Nonwoven fiber meshes for oxygen sensing.

Accurate oxygen sensing and cost-effective fabrication are crucial for the adoption of wearable devices inside and outside the clinical setting. Here we introduce a simple strategy to create nonwoven polymeric fibrous mats for a notable contribution towards addressing this need. Although morphological manipulation of polymers for cell culture proliferation is commonplace, especially in the field of regenerative medicine, non-woven structures have not been used for oxygen sensing. We used an airbrush spraying, i.e. solution blowing, to obtain nonwoven fiber meshes embedded with a phosphorescent dye. The fibers serve as a polymer host for the phosphorescent dye and are shown to be non-cytotoxic. Different composite fibrous meshes were prepared and favorable mechanical and oxygen-sensing properties were demonstrated. A Young's modulus of 9.8 MPa was achieved and the maximum oxygen sensitivity improved by a factor of ∼2.9 compared to simple drop cast film. The fibers were also coated with silicone rubbers to produce mechanically robust sensing films. This reduced the sensing performance but improved flexibility and mechanical properties. Lastly, we are able to capture oxygen concentration maps via colorimetry using a smartphone camera, which should offer unique advantages in wider usage. Overall, the introduced composite fiber meshes show a potential to significantly improve cell cultures and healthcare monitoring via absolute oxygen sensing.

The Effects of Cranberry Consumption on Glycemic and Lipid Profiles in Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This study aims to update the evidence and clarify whether cranberry possesses lipid-lowering and hypoglycemic properties in humans. PubMed, Web of Science, and Scopus were searched to identify relevant articles published up to December 2023. In total, 3145 publications were reviewed and 16 of them were included for qualitative synthesis and meta-analysis. Stata 15.0 and Review Manager 5.4 were applied for statistical analyses. The results revealed a significant decrease in the total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C) (MD = -0.24; 95% CI: -0.45, -0.04; peffect = 0.02) and homeostasis model assessment of insulin resistance (HOMA-IR) (MD = -0.59; 95% CI: -1.05, -0.14; peffect = 0.01) with cranberry consumption. However, it did not influence total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and fasting insulin. In subgroup analysis, cranberry consumption in dried form (capsules, powder, and tablets) was found to significantly decrease the fasting insulin level (three studies, one hundred sixty-five participants, MD = -2.16; 95% CI: -4.24, -0.07; peffect = 0.04), while intervention duration, health conditions, and dosage of polyphenols and anthocyanins had no impact on blood lipid and glycemic parameters. In summary, cranberry might have potential benefits in regulating lipid and glucose profiles.

Evolution of volatile compounds of baked dried tofu during catalytic infrared baking process and their correlation with relevant physicochemical properties.

BACKGROUND: Energy-saving and low-carbon baking processes, as well as the need to determine the flavor-forming mechanisms of baked dried tofu, are becoming increasingly necessary. The application of emerging catalytic infrared radiation (CIR) technology in baking of dried tofu is considered of high interest due to the low energy consumption and high baking efficiency compared to traditional baking methods. Hence, this study aimed to investigate the evolution of aroma compounds in baked dried tofu during the CIR baking process and reveal relevant relationships between physical qualities, potential flavor precursors and key volatile compounds. RESULTS: The results showed that the surface color of dried tofu gradually turned an appetizing golden yellow color during the rapid heating process, caused by the uniform infrared radiation from the radiant emitters. Meanwhile, the moisture of dried tofu experienced minimal reduction and the hardness of dried tofu gradually increased with the formation of crust on the surface. In addition, 49 volatile compounds were identified by headspace solid-phase microextraction-gas chromatography-mass spectrometry and 13 substances - 1-hexanol, 1-octen-3-ol, 1-pentanol, heptanal, nonanal, hexanal, (E,E)-2,4-decadienal, (E,Z)-2,4-decadienal, octanal, (E)-2-octenal, (E)-2-nonenal, 2-heptanone and 2-pentylfuran - were confirmed as key aroma compounds. Moreover, the amino acids aspartic acid, glutamic acid, isoleucine, lysine and arginine, and the fatty acids butyric, caprylic, capric, tridecanoic, stearic, oleic and linolenic were responsible for the unique flavor of CIR-baked dried tofu. CONCLUSION: Consequently, the findings can provide a scientific basis for manufacturers to achieve precise quality control and large-scale production of CIR-baked dried tofu products. © 2024 Society of Chemical Industry.

Developing the E. coli platform for efficient production of UMP-derived chemicals.

5-Methyluridine (5-MU) is a prominent intermediate for industrial synthesis of several antiviral-drugs, however, its availability over the past decades has overwhelmingly relied on chemical and enzymatic strategies. Here, we have realized efficient production of 5-MU in E. coli, for the first time, via a designer artificial pathway consisting of a two-enzyme cascade (UMP 5-methylase and phosphatase). More importantly, we have engineered the E. coli cell factory to boost 5-MU production by systematic evaluation of multiple strategies, and as a proof of concept, we have further developed an antibiotic-free fermentation strategy to realize 5-MU production (10.71 g/L) in E. coli MB229 (a ΔthyA strain). Remarkably, we have also established a versatile and robust platform with exploitation of the engineered E. coli for efficient production of diversified UMP-derived chemicals. This study paves the way for future engineering of E. coli as a synthetic biology platform for acceleratively accessing UMP-derived chemical diversities.

Isoalantolactone exerts anti-melanoma effects via inhibiting PI3K/AKT/mTOR and STAT3 signaling in cell and mouse models.

BACKGROUND AND AIM: Although the anti-cancer activity of isoalantolactone (IATL) has been extensively studied, the anti-melanoma effects of IATL are still unknown. Here, we have investigated the anti-melanoma effects and mechanism of action of IATL. MTT and crystal violet staining assays were performed to detect the inhibitory effect of IATL on melanoma cell viability. Apoptosis and cell cycle arrest induced by IATL were examined using flow cytometry. The molecular mechanism of IATL was explored by Western blotting, confocal microscope analysis, molecular docking, and cellular thermal shift assay (CETSA). A B16F10 allograft mouse model was constructed to determine the anti-melanoma effects of IATL in vivo. The results showed that IATL exerted anti-melanoma effects in vitro and in vivo. IATL induced cytoprotective autophagy in melanoma cells by inhibiting the PI3K/AKT/mTOR signaling. Moreover, IATL inhibited STAT3 activation both in melanoma cells and allograft tumors not only by binding to the SH2 domain of STAT3 but also by suppressing the activity of its upstream kinase Src. These findings demonstrate that IATL exerts anti-melanoma effects via inhibiting the STAT3 and PI3K/AKT/mTOR signaling pathways, and provides a pharmacological basis for developing IATL as a novel phytotherapeutic agent for treating melanoma clinically.

Predictors of Myelosuppression for Patients with Head and Neck Squamous Cell Carcinoma After Induction Chemotherapy.

Background: Induction chemotherapy (ICT) has become an initial treatment for head and neck squamous cell carcinoma (HNSCC). However, myelosuppression, an unavoidable side effect of ICT, significantly impacts follow-up treatment and prognosis. The main objective of this study is to identify the risk factors and predictors of myelosuppression and its different severity after ICT for ICT. Methods: We retrospectively reviewed medical records of 102 patients with hypopharyngeal cancer or oropharyngeal cancer who received initial ICT from 2013 to 2022. Univariate and multivariate logistic regression analyses were performed to identify risk factors for myelosuppression. Receiver-operating characteristic (ROC) curves were generated using the results of multiple logistic regression analysis to identify data with the highest sensitivity and lowest false-negative rate. Results: Pretreatment lymphocyte count (PLC) and the pretreatment platelet count (PPC) were identified as independent risk factors of myelosuppression (P < .05). Pretreatment hemoglobin count (PHC) was an independent risk factor for predicting myelosuppression in patients with grades III to IV disease. Patients with myelosuppression after ICT are more sensitive to chemotherapy. Conclusions: The PLC and PPC predicted myelosuppression in patients with HNSCC-administered ICT, and the PHC predicted grades III to IV myelosuppression. Myelosuppressed patients were more chemosensitive after ICT.

Concentration-dependent effects of lithium on Daphnia magna: Life-history profiles and integrated biomarker response implementation.

The growing use of lithium (Li) in industrial and energy applications and increasing demand worldwide has inevitably resulted in its wide dispersal, representing a significant threat to aquatic systems. Unfortunately, as a ubiquitous emerging contaminant, the comprehensive toxicological information regarding Li at multifarious levels is limited. To diminish this gap, this work was focused to explore Li-induced cascading effects on Daphnia magna as a key species in freshwater ecosystems. Specifically, the organisms were chronically exposed to gradient Li concentrations with emphasis on characterizing life-history traits from individual to population scale, primarily as observed by a markedly concentration-dependent decrease along exposure gradients. In parallel, a robust set of biomarkers relating to energy reserves, antioxidant and biotransformation enzymes, cellular damage, ionoregulation and neurotoxicity were assayed for further understanding potential underlying mechanisms. As a result, biomarker alterations were characterized by significant decreases in energy storage and enzymatic profiles of antioxidant and biotransformation systems, not only triggering an imbalance between reactive oxygen species (ROS) generation and elimination under Li exposure, but compromising the fecundity fitness of phenotypical costs. In contrast, malondialdehyde (MDA) levels were remarkably enhanced as a consequence of inefficient antioxidant and biotransformation capacity leading to lipid peroxidation (LPO). Additionally, Li exerted a dose-dependent biphasic effect on the activities of superoxide dismutase (SOD), Na+,K+-ATPase and acetylcholinesterase (AChE) by interfering with inherent balance. In terms of responsive patterns and dose-effect trends, the integrated biomarker response indices (IBRv2) and star plots were consistent with the differences in biomarker profiles, not only presenting comprehensively biological effects in a visualized form, but signaling the importance of progressive induced changes in an integrative way. Overall, these findings highlighted the need for elucidating Li-produced impacts from a comprehensive perspective, providing valuable insights into better understanding the toxicity of Li in relation to aquatic ecosystem functioning and ecological relevance.

Unlocking hormesis and toxic effects induced by cadmium in Polygonatum cyrtonema Hua based on morphology, physiology and metabolomics.

Traditional Chinese medicine materials (TCMMs) are widely planted and used, while cadmium (Cd) is a widespread pollutant that poses a potential risk to plant growth and human health. However, studies on the influences of Cd on TCMMs have been limited. Our study aims to reveal the antioxidation-related detoxification mechanism of Polygonatum cyrtonema Hua under Cd stress based on physiology and metabolomics. The results showed that Cd0.5 (total Cd: 0.91 mg/kg; effective Cd: 0.45 mg/kg) induced hormesis on the biomass of roots, tubers and aboveground parts with increases of 22.88%, 27.12% and 17.02%, respectively, and significantly increased the flavonoids content by 57.45%. Additionally, the metabolism of caffeine, glutamine, arginine and purine was upregulated to induce hormesis in Cd0.5, which enhanced the synthesis of resistant substances such as spermidine, choline, IAA and saponins. Under Cd2 stress, choline and IAA decreased, and fatty acid metabolites (such as peanut acid and linoleic acid) and 8-hydroxyguanosine increased in response to oxidative damage, resulting in a significant biomass decrease. Our findings further reveal the metabolic process of detoxification by antioxidants and excessive Cd damage in TCMMs, deepen the understanding of detoxification mechanisms related to antioxidation, and enrich the relevant theories of hormesis induced by Cd.

One-step synthesis of iron and nitrogen co-doped porous biochar for efficient removal of tetracycline from water: Adsorption performance and fixed-bed column.

Here, Fe/N co-doped porous biochars (FeNKBCs) were obtained by grinding corncob, CH3COOK, FeCl3·6H2O, and C3H6N6 via one-step synthesis and were applied to remove antibiotics from wastewater. Notably, CH3COOK had an excellent porous activation ability. The developed nanotubular structure of Fe1N2KBC had a high pore volume (Vtotal) (1.2131 cm3/g) and specific surface areas (SSA) (2083.54 m2/g), which showed outstanding sorption abilities for TC (764.35 mg/g), OTC (560.82 mg/g), SMX (291.45 mg/g), and SMT (354.65 mg/g). The adsorption process of TC was controlled by chemisorption. Moreover, Fe1N2KBC has an excellent dynamic adsorption performance (620.14 mg/g) in a fixed-bed column. The properties of SSA, Vtotal, and the content of graphite N and Fe-N were positively correlated with TC adsorption capacity. The high performance of TC removal was related to π-π stacking, pore-filling, hydrogen bond, and electrostatic interaction. Fe1N2KBC possessed stable sorption amounts in pH 2-12 and actual water, and well reuse performance. The results of this work present an effective preparation method of Fe/N porous biochar for TC-contaminated water remediation.

Palladium-Catalyzed Deuteration of Arylketone Oxime Ethers.

We report herein the development of palladium-catalyzed deacylative deuteration of arylketone oxime ethers. This protocol features excellent functional group tolerance, heterocyclic compatibility, and high deuterium incorporation levels. Regioselective deuteration of some biologically important drugs and natural products are showcased via Friedel-Crafts acylation and subsequent deacylative deuteration. Vicinal meta-C-H bond functionalization (including fluorination, arylation, and alkylation) and para-C-H bond deuteration of electro-rich arenes are realized by using the ketone as both directing group and leaving group, which is distinct from aryl halide in conventional dehalogenative deuteration.

Drought-resistant and water-retaining tobermorite/starch composite hydrogel for the remediation of cadmium-contaminated soil.

The objective of this work is utilizing fly ash to synthesize tobermorite (TOB) with a higher specific surface area and layered structure, and incorporating it into the starch/acrylic acid network to boost the drought resistance, water retention and heavy metal adsorption properties. The water absorption and water retention performance and cadmium adsorption characteristics of tobermorite/leftover rice-based composite hydrogel (TOB@LR-CH) were evaluated by water absorption swelling test, soil evaporation test and batch adsorption experiment. By adjusting the addition of TOB and other synthesized conditions, the swelling property (from 114.80 g/g to 322.64 g/g), water retention (71.80 %, 144 h) and Cd2+ adsorption characteristics (up to 591.36 mg/g) were significantly enhanced. Adding a moderate amount of TOB (2 wt%) provided the most uniform tobermorite dispersion during synthesis, and TOB2@LR-CH exhibited the most stable three-dimensional network and highest proportion of effective TOB. The adsorption behavior of cadmium on TOB2@LR-CH was more consistent with the pseudo-second-order kinetics and Langmuir isotherm models. Additionally, the regeneration test results displayed that the adsorption removal rate of cadmium by TOB2@LR-CH adsorbent remained stable after 5 cycles. This study demonstrates that TOB@LR-CH has good water absorption and water retention potential in arid and semi-arid soils, and also has potential application prospects in remediating Cd(II)-contaminated soil.

Safe utilization evaluation of two typical traditional Chinese medicinal materials in Cd-contaminated soil based on the analysis of Cd transfer and AHP model.

Due to the increasing scarcity of wild resources, most traditional Chinese medicinal materials (TCMMs) in the market are produced via artificial cultivation. The widespread pollution of cadmium (Cd) in soil limits the safe cultivation and use of TCMMs. This study investigated Cd accumulation, distribution, and the medicinal component content under simulated field conditions to clarify the differences in the Cd absorption, transfer and detoxification mechanisms of Polygonatum cyrtonema Hua and Bletilla striata, and provide the preliminary safe utilization conditions of TCMMs based on the analytic hierarchy process (AHP). The results showed that the Cd content of P. cyrtonema Hua was lower than the safety threshold under a high soil Cd concentration of 0.91 mg/kg (Cd-L), while B. striata was safe only at a low Cd concentration of 0.25 mg/kg (CK). Cd at 0.91 mg/kg induced hormesis affecting the net increase in biomass and medicinal component content for both TCMMs, while P. cyrtonema Hua showed better potential for safe utilization. Additionally, P. cyrtonema Hua had stronger resistance to Cd stress, exhibiting superior characteristics for synergistic absorption of Cd with mineral elements, transfer to nonmedical part and safer fixation forms in subcellular components. In contrast, B. striata showed insufficient Cd tolerance, and Cd was easily accumulated in organelles to inhibit plant growth. Our findings may attract more attention to the safe cultivation of TCMMs and provide insight into guidance for the safe utilization of slightly Cd-contaminated soil.

Comparison of diagnosis-related group based reimbursement and case-mix index within hospitalized patients before and after modified malnutrition diagnosis.

BACKGROUND AND OBJECTIVES: Lack of professional and accurate diagnosis of malnutrition led to a reduction in Diagnosis Related Group (DRG) payment and a decrease in Case-Mix Index (CMI). The aim of this study was to explore the effects of adding a proper nutritional diagnosis and modifying complication groups on DRG payment and CMI. METHODS AND STUDY DESIGN: Retrospective analysis was performed on patients ad-mitted to the hospital from January to June 2022 who had received a nutritional assessment. Patients were diagnosed as well-nourished, mild malnutrition, moderate malnutrition or severe malnutrition according to patient-generated subjective global assessment (PG-SGA) scores within 24 hours of admission. CMI and DRG hospital internal control standards were recalculated and compared with the original values. RESULTS: A total of 254 patients were enrolled, including 40 patients with mild malnutrition, 74 patients with moderate malnutrition and 122 patients with severe malnutrition. Of all subjects, 111 changed complication groups. The median of the DRG hospital internal control standard (12006.09 vs. 13797.19, p=0.01) and the median of CMI (0.91 vs. 1.04, p=0.026) were significantly higher than those before the diagnostic change. In patients with inflammatory bowel disease (IBD), the CMI value, hospital control standard of DRG, and the classification of DRG were significantly different from those before diagnosis revision (p<0.001). CONCLUSIONS: Fully identification and correct coding of malnutrition cases are conducive for hospitals to receive appropriate DRG compensation, and further contribute to the improvement of medical quality and the economic sustain-ability of hospitals.

Response of phytoplankton community structure to environmental changes in the coastal areas of northern China.

In this study, we analyzed high-frequency data pertaining to phytoplankton and environmental factors in Jiaozhou Bay from December 10, 2004, to December 10, 2005 and from July 26, 2020, to August 1, 2021. Compared with 2004-2005, the abundance of phytoplankton during 2020-2021 presented a "two-peak pattern" of annual variation, and the number of species decreased significantly. The ecological types were dominated by eurythermal species, while cold-water species declined. The overall abundance showed a downward trend, and the peak period moved to a time with lower water temperature. This could be attributed to the increase in sea surface temperature. The increase in water temperature and intensification of eutrophication made the emergence of dominant species more inclined to be single; the diversity and stability of the community structure decreased. Generalized additive model (GAM) and network analysis showed that temperature was the main driving factor influencing the phytoplankton community structure, especially during the peak period. In addition, nitrogen and phosphorus were important factors influencing species composition and competitive advantage of phytoplankton.

Iron oxide nanoparticles induce ferroptosis via the autophagic pathway by synergistic bundling with paclitaxel.

In recent years, inhibiting tumor cell activity by triggering cell ferroptosis has become a research hotspot. The development of generic targeted nanotherapeutics might bring new ideas for non­invasive applications. Currently, the potential mechanism underlying the universal application of paclitaxel (PTX)­loaded iron oxide nanoparticles (IONP@PTX) to different types of tumors is unclear. The present study aimed to prepare IONP@PTX for targeted cancer therapy and further explore the potential mechanisms underlying the inhibitory effects of this material on the NCI­H446 human small cell lung cancer and brain M059K malignant glioblastoma cell lines. First, a CCK­8 assay was performed to determine cell viability, and then the combination index for evaluating drug combination interaction effect was evaluated. Intracellular reactive oxygen species (ROS) and lipid peroxidation levels were monitored using a DCFH­DA fluorescent probe and a C11­BODIPY™ fluorescent probe, respectively. Furthermore, western blotting assay was performed to determine the expression of autophagy­ and iron death­related proteins. The experimental results showed that, compared with either IONP monotherapy, PTX monotherapy, or IONP + PTX, IONP@PTX exerted a synergistic effect on the viability of both cell types, with significantly increased total iron ion concentration, ROS levels and lipid peroxidation levels. IONP@PTX significantly increased the expression of autophagy­related proteins Beclin 1 and histone deacetylase 6 (HDAC6) in both cell lines (P<0.05), increased the expression of light chain 3 (LC3)­II/I in NCI­H446 cells (P<0.05) and decreased that of sequestosome1 (p62) in M059K cells (P<0.05). Moreover, the addition of rapamycin enhanced the IONP@PTX­induced the upregulation of Beclin 1, LC3­II/I and HDAC6 and the downregulation of mTORC1 protein in both cell lines (P<0.05). Moreover, rapamycin enhanced the IONP@PTX­induced downregulation of p62 protein in NCI­H446 cells (P<0.05), suggesting that IONP@PTX induces ferroptosis, most likely through autophagy. Collectively, the present findings show that IONP works synergistically with PTX to induce ferroptosis via the autophagic pathway.

Selenium improves the medicinal safety and quality of Bletilla striata by promoting the fixation of cadmium in root: Pot and field experiments.

Soil cadmium (Cd) pollution poses a considerable threat to the safe production of traditional Chinese medicine (TCM) in China. The tubers of Bletilla striata, a precious TCM, are widely used to treat various ailments. However, the medicinal safety and quality of tubers are significantly affected by high Cd accumulation. While selenium (Se) is known to reduce Cd concentration in traditional crops, its impact on Cd content in medicinal parts and overall quality remains underexplored. To bridge the gap, a pot experiment and field validation were conducted to determine the effectiveness of foliar Se application. The results revealed that Se effectively counteracted Cd damage. Compared to Cd treatment alone, Se at 1.5 mg L-1 significantly decreased Cd content by 46.33 %, increased the biomass by 21.48 %, and raised the total phenolic, flavonoid, saponin, and polysaccharide contents by 46.31 %, 30.46 %, 27.08 %, and 29.01 %, respectively, in tubers. Furthermore, this study explored the mechanism of Se action. Se facilitated Cd accumulation in root cell walls and soluble fractions, enhanced the synthesis of phytochelatins (PC), and stored them in the form of PC-Cd complexes. These findings have profound implications for the cultivation of TCM, ensuring its safety, and promoting sustainable agricultural practices.

Design and Demonstration of an In-Plane Micro-Optical-Electro-Mechanical-System Accelerometer Based on Talbot Effect of Dual-Layer Gratings.

An ultrasensitive single-axis in-plane micro-optical-electro-mechanical-system (MOEMS) accelerometer based on the Talbot effect of dual-layer gratings is proposed. Based on the Talbot effect of gratings, the acceleration can be converted into the variation of diffraction intensity, thus changing the voltage signal of photodetectors. We investigated and optimized the design of the mechanical structure; the resonant frequency of the accelerometer is 1878.9 Hz and the mechanical sensitivity is 0.14 µm/g. And the optical grating parameters have also optimized with a period of 4 µm and a grating interval of 10 µm. The experimental results demonstrated that the in-plane MOEMS accelerometer with an optimal design achieved an acceleration sensitivity of 0.74 V/g (with better than 0.4% nonlinearity), a bias stability of 75 µg and an acceleration resolution of 2.0 mg, suggesting its potential applications in smartphones, automotive electronics, and structural health detection.

Flexible ultrathin Nitrogen-Doped carbon mediates the surface charge redistribution of a hierarchical tin disulfide nanoflake electrode for efficient capacitive deionization.

Constructing pseudocapacitive electrodes with high specific capacities is indispensable for increasing the large-scale application of capacitive deionization (CDI). However, the insufficient CDI rate and cycling performance of pseudocapacitive-based electrodes have led to a decline in their use due to the corresponding volumetric expansion and contraction that occurs during long-term CDI processes. Herein, hierarchical porous SnS2 nanoflakes are encapsulated inside an N-doped carbon (NC) matrix to achieve efficient CDI. Benefiting from the synergistic properties of the pseudocapacitive SnS2 nanoflakes and few-layered N-doped carbon, the heterogeneous interface simultaneously provides more available vigorous sites and demonstrates rapid charge-transfer kinetics, resulting in a superior desalination capability (49.86 mg g-1 at 1.2 V), rapid desalination rate (1.66 mg g-1 min-1) and better cyclic stability. Computational research reveals a work function-induced surface charge redistribution of the SnS2@NC heterojunction, which can lead to an auspicious surface electronic structure that reduces the adsorption energy to improve the diffusion kinetics toward sodium adsorption. This work contributes to providing a thoughtful understanding of the interface engineering between transition metal dichalcogenides and NC to construct high-performance CDI electrode materials for further industrialization.

Novel compound heterozygous variants of SLC12A3 gene in a Chinese patient with Gitelman syndrome: a case report.

Background: The Gitelman syndrome (GS) is an autosomal recessive disorder of renal tubular salt handling. Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation, and is caused by variants in the SLC12A3 gene. Gitelman syndrome has a heterogeneous phenotype, which may or may not include a range of clinical signs, posing certain difficulties for clinical diagnosis. Case presentation: A 49-year-old man was admitted to our hospital due to muscular weakness. The patient's history revealed previous recurrent muscular weakness events associated with hypokalemia, featured by a minimum serum potassium value of 2.3 mmol/L. The reported male patient had persistent hypokalemia, hypocalciuria and normal blood pressure, without presenting obvious metabolic alkalosis, growth retardation, hypomagnesemia, hypochloremia or RAAS activation. We performed whole-exome sequencing and identified a novel compound heterozygous variant in the SLC12A3 gene, c.965-1_976delGCGGACATTTTTGinsACCGAAAATTTT in exon8 and c.1112T>C in exon9 in the proband. Conclusion: This is a study to report a heterogeneous phenotype Gitelman syndrome with a novel pathogenic compound heterozygous variant in the SLC12A3 gene. This genetic study expands the variants spectrum, and improve the diagnostic accuracy of Gitelman syndrome. Meanwhile, further functional studies are required to investigate the pathophysiological mechanisms of Gitelman syndrome.