The quantity, function and anti-tumor effect of Mucosal associated invariant T cells in patients with bladder cancer.

BACKGROUND: Bladder cancer (BC), a prevalent malignancy in the urinary system, often poses challenges for effective treatment. Immunotherapy, harnessing the immune system, has exhibited promise in early-stage clinical trials. Mucosal associated invariant T (MAIT) cells, a subset of immune cells implicated in various diseases, including certain cancer, have yet to be explored in BC patients. We aimed to investigate the quantity, function, and anti-tumor effects of MAIT cells in BC patients. METHODS: A total of 75 newly diagnosed BC patients and 183 healthy volunteers were included. Blood samples were collected and analyzed to evaluate the quantity and function of MAIT cells. Surgical resection provided BC tissues for further analysis, and the clinical features of BC tumors were collected and their relationship with MAIT cells was explored. RESULTS: MAIT cells were identified in both healthy individuals and BC patients. The proportion of MAIT cells in the peripheral blood of BC patients did not significantly differ from that of healthy controls. However, the study revealed a correlation between the proportion of IFN-γ producing MAIT cells and tumor number and invasion in BC patients. Furthermore, MAIT cells exhibited cytotoxic effects on BC cells in vitro and in vivo. CONCLUSIONS: This study sheds light on the role of MAIT cells in BC. While the quantity of MAIT cells showed no significant change in BC patients, their functional attributes and association with tumor characteristics suggest their potential as an immunotherapy target in BC treatment.

Gradient Interphase Engineering Enabled by Anionic Redox for High-Voltage and Long-Life Li-Ion Batteries.

Intelligent utilization of the anionic redox reaction (ARR) in Li-rich cathodes is an advanced strategy for the practical implementation of next-generation high-energy-density rechargeable batteries. However, due to the intrinsic complexity of ARR (e.g., nucleophilic attacks), the instability of the cathode-electrolyte interphase (CEI) on a Li-rich cathode presents more challenges than typical high-voltage cathodes. Here, we manipulate CEI interfacial engineering by introducing an all-fluorinated electrolyte and exploiting its interaction with the nucleophilic attack to construct a gradient CEI containing a pair of fluorinated layers on a Li-rich cathode, delivering enhanced interfacial stability. Negative/detrimental nucleophilic electrolyte decomposition has been efficiently evolved to further reinforce CEI fabrication, resulting in the construction of LiF-based indurated outer shield and fluorinated polymer-based flexible inner sheaths. Gradient interphase engineering dramatically improved the capacity retention of the Li-rich cathode from 43 to 71% after 800 cycles and achieved superior cycling stability in anode-free and pouch-type full cells (98.8% capacity retention, 220 cycles), respectively.

Implanting Transition Metal into Li2 O-Based Cathode Prelithiation Agent for High-Energy-Density and Long-Life Li-Ion Batteries.

Compensating the irreversible loss of limited active lithium (Li) is essentially important for improving the energy-density and cycle-life of practical Li-ion battery full-cell, especially after employing high-capacity but low initial coulombic efficiency anode candidates. Introducing prelithiation agent can provide additional Li source for such compensation. Herein, we precisely implant trace Co (extracted from transition metal oxide) into the Li site of Li2 O, obtaining (Li0.66 Co0.11 □0.23 )2 O (CLO) cathode prelithiation agent. The synergistic formation of Li vacancies and Co-derived catalysis efficiently enhance the inherent conductivity and weaken the Li-O interaction of Li2 O, which facilitates its anionic oxidation to peroxo/superoxo species and gaseous O2 , achieving 1642.7 mAh/g~Li2O prelithiation capacity (≈980 mAh/g for prelithiation agent). Coupled 6.5 wt % CLO-based prelithiation agent with LiCoO2 cathode, substantial additional Li source stored within CLO is efficiently released to compensate the Li consumption on the SiO/C anode, achieving 270 Wh/kg pouch-type full-cell with 92 % capacity retention after 1000 cycles.

One-Step Surface-to-Bulk Modification of High-Voltage and Long-Life LiCoO2 Cathode with Concentration Gradient Architecture.

Raising the charging cut-off voltage of layered oxide cathodes can improve their energy density. However, it inevitably introduces instabilities regarding both bulk structure and surface/interface. Herein, exploiting the unique characteristics of high-valence Nb5+ element, a synchronous surface-to-bulk-modified LiCoO2 featuring Li3 NbO4 surface coating layer, Nb-doped bulk, and the desired concentration gradient architecture through one-step calcination is achieved. Such a multifunctional structure facilitates the construction of high-quality cathode/electrolyte interface, enhances Li+ diffusion, and restrains lattice-O loss, Co migration, and associated layer-to-spinel phase distortion. Therefore, a stable operation of Nb-modified LiCoO2 half-cell is achieved at 4.6 V (90.9% capacity retention after 200 cycles). Long-life 250 Wh kg-1 and 4.7 V-class 550 Wh kg-1 pouch cells assembled with graphite and thin Li anodes are harvested (both beyond 87% after 1600 and 200 cycles). This multifunctional one-step modification strategy establishes a technological paradigm to pave the way for high-energy density and long-life lithium-ion cathode materials.

Clinical case analysis of 32 children aged 0-6 years with lead poisoning in Nanning, China.

Lead is one of the heavy metals that is toxic and widely distributed in the environment, and children are more sensitive to the toxic effects of lead because the blood-brain barrier and immune system are not yet well developed. The objective of the study was to investigate the clinical characteristics of lead poisoning in children aged 0∼6 years in a hospital in Guangxi, and to provide scientific basis for the prevention and treatment of lead poisoning. We collected and analyzed the clinical data of 32 children with lead poisoning admitted to a hospital in Guangxi from 2010 to 2018. The results showed that most of the 32 cases presented with hyperactivity, irritability, poor appetite, abdominal pain, diarrhea, or constipation. The hemoglobin (HGB), mean corpusular volume (MCV), mean corpuscular hemoglobin (MCH), and hematocrit (HCT) of the lead-poisoned children were all decreased to different degrees and were below normal acceptable levels. Urinary ß2-microglobulin was increased. Blood lead levels (BLL) decreased significantly after intravenous injection of the lead chelator, calcium disodium edetate (CaNa2-EDTA). In addition, HGB returned to normal levels, while MCV, MCH, and HCT increased but remained below normal levels. Urinary ß2-microglobulin was reduced to normal levels. Therefore, in this cohort of children, the high-risk factors for lead poisoning are mainly Chinese medicines, such as baby powder. In conclusion, lead poisoning caused neurological damage and behavioral changes in children and decreased erythrocyte parameters, leading to digestive symptoms and renal impairment, which can be attenuated by CaNa2-EDTA treatment.

Manipulated Fluoro-Ether Derived Nucleophilic Decomposition Products for Mitigating Polarization-Induced Capacity Loss in Li-Rich Layered Cathode.

Electrolyte engineering is a fascinating choice to improve the performance of Li-rich layered oxide cathodes (LRLO) for high-energy lithium-ion batteries. However, many existing electrolyte designs and adjustment principles tend to overlook the unique challenges posed by LRLO, particularly the nucleophilic attack. Here, we introduce an electrolyte modification by locally replacing carbonate solvents in traditional electrolytes with a fluoro-ether. By benefit of the decomposition of fluoro-ether under nucleophilic O-related attacks, which delivers an excellent passivation layer with LiF and polymers, possessing rigidity and flexibility on the LRLO surface. More importantly, the fluoro-ether acts as "sutures", ensuring the integrity and stability of both interfacial and bulk structures, which contributed to suppressing severe polarization and enhancing the cycling capacity retention from 39 % to 78 % after 300 cycles for the 4.8 V-class LRLO. This key electrolyte strategy with comprehensive analysis, provides new insights into addressing nucleophilic challenge for high-energy anionic redox related cathode systems.

Lattice Engineering on Li2CO3-Based Sacrificial Cathode Prelithiation Agent for Improving the Energy Density of Li-Ion Battery Full-Cell.

Developing sacrificial cathode prelithiation technology to compensate for active lithium loss is vital for improving the energy density of lithium-ion battery full-cells. Li2CO3 owns high theoretical specific capacity, superior air stability, but poor conductivity as an insulator, acting as a promising but challenging prelithiation agent candidate. Herein, extracting a trace amount of Co from LiCoO2 (LCO), a lattice engineering is developed through substituting Li sites with Co and inducing Li defects to obtain a composite structure consisting of (Li0.906Co0.043▫0.051)2CO2.934 and ball milled LiCoO2 (Co-Li2CO3@LCO). Notably, both the bandgap and Li─O bond strength have essentially declined in this structure. Benefiting from the synergistic effect of Li defects and bulk phase catalytic regulation of Co, the potential of Li2CO3 deep decomposition significantly decreases from typical >4.7 to ≈4.25 V versus Li/Li+, presenting >600 mAh g-1 compensation capacity. Impressively, coupling 5 wt% Co-Li2CO3@LCO within NCM-811 cathode, 235 Wh kg-1 pouch-type full-cell is achieved, performing 88% capacity retention after 1000 cycles.

From Li to Na: Exploratory Analysis of Fe-Based Phosphates Polyanion-Type Cathode Materials by Mn Substitution.

Both LiFePO4 (LFP) and NaFePO4 (NFP) are phosphate polyanion-type cathode materials, which have received much attention due to their low cost and high theoretical capacity. Substitution of manganese (Mn) elements for LFP/NFP materials can improve the electrochemical properties, but the connection between local structural changes and electrochemical behaviors after Mn substitution is still not clear. This study not only achieves improvements in energy density of LFP and cyclic stability of NFP through Mn substitution, but also provides an in-depth analysis of the structural evolutions induced by the substitution. Among them, the substitution of Mn enables LiFe0.5 Mn0.5 PO4 to achieve a high energy density of 535.3 Wh kg-1 , while NaFe0.7 Mn0.3 PO4 exhibits outstanding cyclability with 89.6% capacity retention after 250 cycles. Specifically, Mn substitution broadens the ion-transport channels, improving the ion diffusion coefficient. Moreover, LiFe0.5 Mn0.5 PO4 maintains a more stable single-phase transition during the charge/discharge process. The transition of NaFe0.7 Mn0.3 PO4 to the amorphous phase is avoided, which can maintain structural stability and achieve better electrochemical performance. With systematic analysis, this research provides valuable guidance for the subsequent design of high-performance polyanion-type cathodes.

Full-Dimensional Analysis of Electrolyte Decomposition on Cathode-Electrolyte Interface: Establishing Characterization Paradigm on LiNi0.6Co0.2Mn0.2O2 Cathode with Potential Dependence.

Cathode electrolyte interphase (CEI) layers derived from electrolyte oxidative decomposition can passivate the cathode surface and prevent its direct contact with electrolyte. The inorganics-dominated inner solid electrolyte layer (SEL) and organics-rich outer quasi-solid-electrolyte layer (qSEL) constitute the CEI layer, and both merge at the junction without a clear boundary, which assures the CEI layer with both ionic-conducting and electron-blocking properties. However, the typical "wash-then-test" pattern of characterizations aiming at the microstructure of CEI layers would dissolve the qSEL and even destroy the SEL, leading to an overanalysis of electrolyte decomposition pathway and misassignment of CEI architecture (e.g., component and morphology). In this study, we established a full-dimensional characterization paradigm (combining Fourier transform infrared, solution NMR, X-ray photoelectron spectroscopy, and mass spectrometry technologies) and reconstructed the original CEI layer model. Besides, the feasibility of this characterization paradigm has been verified in a wide operating voltage range on a typical LiNixMnyCozO2 cathode.

Role of Substitution Elements in Enhancing the Structural Stability of Li-Rich Layered Cathodes.

Element doping/substitution has been recognized as an effective strategy to enhance the structural stability of layered cathodes. However, abundant substitution studies not only lack a clear identification of the substitution sites in the material lattice, but the rigid interpretation of the transition metal (TM)-O covalent theory is also not sufficiently convincing, resulting in the doping/substitution proposals being dragged into design blindness. In this work, taking Li1.2Ni0.2Mn0.6O2 as a prototype, the intense correlation between the "disordered degree" (Li/Ni mixing) and interface-structure stability (e.g., TM-O environment, slab/lattice, and Li+ reversibility) is revealed. Specifically, the degree of disorder induced by the Mg/Ti substitution extends in the opposite direction, conducive to sharp differences in the stability of TM-O, Li+ diffusion, and anion redox reversibility, delivering fairly distinct electrochemical performance. Based on the established paradigm of systematic characterization/analysis, the "degree of disorder" has been shown to be a powerful indicator of material modification by element substitution/doping.

Prolonged lifespan of initial-anode-free lithium-metal battery by pre-lithiation in Li-rich Li2Ni0.5Mn1.5O4 spinel cathode.

Anode-free lithium metal batteries (AF-LMBs) can deliver the maximum energy density. However, achieving AF-LMBs with a long lifespan remains challenging because of the poor reversibility of Li+ plating/stripping on the anode. Here, coupled with a fluorine-containing electrolyte, we introduce a cathode pre-lithiation strategy to extend the lifespan of AF-LMBs. The AF-LMB is constructed with Li-rich Li2Ni0.5Mn1.5O4 cathodes as a Li-ion extender; the Li2Ni0.5Mn1.5O4 can deliver a large amount of Li+ in the initial charging process to offset the continuous Li+ consumption, which benefits the cycling performance without sacrificing energy density. Moreover, the cathode pre-lithiation design has been practically and precisely regulated using engineering methods (Li-metal contact and pre-lithiation Li-biphenyl immersion). Benefiting from the highly reversible Li metal on the Cu anode and Li2Ni0.5Mn1.5O4 cathode, the further fabricated anode-free pouch cells achieve 350 W h kg-1 energy density and 97% capacity retention after 50 cycles.

Reliable impedance analysis of Li-ion battery half-cell by standardization on electrochemical impedance spectroscopy (EIS).

Electrochemical impedance spectroscopy (EIS) is a powerful characterization technique for the in-depth investigation of kinetic/transport parameters detection, reaction mechanism understanding, and degradation effects exploration in lithium-ion battery (LIB) systems. However, due to the lack of standardized criterion/paradigm, severe misinterpretations occur frequently during an EIS measurement. In this paper, the significance of instrumental accuracy is described and the character/principle of selection on the simulation model is illuminated/proposed, showing that an adequate precision device and an appropriate fitting model are a prerequisite for a correct EIS analysis. Moreover, the drawbacks of conventional two-electrode EIS experiments for typical coin-type cells are rigorously pointed out by comparison with the ideal three-electrode configuration, where the real impedance information of the cathode would be masked by the sum of both the anode film resistance response and the unavoidable inductive loop signal. The three-electrode case enables efficient accurate observations on individual electrodes, thus facilitating abundant and useful information acquisition. Consequently, devices with a sufficient accuracy, rational simulation models, and advanced three-electrode cells are distinctly illustrated as standardized criterion/paradigm for EIS characterizations, which are essentially important for electrode and interface modifications in LIBs.

New Dibenzo-α-pyrone Derivatives with α-Glucosidase Inhibitory Activities from the Marine-Derived Fungus Alternaria alternata.

Three new dibenzo-α-pyrone derivatives, alternolides A-C (1-3), and seven known congeners (4-10) were isolated from the marine-derived fungus of Alternaria alternata LW37 assisted by the one strain-many compounds (OSMAC) strategy. The structures of 1-3 were established by extensive spectroscopic analyses, and their absolute configurations were determined by modified Snatzke's method and electronic circular dichroism (ECD) calculations. Compounds 6 and 7 showed good 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant scavenging activities with IC50 values of 83.94 ± 4.14 and 23.60 ± 1.23 µM, respectively. Additionally, 2, 3 and 7 exhibited inhibitory effects against α-glucosidase with IC50 values of 725.85 ± 4.75, 451.25 ± 6.95 and 6.27 ± 0.68 µM, respectively. The enzyme kinetics study indicated 2 and 3 were mixed-type inhibitors of α-glucosidase with Ki values of 347.0 and 108.5 µM, respectively. Furthermore, the interactions of 2, 3 and 7 with α-glucosidase were investigated by molecular docking.

Titration Mass Spectroscopy (TMS): A Quantitative Analytical Technology for Rechargeable Batteries.

Development of high-energy-density rechargeable battery systems not only needs advanced qualitative characterizations for mechanism exploration but also requires accurate quantification technology to quantitatively elucidate products and fairly assess numerous modification strategies. Herein, as a reliable quantification technology, titration mass spectroscopy (TMS) is developed to accurately quantify O-related anionic redox reactions (Li-O2 battery and nickel-cobalt-manganese (NCM)/Li-rich cathodes), parasitic carbonate deposition and decomposition (derived from air-exposure degradation and electrolyte oxidation), and dead Li0 formation (Li-metal battery and over-discharged graphite anode). TMS technology can harvest key information on products (e.g., quantification of oxidized lattice oxygen and solid electrolyte interphase (SEI)/cathode electrolyte interphase (CEI) components) and guide corresponding design strategy by enhancing understanding of the mechanism (e.g., clearly distinguish the catalytic target of highly oxidative Ni4+ on the NCM cathode). Not limited as a rigid quantification tool for widely known products/mechanisms, TMS technology has been demonstrated as a powerful and versatile tool for the investigations of advanced batteries.

Effects of Tamoxifen vs. Toremifene on fatty liver development and lipid profiles in breast Cancer.

BACKGROUND: Tamoxifen (TAM) and Toremifene (TOR), two kinds of selective estrogen receptor modulators (SERMs), have equal efficacy in breast cancer patients. However, TAM has been proved to affect serum lipid profiles and cause fatty liver disease. The study aimed to compare the effects of TAM and TOR on fatty liver development and lipid profiles. METHODS: This study performed a retrospective analysis of 308 SERMs-treated early breast cancer patients who were matched 1:1 based on propensity scores. The follow-up period was 3 years. The primary outcomes were fatty liver detected by ultrasonography or computed tomography (CT), variation in fibrosis indexes, and serum lipid profiles change. RESULTS: The cumulative incidence rate of new-onset fatty liver was higher in the TAM group than in the TOR group (113.2 vs. 67.2 per 1000 person-years, p < 0.001), and more severe fatty livers occurred in the TAM group (25.5 vs. 7.5 per 1000 person-years, p = 0.003). According to the Kaplan-Meier curves, TAM significantly increased the risk of new-onset fatty liver (25.97% vs. 17.53%, p = 0.0243) and the severe fatty liver (5.84% vs. 1.95%, p = 0.0429). TOR decreased the risk of new-onset fatty liver by 45% (hazard ratio = 0.55, p = 0.020) and showed lower fibrotic burden, independent of obesity, lipid, and liver enzyme levels. TOR increased triglycerides less than TAM, and TOR increased high-density lipoprotein cholesterol, while TAM did the opposite. No significant differences in total cholesterol and low-density lipoprotein cholesterol are observed between the two groups. CONCLUSIONS: TAM treatment is significantly associated with more severe fatty liver disease and liver fibrosis, while TOR is associated with an overall improvement in lipid profiles, which supports continuous monitoring of liver imaging and serum lipid levels during SERM treatment.

Identification of novel potent HIV-1 inhibitors by exploiting the tolerant regions of the NNRTIs binding pocket.

With our previously identified potent NNRTIs 25a and HBS-11c as leads, series of novel thiophene[3,2-d]pyrimidine and thiophene[2,3-d]pyrimidine derivatives were designed via molecular hybridization strategy. All the target compounds were evaluated for their anti-HIV-1 activity and cytotoxicity in MT-4 cells. Compounds 16a1 and 16b1 turned out to be the most potent inhibitors against WT and mutant HIV-1 strains (L100I, K103N, and E138K), with EC50 values ranging from 0.007 µM to 0.043 µM. Gratifyingly, 16b1 exhibited significantly reduced cytotoxicity (CC50 > 217.5 µM) and improved water solubility (S = 49.3 µg/mL at pH 7.0) compared to the lead 25a (S < 1 µg/mL at pH 7.0, CC50 = 2.30 µM). Moreover, molecular docking was also conducted to rationalize the structure-activity relationships of these novel derivatives and to understand their key interactions with the binding pocket.

Long Non-Coding RNA NLIPMT as a Tumor Suppressor and Inhibitor of Cell Proliferation and Metastasis in Papillary Thyroid Carcinoma.

INTRODUCTION: Gene expression association studies of tumor samples have uncovered several long non-coding RNAs (lncRNAs) closely related to various types of cancer. Several lncRNAs have been reported to play essential roles in the progression of papillary thyroid carcinoma (PTC). Novel lncRNA inhibiting proliferation and metastasis (lnc-NLIPMT) is a known regulator of mammary cell proliferation and motility, but its involvement in PTC is unclear. MATERIALS AND METHODS: We investigated the role of lnc-NLIPMT in PTC by quantitative real-time polymerase chain reaction (qRT-PCR) on various PTC tissue samples and cell lines. We assessed the effects of overexpression or knockdown of lnc-NLIPMT on the proliferation, migration, and invasion of PTC cells using CCK-8, cell clone formation, and transwell assays. Changes in the expression of N-cadherin and vimentin were detected by immunoblotting. RESULTS: Our results revealed a downregulation of the expression of lnc-NLIPMT in PTC and a negative correlation between lnc-NLIPMT expression and tumor size (P=0.006). Overexpression of lnc-NLIPMT in TPC-1 and B-CPAP cells significantly suppressed cell proliferation, migration, and invasion, while lnc-NLIPMT knockdown had the opposite effect. In addition, lnc-NLIPMT played an important role in the regulation of the expression of N-cadherin and vimentin. CONCLUSION: lnc-NLIPMT inhibits cell proliferation and metastasis of PTC cells and is a potential diagnostic and prognostic biomarker in PTC.

Overexpression of novel lncRNA NLIPMT inhibits metastasis by reducing phosphorylated glycogen synthase kinase 3ß in breast cancer.

Long noncoding RNAs (lncRNAs) are considered as regulators of gene expression in cancers. However, cancer profiling has little focused on noncoding genes. Here, we reported that RP11-115N4.1 (here renamed novel lncRNA inhibiting proliferation and metastasis [NLIPMT]) was downregulated in breast cancer tissues. Ectopic expression of NLIPMT inhibited mammary cell proliferation, motility in vitro. Moreover, lnc-NLIPMT reduced the growth of implanted MDA-MB-231 cells in vivo. Mechanistically, glycogen synthase kinase 3ß (GSK3ß) was identified as an effector protein regulated by lnc-NLIPMT. Inhibition of GSK3ß activity restored NLIPMT-induced inhibition of proliferation and motility in breast cancer cells. These data reveal that lnc-NLIPMT functions as a driver of breast cancer progression and might serve as a potential target for antimetastatic therapies.

Interactions between ALDH2 rs671 polymorphism and lifestyle behaviors on coronary artery disease risk in a Chinese Han population with dyslipidemia: A guide to targeted heart health management.

BACKGROUND: Both aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism and lifestyle behaviors are involved in coronary artery disease (CAD), while the interaction between them is currently unknown. METHODS: A nested case-control study was conducted in 161 patients with CAD and 495 controls in dyslipidemia population in Yinzhou District, Ningbo, Zhejiang Province, China, in August 2013. Anthropometric data and blood samples were collected, demographic characteristics and lifestyle behaviors information were obtained by a face-to-face interview, dietary intake was assessed by a food frequency questionnaire, and genomic DNA was genotyped. RESULTS: Carriers with increasing number of A alleles had an elevated CAD risk compared with G allele carriers (adjusted OR = 1.483, 95% CI = 1.114-1.974). Carriers of rs671 A/G and A/A genotypes had a higher CAD risk than carriers of G/G genotype (adjusted OR = 1.492, 95% CI = 1.036-2.148). Similarly, individuals with rs671 A/A genotype had a higher CAD risk than individuals with A/G and G/G genotypes (adjusted OR = 2.161, 95% CI = 1.139-4.101). We found a borderline additive interaction between regular fried food intake and A/A and A/G genotypes, and a significantly additive interaction between sedentary/light physical activity and A/A and A/G genotypes. CONCLUSIONS: Individuals with A/A or A/G genotypes of rs671 have a higher CAD risk, if they lack physical activity and take fried food regularly, than individuals with G/G genotypes. These findings can help to provide a guide to targeted heart health management.