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Gamma-Aminobutyric acid (GABA) is a derivative of L-glutamate, also a precursor for the synthesis of 2-pyrrolidone, which is a monomer of nylon-4. This study achieved a one-step biosynthesis of GABA and 2-pyrrolidone by Halomonas bluephagenesis overexpressing key genes involved in GABA and 2-pyrrolidone synthesis and deleting GABA degradation genes combined with reducing the degradation of 2-pyrrolidone precursor. The resulting H. bluephagenesis strain WLp07 was employed in whole-cell catalysis, producing 357 g/L of GABA and 72 wt% of PHA. Furthermore, a self-flocculating H. bluephagenesis allowed rapid, convenient recycling of the cells, achieving 880 g/L of GABA over three cycles. Shake flask studies showed that engineered H. bluephagenesis harboring ß-alanine CoA transferase was able to synthesized 2-pyrrolidone from GABA. H. bluephagenesis as a chassis of next generation industrial biotechnology (NGIB), demonstrated its diverse ability to produce GABA and 2-pyrrolidone in addition to intracellular PHA.

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The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation. Additionally, it raises citrate levels in the tricarboxylic acid (TCA) cycle, facilitating the synthesis of citrate-containing apatite during hBMSCs osteogenesis. Furthermore, 3HB administration significantly increased bone mass in rats with osteoporosis induced by ovariectomy. The findings also showed that P(3HB-co-4HB) scaffold substantially enhances long-term vascularized bone regeneration in rat cranial defect models. These findings reveal a previously unknown role of 3HB in promoting osteogenesis of hBMSCs and highlight the metabolic activation of P(3HB-co-4HB) scaffold for bone regeneration.

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BACKGROUND: Currently, tumor budding (TB) is defined as an important factor for a poor prognosis in various types of cancers. The authors identified a significant presence of TB-like structures at the tumor invasive front in giant cell tumor of bone (GCTB), which may have the same biologic function as TB. The objective of this report was to describe the distribution of TB in GCTB and investigate its correlation with clinicopathologic characteristics, the immune microenvironment, survival prognosis, and response to denosumab treatment. METHODS: This multicenter cohort study included 426 patients with GCTB who received treatment between 2012 and 2021 at four centers. Two independent pathologists performed visual assessments of TBL structures in hematoxylin-and-eosin-stained tumor sections. Immunohistochemistry was used to evaluate tumor-infiltrating lymphocyte subtypes (CD3-positive, CD4-positive, CD8-positive, CD20-positive, programmed cell death protein-1-positive, programmed cell death-ligand 1positive, and FoxP3-positive) as well as Ki-67 expression levels in 426 tissue samples. These parameters were then analyzed for associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]), clinicopathologic characteristics, and response to denosumab treatment. RESULTS: High-grade TB was associated with poorer LRFS and OS in both patient groups. In addition, TB was correlated with various clinicopathologic features, tumor-infiltrating lymphocyte expression, and response to denosumab treatment. TB outperformed the traditional Enneking and Campanacci staging systems in predicting patient LRFS and OS. CONCLUSIONS: The current data support the assessment of TBL structures as a reliable prognostic tool in GCTB, potentially aiding in the development of personalized treatment strategies for patients.

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We conducted in a common garden experiment to explore the differences in soil enzyme activity, stoichiometry, and their influencing factors among a secondary Castanopsis carlesii forest, 10-year-old C. carlesii plantation, and Cunninghamia lanceolata plantation. The results showed that compared to the secondary forest, the soil organic carbon, total nitrogen, and dissolved organic carbon significantly decreased by 42.6%, 47.4%, and 60.9% in C. carlesii plantation, and by 42.9%, 36.7%, and 61.1% in C. lanceolata plantation. Soil microbial biomass C, microbial biomass N (MBN), and microbial biomass phosphorus decreased significantly by 40.6%, 35.5%, and 45.9% in C. carlesii plantation, and by 53.7%、56.4%, and 61.7% in C. lanceolata plantation. Compared to the secondary forest, soil enzymes activities in C. carlesii plantation did not change significantly, but in C. lanceolata plantation, the activities of ß-1,4-glucosidase and cellobiohydrolase significantly decreased by 51.2% and 59.8%, ß-N-acetyl glucosaminidase and acid phosphatase decreased significantly by 41.0% and 29.8%, and enzymatic C:N acquisition ratio and enzymatic C:P acquisition ratio significantly decreased by 11.3% and 7.7%, respectively. Results of redundancy analysis indicated that MBN and NO3--N were the primary factors influencing soil enzyme activity and enzymic stoichiometry. Collectively, there were significant differences in soil enzyme activity and microbial nutrient demands among different forest stands. Compared to secondary forests, the establishment of C. lanceolata plantations would intensify nutrient competition between plants and microbes, and exacerbate the N and P limitations for microbes.

Asunto(s)

Carbono , Cunninghamia , Bosques , Nitrógeno , Microbiología del Suelo , Suelo , Suelo/química , Nitrógeno/análisis , Nitrógeno/metabolismo , China , Cunninghamia/crecimiento & desarrollo , Carbono/análisis , Fósforo/análisis , Fósforo/metabolismo , Clima Tropical , Fagaceae/crecimiento & desarrollo , Árboles/crecimiento & desarrollo , Ecosistema

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The corticostriatal connection plays a crucial role in cognitive, emotional, and motor control. However, the specific roles and synaptic transmissions of corticostriatal connection are less studied, especially the corticostriatal transmission from the anterior cingulate cortex (ACC). Here, a direct glutamatergic excitatory synaptic transmission in the corticostriatal projection from the ACC is found. Kainate receptors (KAR)-mediated synaptic transmission is increased in this corticostriatal connection both in vitro and in vivo seizure-like activities. GluK1 containing KARs and downstream calcium-stimulated adenylyl cyclase subtype 1 (AC1) are involved in the upregulation of KARs following seizure-like activities. Inhibiting the activities of ACC or its corticostriatal connection significantly attenuated pentylenetetrazole (PTZ)-induced seizure. Additionally, injection of GluK1 receptor antagonist UBP310 or the AC1 inhibitor NB001 both show antiepileptic effects. The studies provide direct evidence that KARs are involved in seizure activity in the corticostriatal connection and the KAR-AC1 signaling pathway is a potential novel antiepileptic strategy.

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Tunable ultrasonic focusing holds great significance in both medicine and engineering. Recent advancements in metalenses have introduced approaches for tunable acoustic focusing, but their complex configurations and limited tuning range remain challenges. Here, acoustic Moiré metalenses (AMMs) are proposed to achieve continuously tunable ultrasonic focusing in water. Two cascading metasurfaces that can function as Moiré diffractive elements make up the AMM. By mutually rotating the metasurface, the focal point of the AMM can be continuously tuned in a large range. The focal length can be adjusted continuously from ∼14.3λ0to ∼50λ0for the axial focusing. We further show that the well-designed AMM can achieve the continuously tunable lateral focusing, with the deflection angle of the focal point being tunable between approximately -40°,40°. Both simulation and experimental results confirm the excellent tunable focusing performances of the AMMs. The proposed AMMs with continuously tunable focusing capability may have potential applications in ultrasonic imaging and ultrasound treatment.

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Primary dysmenorrhea (PD) is a common global health concern. However, limited studies explored the association between soft drinks intake and PD among female undergraduates in China. To determine the association between soft drinks (carbonated soft drinks, etc.) as well coffee intake and the incidence/severity of PD among female undergraduates in China. We performed a cross-sectional study among 1809 female undergraduates in China from September 29, 2020 to October 22, 2020. The demographic information and menstrual information of the participants were collected by a self-administrated questionnaire. Chi-square test, ANOVA test, and logistic regression test were used to investigate the association between soft drinks intake and the incidence/severity of PD. We also conducted stratification analysis among different locations (rural or urban). The prevalence of PD was 47.1% (n = 852). There were 221 (25.9%) participants suffered from severe pain. In the participants with PD, the OR of carbonated soft drinks intake was 1.244 (95% CI 1.010-1.533). Among the participants with PD from rural areas, the OR of carbonated soft drinks intake was 1.402 (95% CI 1.045-1.881), compared with the non-carbonated soft drink group. In the participants with moderate and severe PD, the OR of coffee intake was 0.451 (95% CI 0.228-0.892), compared with the non-coffee-drinking group. There was a significant association between carbonated soft drinks intake frequency and the severity of PD (P < 0.05). Our study showed that carbonated soft drinks intake is a risk factor for PD, especially in participants from rural areas. Coffee intake is a protective factor for the severity of PD. Periodical awareness programs about adverse effects of excessive soft drink consumption should be introduced to reduce the prevalence and exacerbation of PD. Coffee intake might be helpful to relieve the severity of PD.

Asunto(s)

Bebidas Gaseosas , Dismenorrea , Estudiantes , Humanos , Femenino , Dismenorrea/epidemiología , Dismenorrea/etiología , China/epidemiología , Estudiantes/estadística & datos numéricos , Bebidas Gaseosas/efectos adversos , Adulto Joven , Estudios Transversales , Café/efectos adversos , Prevalencia , Adulto , Adolescente , Encuestas y Cuestionarios , Universidades , Factores de Riesgo , Pueblos del Este de Asia

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The prognosis of septic patients with cirrhosis is worse compared to septic patients without cirrhosis. Early and accurate prognosis determination in patients with cirrhosis and sepsis is pivotal for guiding treatment decisions. The aim of this study was to investigate the association between albumin-corrected anion gap (ACAG) and clinical prognosis of patients with sepsis and cirrhosis. This study extracted data of patients with sepsis and cirrhosis from the Medical Information Mart for Intensive Care (MIMIC-IV) database. A total of 1340 patients (64.6% male) were enrolled. After confounders adjusting, elevated ACAG had a significant association with 28-day mortality (HR1.604; 95% CI 1.258-2.048; P < 0.001). Restricted cubic spline revealed that a linear relationship between ACAG and 28-day mortality (P-nonlinear = 0.089, P-overall = 0.001). According to the ROC curve analysis, the ACAG demonstrated a higher area under the curve (AUC) of 0.703 compared to AG (0.675). Kaplan-Meier analysis revealed higher 28-day mortality in high ACAG group (log-rank test, χ^2 = 175.638, P < 0.001). Furthermore, subgroup analysis showed a significant interaction between ACAG and etiology of cirrhosis (P for interaction = 0.014). Therefore, ACAG could provide clinicians with valuable insights for guiding interventions in this high-risk population.

Asunto(s)

Cirrosis Hepática , Sepsis , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/complicaciones , Masculino , Femenino , Sepsis/mortalidad , Sepsis/complicaciones , Pronóstico , Persona de Mediana Edad , Anciano , Equilibrio Ácido-Base , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Curva ROC , Estimación de Kaplan-Meier , Biomarcadores

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To address the problems of low accuracy in fault diagnosis of oil-immersed transformers, poor state perception ability and real-time collaboration during diagnosis feedback, a fault diagnosis method for transformers based on the integration of digital twins is proposed. Firstly, fault sample balance is achieved through Iterative Nearest Neighbor Oversampling (INNOS), Secondly, nine-dimensional ratio features are extracted, and the correlation between dissolved gases in oil and fault types is established. Then, sparse principal component analysis (SPCA) is used for feature fusion and dimensionality reduction. Finally, the Aquila Optimizer (AO) is introduced to optimize the parameters of the Kernel Extreme Learning Machine (KELM), establishing the optimal AO-KELM diagnosis model. The final fault diagnosis accuracy reaches 98.1013%. Combining transformer digital twin models, real-time interaction mapping between physical entities and virtual space is achieved, enabling online diagnosis of transformer faults. Experimental results show that the method proposed in this paper has high diagnostic accuracy and strong stability, providing reference for the intelligent operation and maintenance of transformers.

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Sucrose is a commonly utilized nutritive sweetener in food and beverages due to its abundance in nature and low production costs. However, excessive intake of sucrose increases the risk of metabolic disorders, including diabetes and obesity. Therefore, there is a growing demand for the development of nonnutritive sweeteners with almost no calories. d-Allulose is an ultra-low-calorie, rare six-carbon monosaccharide with high sweetness, making it an ideal alternative to sucrose. In this study, we developed a cell factory for d-allulose production from sucrose using Escherichia coli JM109 (DE3) as a chassis host. The genes cscA, cscB, cscK, alsE, and a6PP were co-expressed for the construction of the synthesis pathway. Then, the introduction of ptsG-F and knockout of ptsG, fruA, ptsI, and ptsH to reprogram sugar transport pathways resulted in an improvement in substrate utilization. Next, the carbon fluxes of the Embden-Meyerhof-Parnas and the pentose phosphate pathways were regulated by the inactivation of pfkA and zwf, achieving an increase in d-allulose titer and yield of 154.2% and 161.1%, respectively. Finally, scaled-up fermentation was performed in a 5 L fermenter. The titer of d-allulose reached 11.15 g/L, with a yield of 0.208 g/g on sucrose.

RESUMEN

INTRODUCTION: The purpose of this research was to determine how the P53/microRNA-34a (miR-34a)/survivin pathway contributes to oxaliplatin-induced (L-OHP) cell inhibition in gastric cancer. METHODS: The BGC-823 gastric cancer cells were selected, and we examined their viability following treatment with L-OHP at different concentrations and time periods. The expression levels of miR-34a, P53, and survivin in the cells were determined. RESULTS: In the 12- and 24-h groups, drug concentration of 15 µg/cm² (p < .005 in both) significantly lowered cell viability. In comparison to the control group, miR-34a mRNA expression, P53 mRNA expression, and protein expression were all significantly greater in the 24-h group (p = .0324, p = .0069, p = .0260, respectively), but survivin mRNA and protein expressions were significantly lower than those in the control group (p = .0338, p = .0032, respectively). There was a significant decrease in gastric cancer cells in the miR-34a overexpression group (p = .0020), a significant increase in P53 mRNA and protein expression compared to the control group (p = .0080, p = .0121, respectively), and a significant decrease in survivin mRNA and protein expression compared to the control group. (p = .0213, p = .0069, respectively). CONCLUSION: Oxaliplatin inhibits tumor growth, invasion, and metastasis by upregulating miR-34a, activating the expression of the upstream P53 gene, and driving the downregulation of survivin (P53/miR-34a/survivin axis) in BGC-823 gastric cancer cells.

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Proteínas Inhibidoras de la Apoptosis , MicroARNs , Oxaliplatino , Neoplasias Gástricas , Survivin , Proteína p53 Supresora de Tumor , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , MicroARNs/genética , Humanos , Oxaliplatino/farmacología , Survivin/metabolismo , Survivin/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Antineoplásicos/farmacología , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad

RESUMEN

D-Glucose-to-L-sorbose isomerization on Lewis acidic zeolite is a highly attractive avenue for sorbose production. But the L-sorbose yield is limited by the competing D-glucose-to-D-fructose isomerization and reaction equilibrium. In this work, it is suggested that ethanol directs the glucose conformation for selective D-glucose-to-L-sorbose isomerization. It also reacts with the produced L-sorbose to form ethyl-sorboside, which allows the D-glucose-to-L-sorbose isomerization to proceed beyond the thermodynamic equilibrium limit.  It is shown that a bifunctional zeolite Beta containing framework titanium (Ti) and boron (B) is a selective catalyst for this tandem reaction: Lewis acidic framework Ti catalyzes the D-glucose-to-L-sorbose isomerization via an intramolecular 5,1-hydride shift process as confirmed by isotopic tracing experiments followed by 13C-NMR, while weak Brønsted acid framework B selectively promotes the sorbose ketalization with ethanol. A remarkably high yield of L-sorbose with a high fraction of sugar (>95%: 27% unreacted glucose, 11.4% fructose, 57% sorbose) was obtained after the mixture produced in ethanol was hydrolyzed.

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Renal unilateral ischemia-reperfusion injury (UIRI) constitutes a significant global health challenge, with poor recovery leading to chronic kidney disease and subsequent renal fibrosis. Extracellular vesicles (EVs) present substantial potential benefits for renal diseases. However, the limited yield and efficacy of EVs produced through traditional methodologies (2D-EVs) severely restrict their widespread application. Moreover, the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored. In this study, we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology (3D-EVs) with a tail vein injection method, introducing a novel treatment strategy for UIRI. Our comparison of the biological functions of 2D-EVs and 3D-EVs, both in vitro and in vivo, reveals that 3D-EVs significantly outperform 2D-EVs. Specifically, in vitro, 3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation (H/R)-induced injuries by reducing epithelial-mesenchymal transformation, extracellular matrix deposition, and ferroptosis. In vivo, 3D-EVs exhibit enhanced therapeutic effects, as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys. We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells (TECs) ferroptosis through the modulation of SLC7A11 and GPX4 expression. Our findings suggest that bioprinted mesenchymal stem cells microfiber-derived EVs significantly ameliorate renal UIRI, opening new avenues for effective and efficient EV-based therapies in UIRI treatment.

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There is extensive geologic evidence of ancient volcanic activity on the Moon, but it is unclear how long that volcanism persisted. Magma fountains produce volcanic glasses, which have previously been found in samples of the Moon's surface. We investigated ~3000 glass beads in lunar soil samples collected by the Chang'e-5 mission and identified three as having a volcanic origin on the basis of their textures, chemical compositions, and sulfur isotopes. Uranium-lead dating of the three volcanic glass beads shows that they formed 123 ± 15 million years ago. We measured high abundances of rare earth elements and thorium in these volcanic glass beads, which could indicate that such recent volcanism was related to local enrichment of heat-generating elements in the mantle sources of the magma.

Asunto(s)

Lipopolisacáridos , Lonicera , Sistema de Señalización de MAP Quinasas , Factor de Necrosis Tumoral alfa , Humanos , Células HT29 , Lonicera/química , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Extractos Vegetales/farmacología , Extractos Vegetales/química , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética

RESUMEN

With the increasing demand for Li, the recovery of Li from solid waste, such as Li-containing Al electrolytes, is receiving growing attention. However, Li-containing Al electrolytes often contain large amounts of F, leading to environmental pollution. Herein, a new method for preparing water-soluble Li salt from waste Li-containing Al electrolytes with high F and Na contents is proposed based on CaO roasting and water leaching. The effects of different roasting and leaching conditions on the Li leaching efficiency and reaction pathway were systematically investigated. Under the optimum processing conditions, the Li leaching efficiency reached 98%, while those of Na and F were 98.41% and 0.24%, respectively. Phase evolution analysis showed that the addition of CaO promoted the conversion of LiF and Na2LiAlF6 to Li2O, whereas F entered the slag phase as CaF2, which could be reused as a raw material for steel refinement. Overall, this study proposes an efficient and environmentally friendly method for the treatment and resource utilization of waste Al electrolytes with high F and Na contents.

Asunto(s)

Electrólitos , Litio , Litio/química , Aluminio/química , Agua/química , Sodio/química , Sodio/análisis , Residuos Sólidos/análisis

RESUMEN

Background: Diffuse alveolar hemorrhage (DAH) is a catastrophic clinical syndrome and one of the manifestations of pulmonary involvement in systemic lupus erythematosus (SLE), which is characterized by hemoptysis, diffuse pulmonary infiltrates, and respiratory failure. However, the treatment options for DAH remain limited, and DAH-related studies are needed to explore more effective therapeutic directions for better disease management and improved prognosis. Methods: This study utilized the pristane-induced DAH murine model to mimic the pathological process of DAH in patients with SLE. Proteomic analysis was conducted to detect differentially expressed proteins (DEPs) in the plasma of surviving and non-surviving mice, followed by an analysis of biological functions and pathways. The most significant DEP was then confirmed in the plasma of SLE patients with or without DAH and DAH murine model with or without fatal outcomes. Finally, the therapeutic value of haptoglobin (Hp) replacement was validated in a DAH murine model through lung histopathology, RT-qPCR, and survival analysis. Results: This study identified 178 DEPs, with 118 upregulated and 60 downregulated DEPs in the non-survival group. Within a set of notable Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, complement and coagulation cascades emerged as the most prominent pathway associated with the process of DAH. Later, the most significant DEP, haptoglobin (Hp), was confirmed to exhibit a significant decrease in the plasma of individuals with SLE-DAH and DAH murine model with poor outcomes by the ELISA test. Finally, compared with the control group, the severity of DAH in the Hp treatment group was alleviated significantly, as manifested by the decreased levels of pro-inflammatory cytokines (IL-6 and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-ß), and decreased mortality. Conclusion: A reduction in plasma Hp levels was observed in SLE-DAH, and the replacement therapy with Hp could alleviate pulmonary hemorrhage and reduce mortality in DAH mice. This study identified Hp as a potential biomarker for its clinical diagnosis and a direction for treatment.

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The rising humid heat is regarded as a severe threat to human survivability, but the proper integration of humid heat into heat-health alerts is still being explored. Using state-of-the-art epidemiological and climatological datasets, we examined the association between multiple heat stress indicators (HSIs) and daily human mortality in 739 cities worldwide. Notable differences were observed in the long-term trends and timing of heat events detected by HSIs. Air temperature (Tair) predicts heat-related mortality well in cities with a robust negative Tair-relative humidity correlation (CT-RH). However, in cities with near-zero or weak positive CT-RH, HSIs considering humidity provide enhanced predictive power compared to Tair. Furthermore, the magnitude and timing of heat-related mortality measured by HSIs could differ largely from those associated with Tair in many cities. Our findings provide important insights into specific regions where humans are vulnerable to humid heat and can facilitate the further enhancement of heat-health alert systems.

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Traditionally, the acquisition of 2D materials involved the exfoliation of layered crystals. However, the anisotropic bonding arrangements within 3D crystals indicate they are mechanically reminiscent of 2D counterparts and could also be exfoliated into nanosheets. This report delineates the preparation of 2D nanosheets from six representative 3D metal-organic frameworks (MOFs) through liquid-phase exfoliation. Notably, the cleavage planes of exfoliated nanosheets align perpendicular to the direction of the minimum elastic modulus (Emin) within the pristine 3D frameworks. The findings suggest that the in-plane and out-of-plane bonding forces of the exfoliated nanosheets can be correlated with the maximum elastic modulus (Emax) and Emin of the 3D frameworks, respectively. Emax influences the ease of cleaving adjacent layers, while Emin governs the ability to resist cracking of layers. Hence, a combination of large Emax and small Emin indicates an efficient exfoliation process, and vice versa. The ratio of Emax/Emin, denoted as Amax/min, is adopted as a universal index to quantify the ease of mechanical exfoliation for 3D MOFs. This ratio, readily accessible through mechanical experiments and computation, serves as a valuable metric for selecting appropriate exfoliation methods to produce surfactant-free 2D nanosheets from various 3D materials.