSA-level hospital admission and weather data. We employed a Generalized Additive Model to calculate the association specific to each MSA, and then performed a random effects meta-analysis to estimate the overall correlation. Analyses were stratified by age groups, admission causes, and racial/ethnic disparities. Sensitivity analysis involved lag modifications and ozone inclusion in the model. RESULTS: Our analysis found that each 1 °C increase in temperature was associated with a 1.73 % (95 % CI [1.43, 2.03]) increase in hospital admissions related to all types of kidney diseases. Besides, the effect estimates varied across different age groups and specific types of kidney diseases. We observed statistically significant associations between high temperatures and emergency hospital admissions for Acute Kidney Injury (AKI) (3.34 % (95 % CI [2.86, 3.82])), Kidney Stone (1.76 % (95 % CI [0.94, 2.60])), and Urinary Tract Infections (UTI) (1.06 % (95 % CI [0.61, 1.51])). Our research findings indicate disparities in certain Metropolitan Statistical Areas (MSAs). In Austin, Houston, San Antonio, and Dallas metropolitan areas, the estimated effects are more pronounced for African Americans when compared to the White population. Additionally, in Dallas, Houston, El Paso, and San Antonio, the estimated effects are greater for the Hispanic group compared to the Non-Hispanic group. CONCLUSIONS: This study finds a strong link between higher temperatures and kidney disease-related hospital admissions in Texas, especially for AKI. Public health actions are necessary to address these temperature-related health risks, including targeted kidney health initiatives. More research is needed to understand the mechanisms and address health disparities among racial/ethnic groups.

Soliton rain in all-polarization-maintaining mode locked fiber laser.

For the first time the phenomenon of soliton rain is observed in a mode-locked fiber laser with all-polarization-maintaining (all-PM) architecture. The laser is mode-locked using a semiconductor saturable absorber mirror (SESAM) and operates in the all-normal dispersion (ANDi) regime. The operation state of the laser can be switched from dissipative soliton to soliton rain by simply raising the pump power, without any manipulation of the intracavity polarization state given that all components of the resonator are made of PM fibers. The soliton rain generated in the laser is self-starting and replicable, since it occurs in every individual operation of the laser as the pump power is increased to an approximately invariant value.

Bioinspired soft robots for deep-sea exploration.

The deep ocean, Earth's untouched expanse, presents immense challenges for exploration due to its extreme pressure, temperature, and darkness. Unlike traditional marine robots that require specialized metallic vessels for protection, deep-sea species thrive without such cumbersome pressure-resistant designs. Their pressure-adaptive forms, unique propulsion methods, and advanced senses have inspired innovation in designing lightweight, compact soft machines. This perspective addresses challenges, recent strides, and design strategies for bioinspired deep-sea soft robots. Drawing from abyssal life, it explores the actuation, sensing, power, and pressure resilience of multifunctional deep-sea soft robots, offering game-changing solutions for profound exploration and operation in harsh conditions.

Highly efficient octave-spanning long-wavelength infrared generation with a 74% quantum efficiency in a χ(2) waveguide.

The realization of compact and efficient broadband mid-infrared (MIR) lasers has enormous impacts in promoting MIR spectroscopy for various important applications. A number of well-designed waveguide platforms have been demonstrated for MIR supercontinuum and frequency comb generations based on cubic nonlinearities, but unfortunately third-order nonlinear response is inherently weak. Here, we propose and demonstrate for the first time a χ(2) micrometer waveguide platform based on birefringence phase matching for long-wavelength infrared (LWIR) laser generation with a high quantum efficiency. In a ZnGeP2-based waveguide platform, an octave-spanning spectrum covering 5-11 µm is generated through optical parametric generation (OPG). A quantum conversion efficiency of 74% as a new record in LWIR single-pass parametric processes is achieved. The threshold energy is measured as ~616 pJ, reduced by more than 1-order of magnitude as compared to those of MIR OPGs in bulk media. Our prototype micro-waveguide platform could be extended to other χ(2) birefringence crystals and trigger new frontiers of MIR integrated nonlinear photonics.

An integrated investigation of 16S rRNA gene sequencing and proteomics to elucidate the mechanism of Corydalis bungeana Turcz. on dextran sulfate sodium-induced colitis.

Corydalis bungeana Turcz. (CBT) is frequently used to treat inflammatory illnesses, the mechanisms underlying its use to ulcerative colitis (UC) remain unclear. A dextran sulfate sodium (DSS)-induced UC mice model was established. The disease activity index (DAI), colonic length, histological inspection by hematoxylin-eosin staining, the cytokines levels in the colon, proteomics and intestinal flora in mice were investigated to evaluate the effect of CBT. The results showed that CBT can significantly reduce the DAI, increase the length of colon, improve the pathological injury of colon tissue, decrease the level of TNF-α, IL-6, IL-1ß and increase the level of IL-10 in UC mice. Gut microbe sequencing showed that CBT could enhance the abundance of the intestinal microbiome, decrease possibly harmful bacteria and promote potentially helpful microbes. Proteomics investigation showed that 20 overlapping differentially expressed proteins (DEPs) were discovered in the control, model, and CBT administration groups. The DEPs in the CBT administration group were connected to biological procedures mainly involving detoxification. Extracellular matrix (ECM) receptor-associated proteins such as Col6a1 and CD36 may be important targets for CBT treatment of UC. Overall, this integrated methodology identified a comprehensive multi-omics network, composed of a certain set of gut microbiota and proteins, which may be potential targets for CBT treatment with UC.

Product maturation and antibiotic resistance genes enrichment in food waste digestate and Chinese medicinal herbal residues co-composting.

The land application of food waste digestate (FWD) requires a composting process to improve its soil amendment performance and alleviate environmental risks. This study proposed co-composting of Chinese medicinal herbal residues (CMHRs) and FWD as a means to improve the maturation performance and investigated the evolution of antibiotic resistance genes (ARGs). Results demonstrated that CMHRs addition effectively accelerated the maturity of FWD composting to less than 35 days, remarkably removed its remaining antibiotics by 83.0% and promoted the formation of humification substances. However, both quantitative PCR and 16S rRNA sequencing analysis indicated that a significant enrichment of ARGs and mobile genetic elements including frA1, tetX, blaTEM, InuB-01, aadA2-02 and IntI-1 was observed via the co-composting of FWD and CMHRs. These results indicated that the land application of products obtained from FWD and CMHRs co-composting is at risk of spreading ARGs, although the composting process could be significantly improved.

A novel classifier combining G protein-coupled receptors and the tumor microenvironment is associated with survival status in glioblastoma.

Background: Numerous studies have highlighted the crucial role of G protein-coupled receptors (GPCRs) in tumor microenvironment (TME) remodeling and their correlation with tumor progression. However, the association between GPCRs and the TME in glioblastoma (GBM) remains largely unexplored. Methods: In this study, we investigated the expression profile of GPCRs in GBM using integrated data from single-cell RNA sequencing and bulk sequencing. Surgical samples obtained from meningioma and GBM patients underwent single-cell RNA sequencing to examine GPCR levels and cell-cell interactions. Tumor microenvironment (TME) score is calculated by the infiltrated immune cells with CIBERSORT. Results: Our findings revealed a predominantly increased expression of GPCRs in GBM, and demonstrated that the classification of GPCRs and TME is an independent risk factor in GBM. Patients with high GPCR expression in the tumor tissue and low TME score exhibited the worst outcomes, suggesting a potentially aggressive tumor phenotype. On the other hand, patients with low GPCR expression in the tumor tissue and high TME score showed significantly better outcomes, indicating a potentially more favorable tumor microenvironment. Furthermore, the study found that T cells with high GPCR levels displayed extensive cell-cell connections with other tumor and immune cells in the single cell RNA analysis, indicating their potential involvement in immune escape. Conclusion: In conclusion, GPCRs in combination with TME classification can serve as prognostic markers for GBM. GPCRs play an essential role in tumor progression and the TME in GBM.

Screen-Printing Technology for Scale Manufacturing of Perovskite Solar Cells.

As a key contender in the field of photovoltaics, third-generation thin-film perovskite solar cells (PSCs) have gained significant research and investment interest due to their superior power conversion efficiency (PCE) and great potential for large-scale production. For commercialization consideration, low-cost and scalable fabrication is of primary importance for PSCs, and the development of the applicable film-forming techniques that meet the above requirements plays a key role. Currently, large-area perovskite films are mainly produced by printing techniques, such as slot-die coating, inkjet printing, blade coating, and screen-printing. Among these techniques, screen printing offers a high degree of functional layer compatibility, pattern design flexibility, and large-scale ability, showing great promise. In this work, the advanced progress on applying screen-printing technology in fabricating PSCs from technique fundamentals to practical applications is presented. The fundamentals of screen-printing technique are introduced and the state-of-the-art studies on screen-printing different functional layers in PSCs and the control strategies to realize fully screen-printed PSCs are summarized. Moreover, the current challenges and opportunities faced by screen-printed perovskite devices are discussed. This work highlights the critical significance of high throughput screen-printing technology in accelerating the commercialization course of PSCs products.

Impact of heat on emergency hospital admission in Texas: geographic and racial/ethnic disparities.

BACKGROUND: Studies exploring the racial/ethnicity disparity of the impact of heat on hospital admission are notably limited, especially in Texas, a state with a diverse population and consistently ranking among the top ten U.S. states for heat-related deaths per capita from 2018 to 2020. OBJECTIVE: Our objective is to determine the correlation between elevated temperatures and emergency hospital admissions for various causes and age groups across 12 Metropolitan Statistical Areas(MSAs) in Texas. Additionally, we aim to investigate health inequalities in the five largest MSAs in Texas between 2004 and 2013. METHODS: We used MSA-level hospital admission and weather data to estimate the relationship between heat and emergency hospital admissions. We applied a Generalized Additive Model and random effects meta-analysis to calculate MSA-specific associations and overall correlation, repeating the analysis for age groups and specific causes of admission. We also investigated health disparities across racial and ethnic groups and performed a sensitivity analysis. RESULTS: The results showed that a 1 °C increase in temperature was associated with a 0.50% (95% CI [0.38%, 0.63%]) increase in all-cause emergency hospital admissions. Heat's impact on hospital admissions varied among age groups and causes, with children under 6 years showing the highest effect estimate (0.64% (95% CI [0.32%,0.96%])). Statistically significant associations were found for Cardiovascular Diseases (0.27% (95% CI [0.07%,0.47%])), Ischemic Heart Diseases (0.53% (95% CI [0.15%,0.92%])), Pneumonia (0.70% (95% CI [0.25%,1.16%])), and Respiratory Diseases (0.67% (95% CI [0.18%,1.17%])). Health disparities were found among racial and ethnic groups in the five largest MSAs. IMPACT STATEMENT: Studies exploring the impact of heat on hospital admission in Texas are notably limited. Our research provided a comprehensive examination of the connection between heat and emergency hospital admissions throughout Texas. Furthermore, we are the first to examine racial/ethnic disparities, identifying African American and Hispanic groups as disproportionately affected. These insights provide valuable insights for policymakers to allocate resources and implement strategies to mitigate the negative consequences of rising temperatures.

Two Individual Super-Bound State Modes within Band Gap with Ultra-High Q Factor for Potential Sensing Applications in the Terahertz Wave Band.

Bound states in the continuum (BICs) garnered significant research interest in the field of sensors due to their exceptionally high-quality factors. However, the wide-band continuum in BICs are noise to the bound states, and it is difficult to control and filter. Therefore, we constructed a top-bottom symmetric cavity containing three high permittivity rectangular columns. The cavity supports a symmetry-protected (SP) superbound state (SBS) mode and an accidental (AC) SBS mode within the bandgap. With a period size of 5 × 15, the bandgap effectively filters out the continuum, allowing only the bound states to exist. This configuration enabled us to achieve a high signal-to-noise ratio and a wide free-spectral-range. The AC SBS and the SP SBS can be converted into quasi-SBS by adjusting different parameters. Consequently, the cavity can function as a single-band sensor or a dual-band sensor. The achieved bulk sensitivity was 38 µm/RIU in terahertz wave band, and a record-high FOM reached 2.8 × 108 RIU-1. The effect of fabrication error on the performance for sensor application was also discussed, showing that the application was feasible. Moreover, for experimental realization, a 3D schematic was presented. These achievements pave the way for compact, high-sensitivity biosensing, multi-wavelength sensing, and other promising applications.

Exploring the therapeutic potential of a nano micelle containing a carbon monoxide-releasing molecule for metabolic-associated fatty liver disease by modulating hypoxia-inducible factor-1α.

Metabolic-associated fatty liver disease (MAFLD) encompasses a spectrum of chronic liver diseases, including steatohepatitis, cirrhosis, and liver cancer. Despite the increasing prevalence and severity of MAFLD, no approved pharmacological interventions are currently available. Hypoxia-inducible factor-1α (HIF-1α) has emerged as a crucial early mediator in the pathogenesis of MAFLD. Previously, we demonstrated the potent anti-inflammatory properties of the nano-designed carbon monoxide (CO) donor, styrene maleic acid copolymer (SMA) encapsulating CO-releasing molecule (SMA/CORM2), which effectively suppressed HIF-1α in various inflammatory disorders. Here, we investigated the therapeutic potential of SMA/CORM2 in a mouse model of MAFLD induced by a high-fat methionine- and choline-deficient (HF-MCD) diet. Following 4 weeks of HF-MCD diet consumption, we observed pronounced hepatic lipid accumulation accompanied by disrupted lipid metabolism, polarization of macrophages towards the pro-inflammatory M1 phenotype, activation of the NLRP3 inflammasome, and upregulation of the TGF-ß fibrosis signaling pathway. Notably, the early and upstream event driving these pathological changes was the upregulation of HIF-1α. Treatment with SMA/CORM2 (10 mg/kg, three times per week) led to a significant increase in CO levels in both the circulation and liver, resulting in remarkable suppression of HIF-1α expression even before the onset of apparent pathological changes induced by the HF-MCD diet. Consequently, SMA/CORM2 administration exerted a significantly protective and therapeutic effect on MAFLD. In vitro studies using hepatocytes treated with high concentrations of fatty acids further supported these findings, as knockdown of HIF-1α using short hairpin RNA (shRNA) elicited similar effects to SMA/CORM2 treatment. Collectively, our results highlight the therapeutic potential of SMA/CORM2 in the management of MAFLD through suppression of HIF-1α. We anticipate that SMA/CORM2, with its ability to modulate HIF-1α expression, may hold promise for future applications in the treatment of MAFLD. STATEMENT OF SIGNIFICANCE: Carbon monoxide (CO) is a crucial gaseous signaling molecule that plays a vital role in maintaining homeostasis and is a potential target for treating many inflammatory diseases. Developing drug delivery systems that can deliver CO stably and target specific tissues is of great interest. Our team previously developed a nano micellar CO donor, SMA/CORM2, which exhibits superior bioavailability to native CORM2 and shows therapeutic potential in many inflammatory disease models. In this study, we showed that SMA/CORM2, through controlled CO release, significantly ameliorated steatohepatitis and liver fibrosis induced by an HF-MCD diet by suppressing an HIF-1α mediated inflammatory cascade. These findings provide new insight into the anti-inflammatory function of CO and a promising approach for controlling metabolic-associated fatty liver disease.

Superbound state in photonic bandgap and its application to generate complete tunable SBS-EIT, SBS-EIR and SBS-Fano.

Bound states in continua (BICs) have high-quality factors that may approach infinity. However, the wide-band continua in BICs are noise to the bound states, limiting their applications. Therefore, this study designed fully controlled superbound state (SBS) modes in the bandgap with ultra-high-quality factors approaching infinity. The operating mechanism of the SBS is based on the interference of the fields of two phase-opposite dipole sources. Quasi-SBSs can be obtained by breaking the cavity symmetry. The SBSs can also be used to produce high-Q Fano resonance and electromagnetically-induced-reflection-like modes. The line shapes and the quality factor values of these modes could be controlled separately. Our findings provide useful guidelines for the design and manufacture of compact and high-performance sensors, nonlinear effects, and optical switches.

Valorization of Biomass-Derived Polymers to Functional Biochar Materials for Supercapacitor Applications via Pyrolysis: Advances and Perspectives.

Polymers from biomass waste including plant/forest waste, biological industrial process waste, municipal solid waste, algae, and livestock are potential sources for renewable and sustainable resources. Converting biomass-derived polymers to functional biochar materials via pyrolysis is a mature and promising approach as these products can be widely utilized in many areas such as carbon sequestration, power production, environmental remediation, and energy storage. With abundant sources, low cost, and special features, the biochar derived from biological polymeric substances exhibits great potential to be an alternative electrode material of high-performance supercapacitors. To extend this scope of application, synthesis of high-quality biochar will be a key issue. This work systematically reviews the char formation mechanisms and technologies from polymeric substances in biomass waste and introduces energy storage mechanisms of supercapacitors to provide overall insight into the biological polymer-based char material for electrochemical energy storage. Aiming to enhance the capacitance of biochar-derived supercapacitor, recent progress in biochar modification approaches including surface activation, doping, and recombination is also summarized. This review can provide guidance for valorizing biomass waste to functional biochar materials for supercapacitor to meet future needs.

Frequency-domain-resolved investigation of unitary h-shaped pulses.

We experimentally investigate the generation of h-shaped pulse in an all-polarization-maintaining (PM) and all-normal-dispersion (ANDi) mode-locked fiber laser. The generated pulse is demonstrated to be a unitary pulse, instead of a noise-like pulse (NLP). Furthermore, by employing an external filtering system, the obtained h-shaped pulse can be resolved into rectangular-shaped pulses, chair-like pulses, and Gaussian pulses. The authentic AC traces with a double-scale structure of unitary h-shaped pulses and chair-like pulses are observed on the autocorrelator. The chirp of h-shaped pulses is also proved similar to that of DSR pulses. To the best of our knowledge, this is the first time that the existence of unitary h-shaped pulse generation has been confirmed. Moreover, our experimental results reveal the close relationship of formation mechanisms of dissipative soliton resonance (DSR) pulses, h-shaped pulses, and chair-like pulses, which helps to unify the essences of such "DSR-like" pulses.

976†nm all-polarization-maintaining mode-locked fiber laser based on nonlinear polarization evolution.

An all-polarization-maintaining (PM) mode-locked fiber laser based upon nonlinear polarization evolution (NPE) that operates around 976 nm is presented. The NPE-based mode-locking is realized using a special section of the laser which comprises three pieces of PM fibers with specific deviation angles between the polarization axes and a polarization-dependent isolator. By optimizing the NPE section and adjusting the pump power, dissipative soliton (DS) pulses with a pulse duration of ∼6 ps, a spectral bandwidth of >10 nm and a maximum pulse energy of 0.54 nJ are generated. Self-starting, steady mode-locking operation is achievable within a pump power range of ∼2 W. Moreover, by incorporating a segment of passive fiber into the appropriate location in the laser resonator, an intermediate regime between stable single-pulse mode-locking and noise-like pulse (NLP) is realized in the laser. Our work expands the dimension of the research on the mode-locked Yb-doped fiber laser operating around 976 nm.