Glycolysis-related lactic acid overproduction creates an "ion-trapping" barrier and immunosuppressive tumor microenvironment that compromise effective intratumoral drug delivery and therapy. Therefore, normalization of tumor microenvironment via lactic acid neutralization can be a promising avenue for overcoming this therapeutic hurdle. In this study, the flexible liposomes loaded with sodium bicarbonate (NaHCO@Flip) were used as a nano-adjuvant to boost chemoimmunotherapy. Their effects on assisting DOXIL and anti-programmed cell death protein 1 (PD-1) therapy were investigated. NaHCO@Flip achieved deep tumor penetration, with the ability to neutralize lactic acid and normalize the acidic tumor microenvironment. NaHCO@Flip is biosafe and can enhance cellular uptake efficiency of doxorubicin (DOX) by overcoming the ion-trapping barrier and amplify immunogenic cell death induced by DOX. The combination therapy of liposomal DOX and NaHCO@Flip demonstrated enhanced inhibition of tumor growth. NaHCO@Flip can also synergize with PD-1 antibody therapy. NaHCO@Flip has the potential to serve as a therapeutic adjuvant for boosting chemoimmunotherapy by overcoming the ion-trapping effect and normalizing the tumor microenvironment.

The regeneration of sweat glands (SwGs) plays a pivotal role in the functional recovery of extensive skin wounds. Recent research has illuminated the possibility of reprogramming human epidermal keratinocytes (HEKs) into induced SwG cells through the ectopic expression of ectodysplasin A. However, the clinical application of this genetic manipulation approach is inherently limited. In this study, we present findings demonstrating that a combination of six compounds can effectively and speedily reprogram HEKs in culture into fully functional SwG cells. These chemically induced SwG-like cells (ciSGCs) closely resemble the morphology, phenotypes, and functional properties of human primary SwG ductal cells. Furthermore, ciSGCs can be stimulated to differentiate into mature SwG cell types in vitro. In a 3D culture system, they can also generate SwG organoids that exhibit structural and biological features akin to native SwGs. Upon transplantation into scalded mouse paw skin, ciSGCs significantly expedited cutaneous wound healing and completely restored the structural and functional aspects of the SwGs. In conclusion, the small molecule cocktail-directed SwG reprogramming offers a non-transgenic and controllable strategy for producing high-quality, clinical-grade SwG cells, showing immense potential for the treatment of burn patients.

Agricultural land use (ALU) critically influences food production and water resource allocation. This study examines the dynamics of ALU in the North China Plain (NCP), a region characterized by intensive agriculture and severe groundwater over-exploitation, focusing on the multidimensional drivers and their implications for water resource management. By employing an elaborate classification scheme based on satellite imagery and extensive first-hand field data, we identified significant shifts in crop patterns. From 2013 to 2017, there was a notable transition from double crops (primarily wheat-maize) to single crops (primarily maize), covering 4600 km and accounting for 42% of single crops in 2013. From 2017 to 2022, there was a shift from single crops to economic forests, encompassing 3600 km and 22% of economic forests in 2017, including orchards, timber trees, and shelter forest belts. These shifts resulted in an 11% decrease in grain acreage (6800 km) but an 11% increase in crop water consumption (6.3 km) during 2013-2022. Notably, water consumption by economic forests increased by 126% (9.4 km) during this period. This study highlights the critical need to balance competing demands for food and water security, providing valuable insights applicable to other agriculturally intensive regions worldwide.

In this study, we successfully synthesized a δ-MnO cathode with O vacancies, encapsulated by C derived from pyromellitic acid, using a facile hydrothermal method followed by annealing in an Ar atmosphere. The cathode's structural stability and charge transfer kinetics are enhanced by inhibiting the formation of the by-product ZnSO(OH)·4HO, regulating the Mn valence state, and suppressing the Jahn-Teller effect through the synergy of C encapsulation and O vacancies. This results in remarkable electrochemical performance, including a large capacity of 421.2 mAh g at 0.1 A g, a high specific energy density of 595.53 Wh kg, and exceptional long-cycle life stability with 90.88% over 4000 cycles at 10 A g, together with superior coulombic efficiency (∼100%) in pure ZnSO electrolyte. Moreover, the cathode materials demonstrate specific antitumor efficacy. In brief, this work introduces an in situ synthetic C encapsulated δ-MnO with O vacancies expected to be applied in both large-scale energy storage and biomedicine.

To investigate the prevalence of gastroesophageal reflux disease (GERD), reflux esophagitis (RE), digestive ulcer gastric ulcer (GU), duodenal ulcer (DU), and Helicobacter pylori infection in Chinese adults aged 18-64 years and their associated factors, a community-based cross-sectional study using a stratified multistage sampling method was conducted. A standardized questionnaire survey, the C-urea breath test, and gastroscopy were performed. Weighted methods were used to estimate the prevalence of diseases or infection mentioned above and their risk factors. Finally, 27,637 participants aged 18-64 years were enrolled from 2017 to 2018. The prevalence (95% confidence interval) of GERD, RE, GU, DU, and H. pylori infection was estimated to be 10.5% (7.8%-14.2%), 5.4% (3.9%-7.3%), 2.5% (1.7%-3.7%), 4.5% (3.6%-5.4%), and 41.5% (36.7%-46.4%), respectively. The fraction of H. pylori infection reached 58.6% and 61.1% among the GU and DU patients, respectively. Weighted multivariable logistic regression models showed that GERD, RE, and GU shared the common risk factors of age and obesity. Dose-response relationships were observed between smoking and all four diseases, as well as alcohol consumption and GERD and H. pylori infection. Northwest China had the highest prevalence of GERD (23.9%), RE (8.7%), GU (7.8%), DU (7.3%), and H. pylori infection (63.6%); however, the southwest region had the highest prevalence of GU but the lowest of DU, RE, and H. pylori infection. Non-steroidal anti-inflammatory drugs were positively associated with GERD risk. On the contrary, a reduced risk of GU was observed among H. pylori-infected patients taking this drug. In summary, the prevalence of GERD, RE, and H. pylori infection still appears high in China. H. pylori infection eradication remains the priority to reduce the burden of peptic ulcer disease. The aging population, high prevalence of overweight or obesity, smoking, and drinking in China could explain the high burden of these diseases, thus suggesting the targeted preventive measures for upper gastrointestinal diseases in the future.

The manipulation of single atom within the metallic kernel of nanoclusters has attracted considerable attention due to its potentials to elucidate kernel-based structure-property relationships at the single-atom level. Herein, new-designed chiral bialkynyl ligands, have been chosen as protective agents to isolate two pairs of 8-electron superatomic silver nanoclusters, R/S-Ag39 and R/S-Ag40. X-ray diffraction analysis reveals that Ag39 and Ag40 with the same number of chiral ligands, possess a closely analogous silver skeleton but a single-atomic difference. The incorporation of an extra Ag atom into Ag40 evokes two significant changes of structure and property compared to Ag39: (i) a reduction in the symmetry of the entire nanocluster, resulting in an enhancement of kernel-related asymmetry g-factor; (ii) a regulation of the transitions (1P → 1D and Ligand → 1D) of excited state, leading to a second near-infrared (NIR-II, 1000-1700 nm) phosphorescent emission red-shift from 1088 to 1150 nm. This work not only provides vital insights into the relationship between structures and ground/excited states chiroptical activities at the single-atom level, but also presents bialkynyl as a promising stabilizing agent for building superatomic metal nanoclusters.

Extensive efforts have been put into reducing the heavy burden of esophageal squamous cell carcinoma (ESCC) in China. However, the joint impact of prevention and treatment on the long-term overall survival (OS) of ESCC patients remains largely unknown. We consecutively recruited 13,255 ESCC patients from two Chinese centers: the Northern center, located in a high-risk area with abundant screening programs; and the Southern center, situated in a non-high-risk area with improved clinical practices. Inter-center comparison, longitudinal intra-center comparison, and a simulation analysis were conducted to investigate the influence of tumor downstaging and high-quality clinical treatment on OS. During a follow-up period of 12.52 years, the Northern center exhibited higher median survival than the Southern center (6.22 vs. 3.15 years; HR = 0.73, 95% CI: 0.69-0.77). Mediation analysis demonstrated that its OS advantage was largely (77.7%) attributed to earlier TNM stage (stage 0-II: 51.3% vs. 24.6%). In temporal analyses, patient survival in the Southern center gradually improved (median survival during 2015-2018 vs. 2009-2014: 3.58 vs. 2.93 years; HR = 0.86, 95% CI: 0.79-0.94), coinciding with the progress of treatment-related indices (completeness of TNM staging in discharge diagnosis [from 53.7% to 99.6%], adoption of minimally invasive esophagectomy [from 0.0% to 51.1%] and right thoracic esophagectomy [from 12.4% to 86.4%], etc.). Simulation analysis further demonstrated that integrating both downstaging and high-quality treatment would lead to the best survival. Tumor downstaging and high-quality clinical treatment have a joint impact on ESCC patient survival. Establishing a comprehensive strategy that integrates cancer prevention with optimal clinical treatment is crucial for alleviating the ESCC burden.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life. Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression. The microbiota-gut-brain axis (MGBA) is closely associated with the occurrence and development of PD and is an effective therapeutic target. Tetrahedral framework nucleic acids (tFNAs) can modulate the microbiome and immune regulation. However, such nucleic acid nanostructures are very sensitive to acids which hinder this promising approach. Therefore, we prepared exosome-like nanovesicles (Exo@tac) from ginger that are acid resistant and equipped with tFNAs modified by antimicrobial peptides (AMP). We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally. Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD. Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.

Managing high-flux waste heat with controllable device working temperature is becoming challenging and critical for the artificial intelligence, communications, electric vehicles, defense and aerospace sectors. Spray cooling, which combines forced convection with phase-change latent heat of working fluids, is promising for high flux heat dissipation. Most of the previous studies on spray cooling enhancement adopted high spray flow rates to strengthen forced convection for high critical heat flux (CHF), leading to a low heat transfer coefficient (HTC). Micro/nanostructured surfaces can enhance boiling, but bubbles inside the structures tend to form a vapor blanket, which can deteriorate heat transfer. This work demonstrates simultaneous enhancement of CHF and HTC in spray cooling by improving both evaporation and liquid film boiling on three-dimensional (3D) ordered hierarchical micro/nano-structured surface. The hierarchical micro/nano-structured surface is designed to coordinate the transport of spray droplets, capillary liquid films, and boiling bubbles to enhance spray cooling performance. Boiling inversion where superheat decreases with increasing heat flux is observed, leading to an ultra-high HTC due to the simultaneous promotion of bubble nucleation and evaporation. Unprecedented CHF is obtained by overcoming the liquid-vapor counterflow, i.e., synergistically facilitating bubble escape and liquid permeation. A record-breaking heat transfer performance of spray cooling is achieved with a maximum heat flux of 1273 W/cm and an HTC of 443.7 kW/(m K) over a 1 cm heating area.

The sequestration of trace hexafluoropropylene (CF) is a critical yet formidable task in the production of high-purity perfluoropropane (CF), an important perfluorinated electronic specialty gas (F-gas) in the advanced electronics industry. Traditional adsorbents struggle with uneven, low-pressure uptake and compromises in selectivity. This work utilizes aperture size-electrostatic potential matching within a robust metal-organic framework (Al-PMA) to facilitate selective, reversible binding of CF while excluding larger CF molecules. The presence of bridging hydroxyl groups (μ-OH) in Al-PMA creates positive electrostatic potential traps that securely anchor CF through strong hydrogen bonding, evidenced by in-situ infrared and F magic angle spinning nuclear magnetic resonance spectroscopy. Breakthrough experiments demonstrate the efficient removal of trace CF from CF under ambient conditions, achieving CF purity exceeding 99.999%. The scalability of Al-PMA synthesis, remarkable stability, and exceptional performance highlight its potential as a promising adsorbent for industrial CF/CF separations.

Tumor metastasis accounts for over 90% of tumor-related deaths, prompting the development of fluorescently labeled tumor-specific molecular imaging agents for differentiating tumors from normal tissues. However, early detection of metastasis lesions by tracking tumor markers alone has proven to be challenging. Herein, we reported a glycopeptide-based bispecific fluorescence probe (bsProbe) for earlier detection of bladder cancer and metastasis. By simultaneously recognition (tumor & tumor microenvironment) and in vivo self-assembly, the tumor accumulation of bsProbe (12.3% ID/g) was obviously increased by ∼6 fold compared with that in CXCR4 specific fluorescence probe (sProbe), indicating the obvious advantages of bsProbe over existing tumor metastasis detection probes. Additionally, bsProbe substantially broadens the tumor diagnosis window and enhances the detection signal to noise ratio (SNR: approximately 9.5), permitting early diagnosis of lung micro-metastasis (∼1 mm), precise identifying of tumor boundaries and micro-tumors in orthotopic tumor models. More importantly, bsProbe was demonstrated to distinguish malignant from benign specimen with a specificity of 90.48% and sensitivity of 92.22% in 195 clinical specimens of bladder cancer patients. Taken together, this novel synergetic targeting (CD206 × CXCR4) strategy provides an attractive method for earlier detection of bladder cancer and metastasis, which might be further extended to the imaging-guided surgery of clinical invisible tumors.