Exosomes derived from induced cardiopulmonary progenitor cells alleviate acute lung injury in mice.

Cardiopulmonary progenitor cells (CPPs) constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth. This fact offers the possibility for the treatment of pulmonary heart disease (PHD), in which the lung and heart are both damaged. A reliable source of CPPs is urgently needed. In this study, we reprogrammed human cardiac fibroblasts (HCFs) into CPP-like cells (or induced CPPs, iCPPs) and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury (ALI). iCPPs were created in passage 3 primary HCFs by overexpressing GLI1, WNT2, ISL1 and TBX5 (GWIT). Exosomes were isolated from the culture medium of passage 6-8 GWIT-iCPPs. A mouse ALI model was established by intratracheal instillation of LPS. Four hours after LPS instillation, ALI mice were treated with GWIT-iCPP-derived exosomes (5 × 109, 5 × 1010 particles/mL) via intratracheal instillation. We showed that GWIT-iCPPs could differentiate into cell lineages, such as cardiomyocyte-like cells, endothelial cells, smooth muscle cells and alveolar epithelial cells, in vitro. Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development. Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation, promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier. This study provides a potential new method for the prevention and treatment of cardiopulmonary injury, especially lung injury, and provides a new cell model for drug screening.

Comparative genomics of macaques and integrated insights into genetic variation and population history.

The crab-eating macaques ( Macaca fascicularis ) and rhesus macaques ( M. mulatta ) are widely studied nonhuman primates in biomedical and evolutionary research. Despite their significance, the current understanding of the complex genomic structure in macaques and the differences between species requires substantial improvement. Here, we present a complete genome assembly of a crab-eating macaque and 20 haplotype-resolved macaque assemblies to investigate the complex regions and major genomic differences between species. Segmental duplication in macaques is ∼42% lower, while centromeres are ∼3.7 times longer than those in humans. The characterization of ∼2 Mbp fixed genetic variants and ∼240 Mbp complex loci highlights potential associations with metabolic differences between the two macaque species (e.g., CYP2C76 and EHBP1L1 ). Additionally, hundreds of alternative splicing differences show post-transcriptional regulation divergence between these two species (e.g., PNPO ). We also characterize 91 large-scale genomic differences between macaques and humans at a single-base-pair resolution and highlight their impact on gene regulation in primate evolution (e.g., FOLH1 and PIEZO2 ). Finally, population genetics recapitulates macaque speciation and selective sweeps, highlighting potential genetic basis of reproduction and tail phenotype differences (e.g., STAB1 , SEMA3F , and HOXD13 ). In summary, the integrated analysis of genetic variation and population genetics in macaques greatly enhances our comprehension of lineage-specific phenotypes, adaptation, and primate evolution, thereby improving their biomedical applications in human diseases.

Gli1-mediated tumor cell-derived bFGF promotes tumor angiogenesis and pericyte coverage in non-small cell lung cancer.

BACKGROUND: Tumor angiogenesis inhibitors have been applied for non-small cell lung cancer (NSCLC) therapy. However, the drug resistance hinders their further development. Intercellular crosstalk between lung cancer cells and vascular cells was crucial for anti-angiogenenic resistance (AAD). However, the understanding of this crosstalk is still rudimentary. Our previous study showed that Glioma-associated oncogene 1 (Gli1) is a driver of NSCLC metastasis, but its role in lung cancer cell-vascular cell crosstalk remains unclear. METHODS: Conditioned medium (CM) from Gli1-overexpressing or Gli1-knockdown NSCLC cells was used to educate endothelia cells and pericytes, and the effects of these media on angiogenesis and the maturation of new blood vessels were evaluated via wound healing assays, Transwell migration and invasion assays, tube formation assays and 3D coculture assays. The xenograft model was conducted to establish the effect of Gli1 on tumor angiogenesis and growth. Angiogenic antibody microarray analysis, ELISA, luciferase reporte, chromatin immunoprecipitation (ChIP), bFGF protein stability and ubiquitination assay were performed to explore how Gli1 regulate bFGF expression. RESULTS: Gli1 overexpression in NSCLC cells enhanced the endothelial cell and pericyte motility required for angiogenesis required for angiogenesis. However, Gli1 knockout in NSCLC cells had opposite effect on this process. bFGF was critical for the enhancement effect on tumor angiogenesis. bFGF treatment reversed the Gli1 knockdown-mediated inhibition of angiogenesis. Mechanistically, Gli1 increased the bFGF protein level by promoting bFGF transcriptional activity and protein stability. Importantly, suppressing Gli1 with GANT-61 obviously inhibited angiogenesis. CONCLUSION: The Gli1-bFGF axis is crucial for the crosstalk between lung cancer cells and vascular cells. Targeting Gli1 is a potential therapeutic approach for NSCLC angiogenesis.

Association of cardiometabolic and triglyceride-glucose index with left ventricular diastolic function in asymptomatic individuals.

BACKGROUND AND AIMS: Obesity and insulin resistance are associated with left ventricular diastolic dysfunction (LVDD) and increased risk of heart failure. Cardiometabolic index (CMI) and triglyceride glucose (TyG) are new indexes to assess visceral obesity and insulin resistance, respectively. The study aimed to investigate the clinical usefulness of these indexes for identifying LVDD individuals. METHODS AND RESULTS: Overall, 1898 asymptomatic individuals were included in this cross-sectional study. Participants underwent anthropometrics, serum biochemical evaluation, and echocardiography. Multiple linear regression analysis revealed that both indexes were independent determinants of diastolic parameters among females; while for males, CMI and TyG were not associated with A velocity. In the multivariate logistic analysis, the proportion of LVDD in the third and fourth quartiles of CMI remained significantly greater than that in the lowest quartile in females (Q3 vs. Q1: odds ratio (OR) = 2.032, 95% confidence interval (CI): 1.181-3.496; Q4 vs. Q1: OR = 2.393, 95% CI: 1.347-4.249); while in males, the incidence of LVDD was significantly greater only in the fourth quartile. For TyG, the presence of LVDD in the fourth quartile was significantly greater in both genders. The discriminant values between the CMI (AUC: 0.704, 95% CI: 0.668-0.739) and TyG (AUC: 0.717, 95% CI: 0.682-0.752) were similar in females. Both indexes performed better in females than in males to identify LVDD. CONCLUSION: The CMI and TyG might both serve as effective tools to identify LVDD in routine health check-ups in primary care, mainly in females. With simpler parameters, the CMI could be utilized in medically resource-limited areas.

Structurally divergent and recurrently mutated regions of primate genomes.

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or ∼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.

Comparative transcriptome analysis between rhesus macaques ( Macaca mulatta) and crab-eating macaques ( M. fascicularis).

Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques ( Macaca mulatta, MMU) and crab-eating macaques ( M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from 84 samples (41 MFA samples and 43 MMU samples) encompassing 14 common tissues. Our findings revealed a small fraction of genes (3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover, 19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary, this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.

Plastic particles affect N2O release via altering core microbial metabolisms in constructed wetlands.

Constructed wetlands (CWs) have been proven to effectively immobilize plastic particles. However, little is known about the differences in the impact of varying sized plastic particles on nitrous oxide (N2O) release, as well as the intervention mechanisms in CWs. Here, we built a lab-scale wetland model and introduced plastic particles of macro-, micro-, and nano-size at 100 µg/L for 370 days. The results showed that plastic particles of all sizes reduced N2O release in CWs, with the degrees being the strongest for the Nano group, followed by Micro and Macro groups. Meanwhile, 15N- and 18O-tracing experiment revealed that the ammoxidation process contributed the most N2O production, followed by denitrification. While for every N2O-releasing process, the contributing proportion of N2O in nitrification-coupled denitrification were most significantly cut down under exposing to macro-sized plastics and had an obvious increase in nitrifier denitrification in all groups, respectively. Finally, we revealed the three mechanism pathways of N2O release reduction with macro-, micro-, and nano-sized plastics by impacting carbon assimilation (RubisCO activity), ammonia oxidation (gene amo abundance and HAO activity), and N-ion transmembrane and reductase activities, respectively. Our findings thus provided novel insights into the potential effects of plastic particles in CWs as an eco-technology.

Interfacial Polarization Control Engineering and Ferroelectric PZT/Graphene Heterostructure Integrated Application.

Integration and miniaturization are the inevitable trends in the development of electronic devices. PZT and graphene are typical ferroelectric and carbon-based materials, respectively, which have been widely used in various fields. Achieving high-quality PZT/graphene heterogeneous integration and systematically studying its electrical properties is of great significance. In this work, we reported the characterization of a PZT film based on the sol-gel method. Additionally, the thickness of the PZT film was pushed to the limit size (~100 nm) by optimizing the process. The test results, including the remnant and leakage current, show that the PZT film is a reliable and suitable platform for further graphene-integrated applications. The non-destructive regulation of the electrical properties of graphene has been studied based on a domain-polarized substrate and strain-polarized substrate. The domain structures in the PZT film exhibit different geometric structures with ~0.3 V surface potential. The I-V output curves of graphene integrated on the surface of the PZT film exhibited obvious rectification characteristics because of p/n-doping tuned by an interfacial polarized electric field. In contrast, a ~100 nm thick PZT film makes it easy to acquire a larger strain gradient for flexural potential. The tested results also show a rectification phenomenon, which is similar to domain polarization substrate regulation. Considering the difficulty of measuring the flexural potential, the work might provide a new approach to assessing the flexural polarized regulation effect. A thinner ferroelectric film/graphene heterojunction and the polarized regulation of graphene will provide a platform for promoting low-dimension film-integrated applications.

A Phase 2 Trial of Primary Tumor Stereotactic Body Radiation Therapy Boost Before Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer.

PURPOSE: Primary tumor failure is common in patients treated with chemoradiation (CRT) for locally advanced NSCLC (LA-NSCLC). Stereotactic body radiation therapy (SBRT) yields high rates of primary tumor control (PTC) in early-stage NSCLC. This trial tested an SBRT boost to the primary tumor before the start of CRT to improve PTC. METHODS AND MATERIALS: Patients with LA-NSCLC received an SBRT boost in 2 fractions (central location 12 Gy, peripheral location 16 Gy) to the primary tumor, followed by standard CRT (60 Gy in 30 fractions). The primary objective was PTC rate at 1 year, and the hypothesis was that the 1-year PTC rate would be ≥90%. Secondary objectives included objective response rate, regional and distant control, disease-free survival (DFS), and overall survival (OS). Correlative studies included functional magnetic resonance imaging and blood-based miRNA analysis. RESULTS: The study enrolled 21 patients (10 men and 11 women); the median age was 62 years (range, 52-78). The median pretreatment primary tumor size was 5.0 cm (range, 1.0-8.3). The most common nonhematologic toxicities were pneumonitis, fatigue, esophagitis/dysphagia, dyspnea, and cough. Only 1 treatment-related grade 4 nonhematologic toxicity occurred (respiratory failure/radiation pneumonitis), and no grade 5 toxicities occurred. The objective response rate at 3 and 6 months was 72.7% and 80.0%, respectively, and PTC at 1 and 2 years was 100% and 92.3%, respectively. The 2-year regional and distant control rates were 81.6% and 70.3%, respectively. Disease-free survival and overall survival at 2 years were 46.1% and 50.3%, respectively, and median survival was 37.8 months. Functional magnetic resonance imaging detected a mean relative decrease in blood oxygenation level-dependent signal of -87.1% (P = .05), and miR.142.3p was correlated with increased risk of grade ≥3 pulmonary toxicity (P = .01). CONCLUSIONS: Dose escalation to the primary tumor using upfront SBRT appears feasible and safe. PTC was high and other oncologic endpoints compared favorably to standard treatment. Functional magnetic resonance imaging suggested changes in oxygenation with the first SBRT boost dose, and miR.142.3p was correlated with pulmonary toxicity.

The outcomes of COVID-19 and acute pancreatitis: a systematic review and meta-analysis.

Background: Coronavirus disease 2019 (COVID-19) was first reported in China at the end of 2019. Several case studies have documented a probable association between infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and acute pancreatitis (AP). The objective of this study was to provide a complete analysis of existing literature that compares the clinical outcomes of AP in patients with COVID-19 and those without COVID-19. The intention was to further our understanding of the involvement of SARS-CoV-2 in the development of pancreatitis. Methods: Between January 2019 and December 2022, we searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus. Nine studies (3,160 patients) were included. In this meta-analysis, Stata 12.0. was utilized. The information provided in this study is presented following the MOOSE reporting checklist. Results: Mortality [odds ratio (OR) =3.95, 95% confidence interval (CI): 2.87, 5.43, P<0.001], intensive care unit (ICU) administration (OR =3.74, 95% CI: 2.26, 6.20, P<0.001), mechanical ventilation (OR =4.84, 95% CI: 2.14, 10.96, P<0.001), severe pancreatitis (OR =2.71, 95% CI: 1.04, 7.04, P=0.042), etiology of idiopathic and unknown (OR =4.75, 95% CI: 1.80, 12.56, P=0.002), necrotizing pancreatitis (OR =1.88, 95% CI: 1.28, 2.76, P=0.001), and length of hospital stay [weighted mean difference (WMD) =5.10, 95% CI: 2.79, 7.41, P<0.001] were more significantly increased in AP cases with COVID-19 than those without it. Conclusions: In conclusion, the findings of this study indicate a potential worsening of AP outcomes in patients affected by COVID-19.

Proximal aorta dilatation in hypertension.

Dilation of the proximal aorta is a common clinical manifestation in hypertensive patients. Although it is straightforward to link hypertension with proximal aortic dilation, previous studies on their interrelation have yielded controversial results. Cross-sectional design, methodology of blood pressure assessment, confounding factors like medications, and inconsistent reference values may lead to the paradoxical conclusions. Recently, advances have been made in the exploration of determinants and clinical value of proximal aortic dilatation. Thus, we reviewed these findings and summarized that aortic dilatation may be the consequence of hemodynamic and nonhemodynamic co-factors' combined action. Moreover, proximal aortic dilatation tends to be a predictor for aortic aneurysm dissection or rupture, hypertensive target organ damage as well as cardiovascular events. The present review contributes to a comprehensive understanding of the pathological process of proximal aortic dilatation in hypertension.

Population genetics of marmosets in Asian primate research centers and loci associated with epileptic risk revealed by whole-genome sequencing.

The common marmoset ( Callithrix jacchus) has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies. Epileptic marmosets have been independently reported in two Asian primate research centers. Nevertheless, the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated. Here, we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing. We identified 14 558 184 single nucleotide polymorphisms (SNPs) from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples. Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers. In addition, SNP and copy number variation (CNV) analyses suggested that the WW domain-containing oxidoreductase ( WWOX) and Tyrosine-protein phosphatase nonreceptor type 21 ( PTPN21) genes may be associated with epilepsy in marmosets. Notably, KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets. This study provides valuable population genomic resources for marmosets in two Asian primate centers. Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers, while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.

Characterization of large-scale genomic differences in the first complete human genome.

BACKGROUND: The first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release is a milestone in human genomics. The T2T-CHM13 genome assembly extends our understanding of telomeres, centromeres, segmental duplication, and other complex regions. The current human genome reference (GRCh38) has been widely used in various human genomic studies. However, the large-scale genomic differences between these two important genome assemblies are not characterized in detail yet. RESULTS: Here, in addition to the previously reported "non-syntenic" regions, we find 67 additional large-scale discrepant regions and precisely categorize them into four structural types with a newly developed website tool called SynPlotter. The discrepant regions (~ 21.6 Mbp) excluding telomeric and centromeric regions are highly structurally polymorphic in humans, where the deletions or duplications are likely associated with various human diseases, such as immune and neurodevelopmental disorders. The analyses of a newly identified discrepant region-the KLRC gene cluster-show that the depletion of KLRC2 by a single-deletion event is associated with natural killer cell differentiation in ~ 20% of humans. Meanwhile, the rapid amino acid replacements observed within KLRC3 are probably a result of natural selection in primate evolution. CONCLUSION: Our study provides a foundation for understanding the large-scale structural genomic differences between the two crucial human reference genomes, and is thereby important for future human genomics studies.

Is there a bidirectional relationship between workplace bullying and the risk of sickness absence? Systematic review and meta-analysis of prospective studies.

Exposure to workplace bullying increases the risk of sickness absence. However, the extent and direction of this relationship for different follow-up lengths are not well established. To provide evidence regarding the direction and extent of the relationship between workplace bullying and different durations of sickness absence. We searched nine databases from their inception to 29 November 2022. Multiple independent observers screened the literature, extracted the data and used the Risk Of Bias In Non-randomised Studies of Exposure to assess the methodological quality. The overall effect sizes of odds ratio, relative risk, hazard ratio and 95% confidence intervals were calculated. Our meta-analysis demonstrated a 26% increased risk of sick leave among workers exposed to workplace bullying for all follow-up lengths (95% CI 1.18 to 1.35), even after adjusting for confounding factors. Moreover, we found a significant association between long-term sickness absence and a higher likelihood of subsequent exposure to workplace bullying, with a pooled OR of 1.63 (95% CI 1.21 to 2.04). Our study established a bidirectional relationship between workplace bullying and long-term sickness absence, highlighting that it increases the risk of sickness absence at different follow-up lengths among employees who have been bullied. Hence, organisations should be mindful of workers who resume work after prolonged absences due to illness and adopt appropriate management strategies to prevent workplace bullying.

Biochar boosts nitrate removal in constructed wetlands for secondary effluent treatment: Linking nitrate removal to the metabolic pathway of denitrification and biochar properties.

Constructed wetlands (CWs) amended with biochar have attracted much attention for nitrate removal treating secondary effluent. However, little is acknowledged about the linkage among the nitrate removal performance, microbial metabolic pathway of nitrate, and biochar properties. Herein, biochars pyrolyzed under 300 °C, 500 °C, and 700 °C (BC300, BC500, and BC700, respectively) were used in CWs to reveal the relationship. Results showed that CWs amended with BC300 (59.73%), BC500 (53.27%), and BC700 (49.07%) achieved higher nitrogen removal efficiency, compared with the control (39.51%). Metagenomic analysis showed that biochars could enrich the genes, which encoded key enzymes (adenosine triphosphate production, and electrons generation, transportation, and consumption) involved in carbon and nitrate metabolism. Further, biochar pyrolyzed under lower temperature, with higher oxygen content, molar O/C ratio, and the electron donating capacity, in CWs could obtain higher nitrate removal efficiency. Overall, this research offers new understandings for the promotion of denitrification in CWs amended with biochar.

Primary headache disorders: From pathophysiology to neurostimulation therapies.

Primary headache disorders including migraine, cluster headache, and tension-type headache are among the most common disabling diseases worldwide. The unclear pathogenesis of primary headache disorders has led to high rates of misdiagnosis and limited available treatment options. In this review, we have summarized the pathophysiological factors for a better understanding of primary headache disorders. Advances in functional neuroimaging, genetics, neurophysiology have indicated that cortical hyperexcitability, regional brain dysfunction, central sensitization and neuroplasticity changes play vital roles in the development of primary headache disorders. Moreover, we have also discussed a series of neurostimulation approaches with their stimulation mechanism, safety and efficacy for prevention and treatment of primary headache disorders. Noninvasive or implantable neurostimulation techniques show great promise for treating refractory primary headache disorders.

Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.

Hypertension is a global public health issue and the leading cause of premature death in humans. Despite more than a century of research, hypertension remains difficult to cure due to its complex mechanisms involving multiple interactive factors and our limited understanding of it. Hypertension is a condition that is named after its clinical features. Vascular function is a factor that affects blood pressure directly, and it is a main strategy for clinically controlling BP to regulate constriction/relaxation function of blood vessels. Vascular elasticity, caliber, and reactivity are all characteristic indicators reflecting vascular function. Blood vessels are composed of three distinct layers, out of which the endothelial cells in intima and the smooth muscle cells in media are the main performers of vascular function. The alterations in signaling pathways in these cells are the key molecular mechanisms underlying vascular dysfunction and hypertension development. In this manuscript, we will comprehensively review the signaling pathways involved in vascular function regulation and hypertension progression, including calcium pathway, NO-NOsGC-cGMP pathway, various vascular remodeling pathways and some important upstream pathways such as renin-angiotensin-aldosterone system, oxidative stress-related signaling pathway, immunity/inflammation pathway, etc. Meanwhile, we will also summarize the treatment methods of hypertension that targets vascular function regulation and discuss the possibility of these signaling pathways being applied to clinical work.

Structurally divergent and recurrently mutated regions of primate genomes.

To better understand the pattern of primate genome structural variation, we sequenced and assembled using multiple long-read sequencing technologies the genomes of eight nonhuman primate species, including New World monkeys (owl monkey and marmoset), Old World monkey (macaque), Asian apes (orangutan and gibbon), and African ape lineages (gorilla, bonobo, and chimpanzee). Compared to the human genome, we identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. Across 50 million years of primate evolution, we estimate that 819.47 Mbp or ~27% of the genome has been affected by SVs based on analysis of these primate lineages. We identify 1,607 structurally divergent regions (SDRs) wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (CARDs, ABCD7, OLAH) and new lineage-specific genes are generated (e.g., CKAP2, NEK5) and have become targets of rapid chromosomal diversification and positive selection (e.g., RGPDs). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species for the first time.

Janus biomass aerogel for Highly-Efficient steam Generation, Desalination, degradation of organics and water disinfection.

Solar-driven water purification has been deemed as a cheap, green and renewable technology to mitigate water shortage and pollution. Herein, a biomass aerogel with hydrophilic-hydrophobic Janus structure has been prepared as solar water evaporator, which is achieved by partially modifying hydrothermal-treated loofah sponge (HLS) with reduced graphene oxide (rGO). It's a rare design philosophy that HLS serves as a substrate with large pores and hydrophilic properties to ensure continuous and effective water transport, and the hydrophobic layer with rGO modification guarantees good salt resistance in seawater desalination with high photothermal conversion efficiency. As a result, the obtained Janus aerogel, p-HLS@rGO-12, exhibits impressive solar-driven evaporation rates of 1.75 kg m-2h-1 and 1.54 kg m-2h-1 for pure water and seawater respectively, with good cycling stability in the evaporation process. Furthermore, p-HLS@rGO-12 also demonstrates outstanding photothermal degradation of rhodamine B (greater than98.8 % in 2 h) and sterilization of E. coli (nearly 100 % in 2 h). This work offers an unusual approach to achieve highly efficient solar-driven steam generation, seawater desalination, organic pollutant degradation, and water disinfection simultaneously. The prepared Janus biomass aerogel holds great potential application in the field of seawater desalination and wastewater purification.

A multi-center retrospective study on the efficacy and safety of regorafenib vs. regorafenib combined with PD-1 inhibitors as a second-line therapy in patients with advanced hepatocellular carcinoma.

Background: At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the combination therapy of regorafenib and programmed death-1 (PD-1) inhibitors with regorafenib monotherapy as a second-line treatment for patients with advanced HCC. Methods: Our multicenter retrospective study evaluated consecutive patients with advanced HCC who received regorafenib plus PD-1 inhibitors or regorafenib alone as a later-line therapy from May 2019 to January 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, and safety was assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: A total of 133 patients were included in the study (regardless of first-line treatment), including 94 who received regorafenib plus PD-1 inhibitors and 39 who received regorafenib. The regorafenib plus PD-1 inhibitors group had a significantly higher ORR (25.53% vs. 10.26%, P=0.015), higher DCR (87.23% vs. 66.67%, P=0.006), and longer PFS (median 9.0 vs. 4.0 months, P<0.0001) than the regorafenib group. Meanwhile, the median OS (mOS) did not differ between the regorafenib plus PD-1 and regorafenib monotherapy groups {mOS, 14.0 months [95% confidence interval (CI), 14.0-16.0 months] vs. 12.0 months (95% CI, 10.0-22.0 months)}. There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (71.79% vs. 78.72%, P=0.39) and the incidence of grade 3/4 serious adverse effects (5.13% vs. 18.09%, P=0.19) between the regorafenib monotherapy group and PD-1 inhibitors combination group. Conclusions: Compared with regorafenib alone, regorafenib combined with PD-1 inhibitors therapy increased PFS, ORR but did not improve OS, and can be used an option in second-line HCC therapy, regardless of first-line treatments. Regorafenib combined with PD-1 inhibitors is recommended as early as a second-line therapy to benefit patients. The combination regimen was as safe as regorafenib monotherapy for treatment of HCC in patients with compensated liver disease [Child-Turcotte-Pugh (CTP) A/B].