Resveratrol liposomes reverse sorafenib resistance in renal cell carcinoma models by modulating PI3K-AKT-mTOR and VHL-HIF signaling pathways.

RCC is a malignant tumor arising from the urothelium of renal parenchyma that remains challenging to be treated. In this study, we assessed the anti-tumor effects of Resveratrol liposomes (RES-lips) combined with sorafenib on renal cell carcinoma (RCC) and explored the potential mechanisms underlying the improvement of sorafenib resistance models. Tumor growth and survival following treatment with sorafenib alone or in combination with RES-lips was evaluated in a RCC xenograft mouse model. Flow cytometry results demonstrated that the combination of RES-lips and sorafenib significantly enhanced the G1/S phase arrest of sorafenib-resistant cells. When compared with the PBS or monotherapy groups, treatment with RES-lips combined with sorafenib exhibited significant inhibition of tumor growth in the RCC xenograft mouse model with tumor growth inhibition (TGI) rates and complete remission (CR) rates of 90.1 % and 50 %, respectively. Concersely, the maximum TGI rate was 53.6 % in the RES-lips monoherapy group and 29.2 % and in the sorafenib monotherapy group, and no animals achieved CR. Additionally, the current combination therapy promoted the proliferation of unactivated splenic lymphocytes and the proliferation of soybean protein A- and lipopolysaccharide-stimulated lymphocytes compared with PBS or monotherapy treatments. Further western blotting analysis suggested that RES-lips may enhance the resistance of RCC to sorafenib by inhibiting PI3K-AKT-mTOR and VHL-HIF signaling pathways, ultimately augmenting the tumor growth inhibition effect of the combination therapy. RES-lips may improve the sorafenib resistance in RCC, and the underlying mechanism may be related to the regulation of PI3K-AKT-mTOR and VHL-HIF signaling pathways.

Elevating water table reduces net ecosystem carbon losses from global drained wetlands.

Drained wetlands are thought to be carbon (C) source hotspots, and rewetting is advocated to restore C storage in drained wetlands for climate change mitigation. However, current assessments of wetland C balance mainly focus on vertical fluxes between the land and atmosphere, frequently neglecting lateral carbon fluxes and land-use effects. Here, we conduct a global synthesis of 893 annual net ecosystem C balance (NECB) measures that include net ecosystem exchange of CO2, along with C input via manure fertilization, and C removal through biomass harvest or hydrological exports of dissolved organic and inorganic carbon, across wetlands of different status and land uses. We find that elevating water table substantially reduces net ecosystem C losses, with the annual NECB decreasing from 2579 (95% interval: 1976 to 3214) kg C ha-1 year-1 in drained wetlands to -422 (-658 to -176) kg C ha-1 year-1 in natural wetlands, and to -934 (-1532 to -399) kg C ha-1 year-1 in rewetted wetlands globally. Climate, land-use history, and time since water table changes introduce variabilities, with drainage for (sub)tropical agriculture or forestry uses showing high annual C losses, while the net C losses from drained wetlands can continue to affect soil C pools for several decades. Rewetting all types of drained wetlands is needed, particularly for those formerly agriculture-used (sub)tropical wetlands where net ecosystem C losses can be largely reduced. Our findings suggest that elevating water table is an important initiative to reduce C losses in degraded wetlands, which could contribute to policy decisions for managing wetlands to enhance their C sequestration.

A novel strategy for recovery of heavy metals and synthesis of Co-rich alloy from the alkali-treated tungsten residue using photovoltaic silicon kerf waste.

The treatment of spent cemented carbides using the conventional alkali-acid leaching process results in the generation of hazardous solid waste tungsten leaching residue. This study proposed an alternative process using the alkali-treated tungsten leaching residue (AW-residue) without the acid leaching step, preserving Co in the residue. By using photovoltaic silicon kerf waste (SKW) as a reducing agent, heavy metals (Co, Ni, W, Nb, and Ta) were efficiently extracted from AW-residue and a Co-rich alloy was obtained. The silicothermic reduction process facilitated the recovery of iron group metals (Co, Ni, and Fe) and effectively captured trace refractory metals (W, Ta, and Nb). Phase separation occurred through reduction reaction and viscosity-driven processes between the Co-rich alloy and the slag. Optimal conditions were identified as 20% SKW addition, MgO crucible, and a holding time of 120 min, achieving a total recovery yield of 95.5%, with specific yields for Co (97.7%), Ni (97.0%), W (82.5%), Nb (76.3%), and Ta (70.5%). A 20 kg pilot-scale experiment confirmed the feasibility of the process, yielding 47.0% Co-rich alloy from AW-residue compared to 48.3% in lab-scale experiment, and producing a harmless slag phase. This environmentally friendly approach promotes sustainable recycling of valuable metals in the tungsten industry.

Association between dietary fiber intake and kidney stones: results from the National Health and Nutrition Examination Survey (2011-2018).

BACKGROUND/OBJECTIVES: Studies on the impact of dietary fiber intake on kidney stones are few, and their results were controversial. This study aimed to explore the association between dietary fiber intake and kidney stones in the nationally representative population of the USA. SUBJECTS/METHODS: This cross-sectional research included 8,588 participants from the National Health and Nutrition Examination Survey, 2011 to 2018. Information regarding dietary fiber intake was obtained from a 24-h recall survey. Participants were categorized into different dietary fiber intake tertiles according to the average of 2 days of dietary recall data. The outcome was self-reported kidney stones. After adjusting for the traditional risk factors, a multivariate logistic regression model was used to examine the association between dietary fiber intake and kidney stones. RESULTS: Eight hundred seventy-two participants had kidney stones. The weighted prevalence (SE) of kidney stones in the lowest tertile, medium tertile, and highest tertile of dietary fiber intake was 11.8% (0.8%), 10.3% (0.8%), and 9.1% (0.8%), respectively. After adjusting for age, sex, race and ethnicity, education level, smoking status, alcohol consumption, physical activity, body mass index, hypertension, diabetes, dyslipidemia, daily water intake, chronic kidney disease stage 3-5, and total energy intake, participants with the highest tertile of fiber intake had a significantly lower risk of kidney stones (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.48-0.95) compared to those in the lowest tertile. Every 5 g/day increment in dietary fiber intake was associated with a significant decrease in risk of kidney stones (OR, 0.90; 95% CI, 0.83-0.98). CONCLUSION: An increase in dietary fiber intake was associated with a lower risk of kidney stones, suggesting adults should be encouraged to maintain an adequate dietary fiber intake to prevent the development of kidney stones. Our results provide evidence to formulate nutrition management strategies for the prevention of kidney stones.

Thiopyran-Fused Polycyclic Aromatic Compounds Synthesized via Pt(II)-Catalyzed One-Pot Ring-Expansion and 6-endo Cyclization Reactions.

A series of thiopyran-fused polycyclic aromatic hydrocarbons (PAHs) have been straightforwardly synthesized from 2,5-di(1-en-3-ynyl)thiophene-containing precursors via one-pot ring-expansion and 6-endo cyclization reactions. The reaction monitoring and the density function theoretical calculation suggest that the ring-expansion reaction occurs prior to 6-endo cyclization. Moreover, the absorption profiles of the thiopyran-fused PAHs suggest that the π-conjugation extension on the side of the cyclopentadiene ring in the cyclopenta[b]thiochromene core is predominant in prolonging the effective conjugation length, while the effect from extension on the other side is negligible. Furthermore, all of the thiopyran-fused PAHs exhibit halochromic properties. Upon the addition of trifluoromethanesulfonic acid, fluorescence "off-on" switches can be found for these thiopyran-fused PAHs. Therefore, this work not only provides a new synthetic approach for one-pot ring-expansion and 6-endo cyclization reactions but also expands the diversity of thiopyran-fused PAHs.

Synergistic utilization of industrial solid wastes: Extraction of valuable metals from tungsten leaching residue by photovoltaic sawing waste.

Solid waste challenges in both the tungsten and photovoltaic industries present significant barriers to achieving carbon neutrality. This study introduces an innovative strategy for the efficient extraction of valuable metals from hazardous tungsten leaching residue (W-residue) by leveraging photovoltaic silicon kerf waste (SKW) as a silicothermic reducing agent. W-residue contains 26.2% valuable metal oxides (WO3, CoO, Nb2O5, and Ta2O5) and other refractory oxides (SiO2, TiO2, etc.), while micron-sized SKW contains 91.9% Si with a surface oxide layer. The impact of SKW addition on the silicothermic reduction process for valuable metal oxides in W-residue was investigated. Incorporating SKW and Na2CO3 flux enables valuable metal oxides from W-residue to be effectively reduced and enriched as a valuable alloy phase, with unreduced refractory oxides forming a harmless slag phase during the Na2O-SiO2-TiO2 slag refining process. This process achieved an overall recovery yield of valuable metals of 91.7%, with individual recovery yields of W, Co, and Nb exceeding 90% with the addition of 8 wt.% SKW. This innovative approach not only achieves high-value recovery from W-residue and utilization of SKW but also minimizes environmental impact through an efficient and eco-friendly recycling pathway. The strategy contributes significantly to the establishment of a resource-efficient circular economy, wherein the recovered high-value alloy phase return to the tungsten supply chain, and the harmless slag phase become raw materials for microcrystalline glass production.

Functional and structural investigation of a broadly neutralizing SARS-CoV-2 antibody.

Since its emergence, SARS-CoV-2 has been continuously evolving, hampering the effectiveness of current vaccines against COVID-19. mAbs can be used to treat patients at risk of severe COVID-19. Thus, the development of broadly protective mAbs and an understanding of the underlying protective mechanisms are of great importance. Here, we isolated mAbs from donors with breakthrough infection with Omicron subvariants using a single-B cell screening platform. We identified a mAb, O5C2, which possesses broad-spectrum neutralization and antibody-dependent cell-mediated cytotoxic activities against SARS-CoV-2 variants, including EG.5.1. Single-particle analysis by cryo-electron microscopy revealed that O5C2 targeted an unusually large epitope within the receptor-binding domain of spike protein that overlapped with the angiotensin-converting enzyme 2 binding interface. Furthermore, O5C2 effectively protected against BA.5 Omicron infection in vivo by mediating changes in transcriptomes enriched in genes involved in apoptosis and interferon responses. Our findings provide insights into the development of pan-protective mAbs against SARS-CoV-2.

The rectangular tile classification model based on Sentinel integrated images enhances grassland mapping accuracy: A case study in Ordos, China.

Arid zone grassland is a crucial component of terrestrial ecosystems and plays a significant role in ecosystem protection and soil erosion prevention. However, accurately mapping grassland spatial information in arid zones presents a great challenge. The accuracy of remote sensing grassland mapping in arid zones is affected by spectral variability caused by the highly diverse landscapes. In this study, we explored the potential of a rectangular tile classification model, constructed using the random forest algorithm and integrated images from Sentinel-1A (synthetic aperture radar imagery) and Sentinel-2 (optical imagery), to enhance the accuracy of grassland mapping in the semiarid to arid regions of Ordos, China. Monthly Sentinel-1A median value images were synthesised, and four MODIS vegetation index mean value curves (NDVI, MSAVI, NDWI and NDBI) were used to determine the optimal synthesis time window for Sentinel-2 images. Seven experimental groups, including 14 experimental schemes based on the rectangular tile classification model and the traditional global classification model, were designed. By applying the rectangular tile classification model and Sentinel-integrated images, we successfully identified and extracted grasslands. The results showed the integration of vegetation index features and texture features improved the accuracy of grassland mapping. The overall accuracy of the Sentinel-integrated images from EXP7-2 was 88.23%, which was higher than the accuracy of the single sensor Sentinel-1A (53.52%) in EXP2-2 and Sentinel-2 (86.53%) in EXP5-2. In all seven experimental groups, the rectangular tile classification model was found to improve overall accuracy (OA) by 1.20% to 13.99% compared to the traditional global classification model. This paper presents novel perspectives and guidance for improving the accuracy of remote sensing mapping for land cover classification in arid zones with highly diverse landscapes. The study presents a flexible and scalable model within the Google Earth Engine framework, which can be readily customized and implemented in various geographical locations and time periods.

C-H arylation of thiopyran derivatives with aryl halides.

A C-H arylation of thiopyran derivatives with aryl halides has been developed. Under the catalysis of Pd(OAc)2/Ag2CO3, the C-H arylation takes place at the α-position of the thiopyran ring. When dibromo-substituted compounds are used as reactants, double C-H arylations may occur on the same thiopyran ring at its α- and ß-positions.

Thiopyran-Fused Mono and Double Helicenes with Low Band Gaps via Simultaneous Ring Expansion and 6-endo Cyclizations.

Mono and double helicenes (M5, M6, D5, and D6) containing six-membered thiopyran rings have been successfully prepared via simultaneous ring expansion and 6-endo cycloisomerizations from the corresponding precursors with five-membered thiophene rings. Although D5 and D6 exhibit similar chemical structures, they demonstrate completely different helical structures because of their distinct steric clashes caused by the incorporated methyl groups. Moreover, all of the thiopyran-fused helicenes exhibit broad absorption bands covering the visible and near-infrared regions.

Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery.

BACKGROUND: Warfarin is widely used for the prevention and treatment of thrombotic events. This study aimed to examine the influence of gene polymorphisms on the early stage of warfarin therapy in patients following heart valve surgery. METHODS: Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed. RESULTS: Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability. CONCLUSION: The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.

Manipulating Intramolecular Charge Transfer and Supramolecular Interaction in D-A-D Conjugated Systems by Regioisomerization.

Three new donor-acceptor-donor (D-A-D) architecture regioisomers comprising a large planar electron-withdrawing core tribenzo[a,c,i]phenazine and two identical electron-donating triphenylamines with different substitution patterns were designed and synthesized. Employing this regioisomerization strategy, the intramolecular charge-transfer interactions are effectively tuned and result in a significant bathochromic shift of photoluminescence maximum over 100 nm, which induces the corresponding emission band extending into the near-infrared region as well as giving a high solid-state quantum yield of 25%. Meanwhile, it is found that the supramolecular interactions of this series of regioisomers with planar electron-donor pyrene are greatly affected by the substitution pattern.

Association Between Serum Anion Gap and Mortality in Critically Ill Patients with COPD in ICU: Data from the MIMIC IV Database.

Background: Serum anion gap (AG) has been proven to be associated with prognosis in critically ill patients. However, few studies have investigated the association between AG and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Objective: We hypothesized that the initial AG level would predict the mortality risk in critically ill patients with COPD. Methods: This retrospective cohort study was based on the Medical Information Mart for Intensive Care (MIMIC) IV database. We extracted demographics, vital signs, laboratory tests, comorbidity, and scoring systems from the first 24 hours after patient ICU admission. Multivariable logistic regression analysis models were used to explore the association between serum AG levels and mortality. Interaction and stratified analyses were conducted including age, gender and comorbidity. Results: A total of 5531 critically ill patients with COPD were enrolled, composed of 53.6% male and 46.4% female with a median age of 73 years. The all-cause mortality of these patients during ICU hospitalization was 13.7%. The risk of all-cause mortality increased as the AG level increased in the univariate logistic regression analysis (OR=1.13, 95% CI: 1.11-1.15, p<0.01). After adjusting for all the covariates in multivariate logistic regression analysis, the odds ratio was 1.06 (95% CI: 1.04-1.09, p<0.01). Compared with the lowest AG group Q1 (≤11mmol/L), the adjusted OR value for AG and mortality in Q2 (12-13mmol/L) was 0.89 (95% CI: 0.63-1.25, p=0.502), Q3 (14-15mmol/L) was 0.95 (95% CI: 0.68-1.34, p=0.788), and Q4 (≥16mmol/L) was 1.49 (95% CI: 1.10-2.02, p=0.009) respectively. In addition, the results of the subgroup and stratified analyses were robust. Conclusion: AG is positively related to all-cause mortality in critically ill patients with COPD.

Preparation of pH-sensitive alginate-based hydrogel by microfluidic technology for intestinal targeting drug delivery.

Hydrogel microspheres stand out in drug delivery due to their small particle size, biocompatibility and good internal stability. In this paper, pH-sensitive hydrogels are prepared by microfluidic technology for targeted drug delivery in the small intestine. A coaxial dual-channel microfluidic chip is constructed. By analyzing the effects of flow rates and three fracture stages (Rayleigh-Plateau instability crushing stage, pressure difference crushing stage and shear force crushing stage) on the size of hydrogel microspheres, the optimal control stage of the microsphere size is determined (shear force crushing stage). Based on this, the accurate control model of the hydrogel microsphere size is proposed. In addition, based on the coaxial dual channel microfluidic chip, a monolayer hydrogel microcapsule loaded with Indometacin is prepared. The core-shell hydrogel microcapsules loaded with Indometacin are prepared by an improved coaxial three channel microfluidic chip. The swelling rates of both microcapsules in simulated intestinal fluid are significantly higher than those in simulated gastric fluid. The results of in vitro simulated release experiments show that the two hydrogel microcapsules basically do not release in simulated gastric juice. In simulated intestinal fluid, single-layer hydrogel microcapsules show rapid release, while core-shell hydrogel microcapsules showed slow release. In conclusion, the alginate-based hydrogel microcapsules have good stability and pH sensitivity, and are suitable for targeted drug delivery in the small intestine.

Boosted Oxygen Kinetics of Hierarchically Mesoporous Mo2C/C for High-current-density Zn-air Battery.

The high-current-density Zn-air battery shows big prospects in next-generation energy technologies, while sluggish O2 reaction and diffusion kinetics barricade the applications. Herein, the sequential assembly is innovatively demonstrated for hierarchically mesoporous molybdenum carbides/carbon microspheres with a tunable thickness of mesoporous carbon layers (Meso-Mo2C/C-x, where x represents the thickness). The optimum Meso-Mo2C/C-14 composites (≈2 µm in diameter) are composed of mesoporous nanosheets (≈38 nm in thickness), which possess bilateral mesoporous carbon layers (≈14 nm in thickness), inner Mo2C/C layers (≈8 nm in thickness) with orthorhombic Mo2C nanoparticles (≈2 nm in diameter), a high surface area of ≈426 m2 g-1, and open mesopores (≈6.9 nm in size). Experiments and calculations corroborate the hierarchically mesoporous Mo2C/C can enhance hydrophilicity for supplying sufficient O2, accelerate oxygen reduction kinetics by highly-active Mo2C and N-doped carbon sites, and facilitate O2 diffusion kinetics over hierarchically mesopores. Therefore, Meso-Mo2C/C-14 outputs a high half-wave potential (0.88 V vs RHE) with a low Tafel slope (51 mV dec-1) for oxygen reduction. More significantly, the Zn-air battery delivers an ultrahigh power density (272 mW cm-2), and an unprecedented 100 h stability at a high-current-density condition (100 mA cm-2), which is one of the best performances.

Management Strategies for Congenital Heart Disease Comorbid with Airway Anomalies in Children.

OBJECTIVE: To assess management strategies for pediatric patients with the challenging combination of congenital heart diseases (CHDs) and airway anomalies. STUDY DESIGN: Patients diagnosed with CHD and airway anomalies in the Pediatric Cardiac Surgery Centre of Fuwai Hospital from January 2016 to December 2020 were included in this retrospective study. Patients were divided into three groups based on different management, including the conservative group, the slide group (slide tracheoplasty), and the suspension group (suspension with external stenting). Patients' data and computed tomography measurements from medical records were reviewed. RESULTS: A total of 139 patients were included in the cohort; 107 had conservative airway treatment (conservative group), 15 had slide tracheoplasty (slide group), and 17 had tracheal suspension operation (suspension group). The top three associated intracardiac anomalies were ventricular septal defect (n = 34, 24%), pulmonary artery sling (n = 22, 16%), and tetralogy of Fallot (n = 15, 11%). Compared with patients with conservative airway management (100 minutes [median], 62-152 [IQR]), the extra airway procedure prolonged cardiopulmonary bypass duration, with 202 minutes (IQR, 119-220) for the slide group and 150 minutes (IQR, 125-161) for the suspension group. Patients who underwent slide tracheoplasty required prolonged mechanical ventilation (129 minutes [median], 56-328 [IQR]). Of the total cohort, 6 in-hospital deaths, all in the conservative group, and 8 mid-to long-term deaths, with 6 in the conservative group, occurred. CONCLUSIONS: Both conservative and surgical management of CHD patients with airway anomalies have promising outcomes. Extra tracheobronchial procedures, especially the slide tracheoplasty, significantly prolonged cardiopulmonary bypass duration. Based on multidisciplinary team assessment, individualized management strategies should be developed for these patients.

Synergistic anti-tumour activity of sorafenib in combination with pegylated resveratrol is mediated by Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways.

Introduction: To investigate the inhibitory effect of sorafenib combined with PEGylated resveratrol on renal cell carcinoma (RCC) and its potential mechanism. Methods: MTT assay was used to detect the inhibitory effects of PEGylated resveratrol and sorafenib alone or combination on proliferation of RCC cells. Scratch and transwell assays were performed to examine the effects on the in vitro migration and invasion of RCC cells, respectively. The anti-tumor activity as well as splenic lymphocyte proliferation of the combination therapy was evaluated in the RCC xenograft mouse model. Western blotting method was used to detect changes in proteins involved in the antitumor efficacy related signaling pathways. Results: Inhibitory effects of PEGylated resveratrol combined with sorafenib incubation on the proliferation of Renca cells was synergistically enhanced compared with the mono-incubation group (both P < 0.01, CI < 1). Scratch and transwell assays revealed that combined incubation could significantly inhibit the migration and invasion of 786-O cells in vitro. Combined PEGylated resveratrol with sorafenib could significantly inhibit the growth of Renca renal carcinoma in mice with the tumor growth inhibition (TGI) of 85.5% and one achieved complete remission on D14, while the two monotherapies were both below 43% on D14, suggesting that current combination may have synergistic anti-renal carcinoma activity. Compared with the control group, PEGylated resveratrol combined with sorafenib in vivo promoted the proliferation of unactivated splenic lymphocytes and the proliferation of lymphocytes stimulated with concanavalin A and lipopolysaccharide. Western blotting results showed that combination therapy may suppress the growth of renal cell carcinoma by inhibiting AKT/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways. Conclusion: PEGylated resveratrol combined with sorafenib can achieve synergistic anti-RCC activity, and the mechanism may be related to the inhibition of Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways.

Incidence trends and survival of metastatic prostate cancer with bone and visceral involvement: 2010-2019 surveillance, epidemiology, and end results.

Background: The incidence of prostate cancer (PCa) has continued to increase since the US Preventive Services Task Force (USPSTF) recommendations against prostate-specific antigen (PSA)-based screening for all men in 2012, approximately half of additional diagnosed cases are advanced-stage, including regional PCa and metastatic PCa (mPCa). It is very important to investigate the shift in mPCa incidence and mPCa-related mortality risk, as the survival of mPCa remains poor. Objective: To investigate the incidence temporal trend of mPCa stratified by metastatic site, including bone and visceral metastatic involvement, and potential survival improvements. Materials: Based on the recently released Surveillance, Epidemiology, and End Results (SEER) data (2010-2019), the age-adjusted incidence rates of mPCa with bone and visceral involvement with annual percentage changes (APCs) were assessed by a joinpoint regression model in men aged 45 years and older by age and race groups, and potential recent improvements in overall survival (OS) and cancer-specific survival (CSS) were estimated by the Kaplan-Meier method and Cox regression model. Results: From 2010 to 2019, a total of 19081 (84.8%) and 3413 (15.2%) mPCa patients with bone and visceral involvement, respectively, were recorded in the SEER database. Considering all races and age groups, the incidence rate of mPCa with bone metastasis remained stable during 2017-2019 (APC, 0.9%; p=0.421) after increasing during 2010-2017 (APC, 5.8%; p<0.001). For visceral metastasis, the incidence rate increased by 12.3% (p<0.001) per year from 2010-2019. Non-Hispanic Black men have higher incidence rates than other populations, and the Non-Hispanic Black to Non-Hispanic White incidence rates ratios of mPCa declined with the greater increasing pace of incidence of Non-Hispanic White men. There was a slight improvement in both OS and CSS among men with bone and visceral metastasis involvement when comparing the 2013-2016 period to the pre-2013 period. Conclusion: Our findings show that the incidence of mPCa with bone and visceral involvement has increased in recent years and that there has been a potential improvement in survival. Future efforts are still needed to watch closely if the rising incidence trends continue.

Evidence for widespread thermal optimality of ecosystem respiration.

Ecosystem respiration (ER) is among the largest carbon fluxes between the biosphere and the atmosphere. Understanding the temperature response of ER is crucial for predicting the climate change-carbon cycle feedback. However, whether there is an apparent optimum temperature of ER ([Formula: see text]) and how it changes with temperature remain poorly understood. Here we analyse the temperature response curves of ER at 212 sites from global FLUXNET. We find that ER at 183 sites shows parabolic temperature response curves and [Formula: see text] at which ER reaches the maximum exists widely across biomes around the globe. Among the 15 biotic and abiotic variables examined, [Formula: see text] is mostly related to the optimum temperature of gross primary production (GPP, [Formula: see text]) and annual maximum daily temperature (Tmax). In addition, [Formula: see text] linearly increases with Tmax across sites and over vegetation types, suggesting its thermal adaptation. The adaptation magnitude of [Formula: see text], which is measured by the change in [Formula: see text] per unit change in Tmax, is positively correlated with the adaptation magnitude of [Formula: see text]. This study provides evidence of the widespread existence of [Formula: see text] and its thermal adaptation with Tmax across different biomes around the globe. Our findings suggest that carbon cycle models that consider the existence of [Formula: see text] and its adaptation have the potential to more realistically predict terrestrial carbon sequestration in a world with changing climate.