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Abstract Background Pancreatic cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression and immune evasion. Asperuloside (ASP) is an iridoid glycoside with potential anti-tumor properties. This study aimed to explore the molecular mechanisms of ASP on CAFs, particularly focusing on its effects on activating transcription factor 6 (ATF6), a key regulator of endoplasmic reticulum stress. Method CAFs were treated with different concentrations of ASP (0, 1, 3, and 5 mM), and the role of ATF6 was investigated by over-expressing it in CAFs. Subsequently, western blot was used to detect ATF6, α-smooth muscle actin (α-SMA), fibroblast activating protein (FAP), and vimentin protein levels in CAFs. The collagen gel contraction assay and Transwell assay were applied to evaluate the contraction and migration ability of CAFs. In addition, the interleukin (IL)-6, C–C motif chemokine ligand (CCL)-2, and C-X-C motif chemokine ligand (CXCL)-10 levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results CAFs had significantly higher expression levels of α-SMA, FAP, and vimentin compared to normal fibroblasts (NFs). ASP significantly inhibited the activation, contraction, and migration of CAFs in a concentration-dependent manner. ASP treatment also reduced the expression of cytokines (IL-6, CCL2, and CXCL10) and down-regulated ATF6 levels. Over-expression of ATF6 mitigated the inhibitory effects of ASP. Conclusion ASP exerts its anti-tumor effects by down-regulating ATF6, thereby inhibiting the activation and function of pancreatic CAFs. These findings suggest that ASP could be a promising therapeutic agent for pancreatic cancer by modulating the tumor microenvironment.

Abstract Currently approved HER2-targeting antibody-drug conjugates (ADCs) for HER2-positive breast cancer (BC) are associated with safety concerns. In this multicenter, single-arm, dose-escalation (phase 1a) and dose-expansion (phase 1b) phase 1 trial (NCT03944499), patients with HER2-expressing advanced solid tumors received FS-1502 (an anti-HER2 ADC) with a 3 + 3 design in phase 1a; patients with metastatic HER2-positive BC received FS-1502 at the recommended phase 2 dose (RP2D) in phase 1b. The primary end points were dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D for phase 1a and objective response rate (ORR) for phase 1b. A total of 150 patients with HER2-expressing solid tumors (n = 5) and BC (n = 145) were enrolled (female, n = 146, 97.3%). One DLT each was reported at 3.0 and 3.5 mg/kg; the MTD was not reached. The RP2D was 2.3 mg/kg once every 3 weeks. Five (3.3%) patients experienced pneumonitis; four (2.7%) had grade 3 reversible ocular events. Of 67 HER2-positive BC patients receiving the RP2D, the best ORR was 53.7% (95% CI, 41.1-66.0%), including PRs confirmed (confirmed ORR, 37.5%) and pending for confirmation. FS-1502 was well tolerated with limited ocular and pulmonary findings and demonstrated promising antitumor activity in HER2-positive BC patients.

In search of innovative antifungal solutions for the control of plant diseases, a series of cyanoacrylate derivatives containing naphthalene groups were designed and synthesized, and their inhibition activity against four plant pathogenic fungi was evaluated. The results of in vitro bioassay revealed that some target compounds possessed obvious antifungal effect against Fusarium graminearum. As the most prominent one, compound A2 showed a inhibition rate of 98.46 % at 10 µg/mL and an EC50 value of 0.26 µg/mL, which was close to that of the positive control phenamacril (with a inhibition rate of 100 % at 10 µg/mL and EC50 value of 0.14 µg/mL). The compound A2 also markedly inhibited the growth of F. graminearum inoculated on rice leaves at 200 μg/mL with the protective and curative efficiencies of 89.03 % and 90.91 %, respectively, which were close to that of the positive control phenamacril (with the protective and curative efficiencies of 94.54 % and 96.36 %, respectively). The observation under scanning electron microscopy and measurement of relative conductivity revealed that compound A2 caused the hyphal surface become shrunken and rough, and made the cell membrane permeability increased. Molecular docking and molecular dynamics simulation analyses showed that compound A2 interacted with the key residues in the active site of myosin-5 in a similar mode as phenamacril. These results suggested that target compounds were potential myosin-5 inhibitors, they could serve as the lead compounds for further structural optimization to develop new fungicides against F. graminearum.

Background: High circulatory lipoprotein(a) [Lp(a)] concentration promotes atherosclerosis; however, its efficacy in predicting the extent of atherosclerotic coronary heart disease (CHD) with coronary artery obstruction and major adverse cardiovascular events (MACEs) in diabetic patients remains questionable. This study aimed to examine whether elevated circulating Lp(a) levels exacerbate CHD and to assess their utility in predicting MACEs in individuals diagnosed with type 2 diabetes mellitus (T2DM). Methods: In total, 4332 patients diagnosed with T2DM who underwent coronary angiography (CAG) were included and categorized into two groups (CHD and non-CHD) based on the CAG results. We used a correlation analysis to explore the potential links between the levels of circulating Lp(a) and CHD severity. Cox regression analysis was performed to evaluate MACEs. Results: The concentrations of circulating Lp(a) were markedly elevated in the CHD group and positively correlated with disease severity. Our results indicate that elevated circulating Lp(a) is a crucial risk factor that significantly contributes to both the progression and severity of CHD. The differences between the two groups are evident in the risk of CHD occurrence [odds ratio (OR) = 1.597, 95 % confidence interval (CI): 1.354–1.893, p

Public cell culture platform is an important facility in laboratory animal facilities, providing essential support for scientific research such as the development of animal tumor disease models and transgenic animals. By establishing a public cell culture experimental platform, laboratory animal centers can effectively integrate experimental animals and cell culture resources, optimizing the allocation of scientific research resources to facilitate better research outcomes. The majority of cells cultured in these platforms are used for animal experiments. Contamination or quality issues in these cells not only affect experimental results but also jeopardize the health of experimental animals, potentially leading to microbial infections and contamination of entire animal facilities. Therefore, public cell culture laboratories within experimental animal facilities impose stricter quality control measures than conventional cell culture rooms. This study takes the public cell culture platform at the Laboratory Animal Center of Shanghai Jiao Tong University as a case study to discuss management experiences, focusing on facility maintenance and management, personnel management and quality control of cell biological risk. The aim is to provide useful reference for the management of public cell culture laboratories in experimental animal facilities and other institutions.

Abstract Background Laparoscopic surgery has been endorsed by clinical guidelines for colon cancer, but not for rectal cancer on account of unapproved oncologic equivalence with open surgery. Aims We started this largest‐to‐date meta‐analysis to comprehensively evaluate the safety and efficacy of laparoscopy in the treatment of rectal cancer compared with open surgery. Materials & Methods Both randomized and nonrandomized controlled trials comparing laparoscopic proctectomy and open surgery between January 1990 and March 2020 were searched in PubMed, Cochrane Library and Embase Databases (PROSPERO registration number CRD42020211718). The data of intraoperative, pathological, postoperative and survival outcomes were compared between two groups. Results Twenty RCTs and 93 NRCTs including 216,615 patients fulfilled the inclusion criteria, with 48,888 patients received laparoscopic surgery and 167,727 patients underwent open surgery. Compared with open surgery, laparoscopic surgery group showed faster recovery, less complications and decreased mortality within 30 days. The positive rate of circumferential margin (RR = 0.79, 95% CI: 0.72 to 0.85, p

Introduction: Urban resilience is suffering from the challenges of climate change. The increasing volatility of climate change and its impact on urban resilience necessitates a deeper understanding of how internal organizational behaviors can contribute toward sustainable city development. Pro-environmental behavior is one of the important methods of affecting climate change and enhancing urban resilience. This study investigates how employee participation in corporate social responsibility activities promotes pro-environmental behavior and its mechanism.Methods: This research was conducted an online survey of 262 employees from 22 industries in mainland China. To mitigate the bias arising from self-reported assessments by the employees, the data were collected at two time points.Results: Empirical research reveals that employee participation in corporate social responsibility is positively related to employee pro-environmental behavior; these empirical findings not only support how psychological ownership mediates the link between corporate social responsibility participation and pro-environmental behavior but also indicate how employee engagement acts as an intermediary mechanism in enhancing this positive association. Moreover, the chain mediation effect of psychological ownership and employee engagement in the positive link between corporate social responsibility participation and pro-environmental behavior is found to be significant.Discussion: These findings not only enrich the effects of the mechanism of corporate social responsibility participation on employee behavior by introducing new theoretical perspectives but also deepen understanding of the antecedents promoting employee pro-environmental behavior, thereby contributing to the improvement of urban resilience in the face of climate change.

Abstract Micro-sized silicon anodes can significantly increase the energy density of lithium-ion batteries with low cost. However, the large silicon volume changes during cycling cause cracks for both organic-inorganic interphases and silicon particles. The liquid electrolytes further penetrate the cracked silicon particles and reform the interphases, resulting in huge electrode swelling and quick capacity decay. Here we resolve these challenges by designing a high-voltage electrolyte that forms silicon-phobic interphases with weak bonding to lithium-silicon alloys. The designed electrolyte enables micro-sized silicon anodes (5 µm, 4.1 mAh cm−2) to achieve a Coulombic efficiency of 99.8% and capacity of 2175 mAh g−1 for >250 cycles and enable 100 mAh LiNi0.8Co0.15Al0.05O2 pouch full cells to deliver a high capacity of 172 mAh g−1 for 120 cycles with Coulombic efficiency of >99.9%. The high-voltage electrolytes that are capable of forming silicon-phobic interphases pave new ways for the commercialization of lithium-ion batteries using micro-sized silicon anodes.

Extracts of Stevia rebaudiana Bertoni plant leaves contain a mixture of diterpene glycosides which possess high sweetness and are used as non-caloric sweeteners in foods and beverages. One of the most abundant of these steviol glycosides is Rebaudioside C (Reb C), which bears one esterified β-D-glucose and one glycosidically linked α-L-rhamnosyl-(1→2)-[β-D-glucosyl-(1→4)]-D-glucose trisaccharide. In this work, we isolated Reb C from commercial Stevia extracts using an orthogonal normal-phase × reversed-phase purification strategy. We then demonstrated that Reb C could be used as a donor substrate for enzymatic trans glycosylation reactions using chemically synthesized 1-deoxy-1-fluoro-D-glucose and 1-deoxy-1-fluoro-D-galactose donors and two engineered glycosynthases derived from Agrobacterium and Streptomyces β-glycosidases. This chemoenzymatic glucosylation/galactosylation strategy may be of use to extend the current repertoire of steviol glycosides analogues for analysis or the sensory evaluation of these novel steviol glycosides.

Abstract Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs. Results Circulating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group [554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p

AbstractContext Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases.Objective The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development.Materials and methods BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin.Results Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses.Discussion and conclusions The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD.

Abstract Background and Objectives This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. Methods This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80–1.25. Results In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (C max; GMR: 109.1% [90% CI 103.1–115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration–time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3–110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6–110.6]). In both groups, the median time to maximum plasma concentration (t max) was around 6 h and mean plasma half-life (t ½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration. Conclusions A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs.

AIM: To investigate the changes and correlation of retinal nerve fiber layer(RNFL)and macular retinal thickness in children with anisometropic amblyopia.METHODS: A total of 159 cases(159 eyes)children with anisometropic amblyopia treated in our ophthalmology department from October 2020 to June 2021 were selected as the study group, and 159 cases(159 eyes)children with normal vision who examined in the ophthalmology department of our hospital in the same period and age group were selected as the control group. The study group received traditional comprehensive training combined with 4D visual training for amblyopia based on refractive correction and covering of healthy eyes. The RNFL and macular retinal thickness before and after treatment between the study group and the control group was compared, and the correlation between RNFL and macular retinal thickness before treatment in the study group was analyzed.RESULTS: The RNFL thickness of average, upper, lower, nasal and temporal in the study group before and after 3mo of treatment was higher than those of the control group, and the RNFL thickness of average, upper, lower, nasal and temporal before treatment in the study group was higher than those after 3mo of treatment(P

Objectives: Our goal in this study was to determine 1) whether there are any differences in clinical characteristics between Chinese and Western patients with aortic dissection (AD), and 2) the mortality rate of AD patients in the emergency department (ED) and identify the risk predictors for death.Methods: We retrospectively analyzed patients who were diagnosed with AD and admitted to our ED between September 1, 2017–August 31, 2020. Data on age, gender, clinical manifestation, medical history, routine blood tests, liver and kidney function, coagulation, myocardial enzymology, and mortality were collected.Results: We enrolled 535 AD patients (422 men and 113 women) with a mean age of 54.7±14.1 years. Type A AD constituted 40% of the total number of AD cases, while type B AD constituted 60%. The proportion of those who were females, 10-92 years, with type A AD, and hypertension in the Chinese population was lower than that in the Western population (P

This study investigated the distribution of sedimentary phosphorus (P) species along an area of a rapid current at the southern coast of Zhoushan Island. The objective of this study was to improve the understanding of P cycling in a zone of rapid water cycling. Results showed that the average percentage of each P form to total P (TP) was in the following order: apatite P (Ca-P; 52%) was found in the most abundant, followed by organic P (OP; 16%), exchangeable-P (Ex-P; 14%), detrital P (De-P; 11%), and iron-bound P (Fe-P; 7%). Ca-P showed a trend of an increasing concentration from a location at the west (ZS1 has mean Ca-P = 45.6 mg kg−1) toward the east (ZS2 has mean Ca-P = 82.69 mg kg−1) and south-east (ZS3 has mean Ca-P = 82.17 mg kg−1); De-P also increased from 15.12 mg kg−1 at ZS1 to 22.53 mg kg−1 at ZS2 and 27.45 mg kg−1 at ZS3, but the three bioavailable P species, OP, Ex-P, and Fe-P, decreased from the west toward the east of the coastal area. Results along the cores showed the occurrences of sediment P adsorption and release throughout the time span from the 1930s to the present, with an overall trend of decreasing Ca-P and TP from the bottom to surface sediments. There was a tendency of Ca-P formation at the expense of Ex-P and OP release during transport and organic matter decomposition. The likely impact of climate change in the coastal zone would be an increased temperature resulting in elevated organic matter decomposition and P release.

As an important part of die steels, hot-work die steels are mainly used to manufacture molds made of solid metal or high-temperature liquid metal from heating to recrystallization temperature. In view of the requirements for mechanical properties and service life for hot-work die steel, it is conducive to improve the thermal fatigue resistance, wear resistance, and oxidation resistance of hot work die steel. In this review, the main failure modes of hot-work die steel were analyzed. Four traditional methods of strengthening and toughening die steel were summarized, including optimizing alloying elements, electroslag remelting, increasing the forging ratio, and heat treatment process enhancement. A new nano-strengthening method was introduced that aimed to refine the microstructure of hot-work abrasive steel and improve its service performance by adding nanoparticles into molten steel to achieve uniform dispersion. This review provides an overview to improve the service performance and service life of hot work die steel.

Abstract Introduction Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). Methods This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. Results This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. Conclusion Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

This study examines the impact of the Latin American Integrated Market (MILA for its Spanish acronym) on investment efficiency from 2003 to 2020. Our research suggests that MILA affects the efficiency of investment decisions by reducing information asymmetry and the agency problem. We present compelling empirical evidence that the impact of MILA on enhancing investment efficiency is especially pronounced in the over-investment problem. Furthermore, the mediation analysis reveals that firms listed on MILA stock exchanges have increased the efficiency of their investments, a result attributable partly to enhanced financial reporting quality. We employ difference-in-difference analysis to address the possibility of endogeneity. Our findings are validated by the fact that, compared with control firms, treatment firms improve their investment efficiency and mitigate the over-investment problem, thereby validating our findings.

In this reported study, the density functional theory (DFT) was used at the (U)B3LYP/6-311G(d,p) level to investigate the stabilization process of the nitrate ester plasticized polyether propellant (NEPE). Molecular simulations were conducted of the reaction that generates NO2, the autocatalytic and aging reaction triggered by the NO2, and the nitrogen dioxide absorption reaction of the stabilizers during the propellent stabilization process. These simulations were derived using the transition-state theory (TST) and variational transition-state theory (VTST). The simulation results suggested that the stabilization of the NEPE propellant consisted of three stages. First, heat and NO2 were generated during the denitrification reaction of nitroglycerine (NG) and 1,2,4-butanetriol trinitrate(BTTN) in the NEPE propellant. Second, nitroso products were generated by the reactions of N-Methyl-4-nitroaniline (MNA) and 2-nitrodiphenylamine (2NDPA) with NO2. Third, the stabilizers were exhausted and the autocatalytic reaction of NG and BTTN and the aging reaction of polyethylene glycol (PEG) were triggered by the heat and NO2 generated in the first stage. By comparing the energy barriers of the various reactions, it was found that the NO2 generated from the denitrification reaction significantly reduced the reaction energy barrier to 105.56–126.32 kJ/mol, also increased the reaction rate constant, and decreased the thermal stability and energetic properties of the NEPE propellant. In addition, the NO2 also weakened the mechanical properties of the NEPE propellant by attacking the –CH2 groups and the O atoms in the PEG molecular chain. The energy barriers of the reactions of MNA and 2NDPA with NO2 (94.61–133.61 kJ/mol) were lower than those of the autocatalytic and decomposition reactions of NG, BTTN, and the aging reactions of PEG (160.30–279.46 kJ/mol). This indicated that, by eliminating NO2, the stabilizer in the NEPE propellant can effectively prevent NO2 from reacting with the NG, BTTN, and PEG in the NEPE propellant. Consequently, this would help maintain the energy and mechanical properties of the NEPE propellant, thereby improving its thermal stability.

Abstract Background Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. Methods This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. Results Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. Conclusions FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. Trial registration ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

Natural and geological environmental conditions have an important impact on the planning and construction of sponge cities. This paper analyzes geological factors that influence the usage of natural sponge bodies, taking the Shuanghe lake district of Zhengzhou airport zone as an example. An evaluation system with seven factors has been established and the weights of these factors are determined using the analytic hierarchy process (AHP) method. Overlay analysis is then carried out on all factors using GIS to evaluate the geological suitability of the construction of the sponge city. The results show that geologically suitable area for city construction in Shuanghe lake district accounts for 12.3%, relatively suitable area accounts for 76.1%, and relatively unsuitable area accounts for 11.6%. For suitable and relatively suitable areas, we should make full use of the advantages of surface infiltration, vadose zone transportation and aquifer storage to build a sponge city infrastructure with geological engineering as the main component, supplemented by engineering measures such as surface water storage and drainage, and jointly establish a sustainable urban hydrological cycle. For less suitable areas, artificial rain and flood control works, such as roof garden, should be considered. The findings of this paper can serve as an important reference for sponge city planning and construction not only in the research area but also in other regions with similar geological conditions.

Background. Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods. This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30 mg as single dose, or 50 mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4 : 1 ratio. Results. 59 healthy volunteers received tenapanor 10 mg (n = 12 Chinese), 30 mg (n = 12 Chinese), or 50 mg (n = 12 (Chinese), n = 11 (Caucasian)) or placebo (n = 12, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50 mg) of Chinese subjects, the mean Cmax, AUC0-t, and AUC0-∞ of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The Cmax accumulation ratio was 1.55 to 6.92 after 50 mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50 mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion. Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.