JIMR: Joint Semantic and Geometry Learning for Point Scene Instance Mesh Reconstruction.

Point scene instance mesh reconstruction is a challenging task since it requires both scene-level instance segmentation and instance-level mesh reconstruction from partial observations simultaneously. Previous works either adopt a detection backbone or a segmentation one, and then directly employ a mesh reconstruction network to produce complete meshes from incomplete instance point clouds. To further boost the mesh reconstruction quality with both local details and global smoothness, in this work, we propose JIMR, a joint framework with two cascaded stages for semantic and geometry understanding. In the first stage, we propose to perform both instance segmentation and object detection simultaneously. By making both tasks promote each other, this design facilitates subsequent mesh reconstruction by providing more precisely-segmented instance points and better alignment benefiting from predicted complete bounding boxes. In the second stage, we propose a complete-then-reconstruct procedure, where the completion module explicitly disentangles completion from reconstruction, and enables the usage of pre-trained weights of existing powerful completion and reconstruction networks. Moreover, we propose a comprehensive confidence score to filter proposals considering the quality of instance segmentation, bounding box detection, semantic classification, and mesh reconstruction at the same time. Experiments show that our proposed JIMR outperforms state-of-the-art methods regarding instance reconstruction qualitatively and quantitatively.

Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m6A Methylation.

Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68+ cell number and the levels of iNOS, TNF-α, IL-1ß (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

Relationship between dietary live microbe intake and the prevalence of COPD in adults: a cross-sectional study of NHANES 2013-2018.

OBJECTIVE: To explore the potential association between dietary live microbes and the prevalence of Chronic Obstructive Pulmonary Diseases (COPD). METHODS: In this cross-sectional study, data of 9791 participants aged 20 years or older in this study were collected from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018. Participants in this study were classified into three groups according to the Sanders' dietary live microbe classification system: low, medium, and high dietary live microbe groups. COPD was defined by a combination of self-reported physician diagnoses and standardized medical status questionnaires. Logistic regression and subgroup analysis were used to assess whether dietary live microbes were associated with the risk of COPD. RESULTS: Through full adjustment for confounders, participants in the high dietary live microbe group had a low prevalence of COPD in contrast to those in low dietary live microbe group (OR: 0.614, 95% CI: 0.474-0.795, and p < 0.001), but no significant association with COPD was detected in the medium and the low dietary live microbe groups. This inverse relationship between dietary live microbe intake and COPD prevalence was more inclined to occur in smokers, females, participants aged from 40 to 59 years old and non-obese participants. CONCLUSION: A high dietary live microbe intake was associated with a low prevalence of COPD, and this negative correlation was detected especially in smokers, females, participants aged from 40 to 59 years old and non-obese participants.

Visualization and Quantification of Drug Release by GSH-Responsive Multimodal Integrated Micelles.

Using molecular imaging techniques to monitor biomarkers and drug release profiles simultaneously is highly advantageous for cancer diagnosis and treatment. However, achieving the accurate quantification of both biomarkers and drug release with a single imaging modality is challenging. This study presents the development of a glutathione (GSH)-responsive polymer-based micelle, PEG-SS-FCy7/PEG-SS-GEM (PSFG), which can precisely localize the tumor using bimodal imaging and prevent drug leakage. These PSFG micelles exhibit a small particle size of 106.3 ± 12.7 nm with a uniform size distribution, and the drug loading efficiency can also be easily controlled by changing the PEG-SS-FCy7 (PSF) and PEG-SS-GEM (PSG) feeding ratio. The PSFG micelles display weak fluorescence emission and minimal drug release under physiological conditions but collapse in the presence of GSH to trigger near-infrared fluorescence and the 19F magnetic resonance imaging signal, allowing for real-time monitoring of intracellular GSH levels and drug release. GSH could synergistically promote the disassembly of the micellar structure, resulting in accelerated probe and drug release of up to about 93.1% after 24 h. These prodrug micelles exhibit high in vitro and in vivo antitumor abilities with minimal side effects. The GSH-responsive drug delivery system with dual-modal imaging capability provides a promising imaging-guided chemotherapeutic platform to probe the tumor microenvironment and quantify real-time drug release profiles with minimal side effects.

Serum inflammatory markers as prognostic marker for nasopharyngeal carcinoma with liver metastasis: a multi-center retrospective study.

BACKGROUND: This retrospective study investigated the prognostic value of serum inflammatory markers in nasopharyngeal carcinoma (NPC) patients, focusing on their association with overall survival (OS) and liver metastasis-free survival (LMFS). METHODS: The study included 314 NPC patients treated between 2010 and 2020. Clinical characteristics, treatment methods, and serum inflammatory markers were assessed. Patients were categorized into two groups of with and without liver metastasis. Univariate and multivariate Cox regression and Kaplan-Meier survival analyses were performed to investigate the prognostic value of serum inflammatory markers in NPC patients with and without liver metastasis. RESULTS: In the whole cohort, univariate Cox regression analysis singled out tumor necrosis factor-α (TNF-α) (HR = 1.57, 95% CI 1.44-4.90, p = 0.004) and neutrophil-to-lymphocyte ratio (NLR) (HR = 2.13, 95% CI 1.33-3.99, p = 0.009), which were significantly associated with poorer OS. In patients with liver metastasis, TNF-α and NLR could not independently predict OS. However, high TNF-α levels were independently associated with worse OS in patients without liver metastasis (HR (95% CI) = 2.75 (1.67-8.68), p < 0.001). High NLR levels could independently predict poor OS in both groups with (HR (95% CI) = 1.94 (1.77-6.38), p = 0.010) and without liver metastasis (HR (95% CI) = 1.58 (1.19-7.54), p = 0.009). Ultimately, TNF-α and NLR could not significantly predict LMFS. CONCLUSION: This study highlights the prognostic significance of TNF-α and NLR in NPC patients, especially in those with liver metastasis. These inflammatory markers could serve as valuable indicators for assessing the prognosis of NPC patients. Further research is warranted to validate their clinical utility and explore potential therapeutic implications.

Uric acid-driven NLRP3 inflammasome activation triggers lens epithelial cell senescence and cataract formation.

Excessive uric acid (UA) is associated with age-related cataract. A previous study showed that a high UA level in the aqueous humor stimulated the senescence of lens epithelial cells (LECs), leading to cataract progression. To better understand the underlying mechanisms, we investigated UA-driven senescence in human lens tissue samples obtained during surgery, rat lens organ cultures, and in vivo experiments, using senescence-associated ß-galactosidase (SA-ß-gal) staining, electronic microscopy, Western blotting, and histological analyses. Initially, we identified markedly higher expressions of NLRP3 and caspase-1 in the lens capsules of hyper-uricemic patients compared to normo-uricemic patients. This increase was accompanied by a significant rise in the SA-ß-gal positive rate. We next built a cataract model in which rat lenses in an organ culture system were treated with an increasing dosage of UA. Notably, opacification was apparent in the lenses treated with 800 µM of UA starting on the fifth day. Mechanistically, UA treatment not only significantly induced the expression of NLRP3, caspase-1, and IL-1ß, but also upregulated the levels of SA-ß-gal and the senescence regulators p53 and p21. These effects were fully reversed, and lens opacification was ameliorated by the addition of MCC950, a selective NLRP3 antagonist. Moreover, an in vivo model showed that intravitreal UA injection rapidly induced cataract phenotypes within 21 days, an effect significantly mitigated by co-injection with MCC950. Together, our findings suggest that targeting the UA-induced NLRP3 inflammasome with MCC950 could be a promising strategy for preventing cataract formation associated with inflammageing.

Fabrication and characterization of salidroside W/O/W emulsion with sodium alginate.

Salidroside (Sal), the main bioactive substance in Rhodiola rosea, is a promising functional food component with a wide range of pharmacological effects, but its biological activity is challenging to sustain due to its short half-life, low oral bioavailability, and susceptibility to environmental factors. The aim of this study was to investigate the effect of sodium alginate (SA) concentration on the construction of W/O/W emulsion in the protection of Sal. With the escalation of SA concentrations, the range of droplet size distribution was smaller and the droplets were more uniform. When the concentration of SA was 2 %, the average droplet size reached 9.1 ± 0.1 µm, and the encapsulation efficiency of Sal was 77.8 ± 1.8 %. Moreover, the double emulsion with 2 % SA was the most stable for 28 days at 4 °C since the oil droplets were embedded in the network structure of SA.

[Air Microbial Contamination and Risk of Respiratory Exposure of Workers in Chicken Farms].

Animal farms are important sources of microbial contamination in the air environment. However, there are few reports on the time-regularity characteristics of airborne microbial contamination in farms. In the context of this situation, a study was conducted for more than 80 weeks using 16S rRNA gene amplicon sequencing to characterize the bacterial distribution and respiratory exposure in the farm air and fecal environment, respectively, taking a layer farm as an example. The results showed that 16S rRNA concentrations in air and manure samples ranged from 6.08×105-4.90×106 copies·m-3 and 4.27×108-1.15×1010 copies·g-1, respectively. The mean values of airborne bacterial concentrations were significantly higher in winter than in summer, whereas the biodiversity showed the opposite trend. The dominant bacterial phylum in both air and manure in the layer farm was Firmicutes. During the investigated time, the top three dominant genera in the air were relatively stable, in the order of Lactobacillus, Bacteroides, and Faecalibacterium, whereas the dominant genera in feces fluctuated with the increase in breeding time. The correlation between the community structure of bacteria and pathogenic bacteria in both air and manure was not significant, but the concentrations of both target microorganisms in different media were significantly correlated. The bioaerosolization index of bacteria in manure showed an increasing trend with increasing breeding time, whereas the opposite trend was observed for pathogenic bacteria. In this case, [Ruminococcus]_torques_group, Bacteroides, and Faecalibacterium were the top three pathogenic genera that were the most prone to aerosolization. There were seasonal differences in bacterial respiratory exposures of chicken farm workers, with mean intake values of 2.54×107 copies·d-1 and 2.87×105 copies·d-1 for bacteria and pathogenic bacteria, respectively. The results of this study will provide a scientific basis for systematically assessing the contamination characteristics and potential health risks of airborne microorganisms on farms and for developing corresponding industry standards for occupational exposure and prevention and control measures.

Design and experiment of high-field asymmetric waveform ion mobility spectrometry chip based on an integrated temperature control printed circuit board structure.

RATIONALE: During the detection of volatile organic compounds (VOC) using high-field asymmetric waveform ion mobility spectrometry (FAIMS), the ambient temperature significantly impacts the accuracy of planar FAIMS. To mitigate the influence of ambient temperature on detection accuracy and enhance resolution, a FAIMS system based on the inner impedance characteristics of a printed circuit board (PCB) was designed for temperature control. METHODS: This study, conducted under standard atmospheric pressure, aimed to assess the signal stability of a planar FAIMS instrument with and without temperature control, and the effect of temperature change on the detection ability of acetone, ethanol, and their mixture was studied using PCB self-heating. RESULTS: Experimental results demonstrated that the base noise in FAIMS with temperature control was 0.2 pA, whereas that in FAIMS without temperature control was 1.8 pA. Notably, with increasing temperature, the detection ability of FAIMS changes accordingly. The optimal relative detection ability of acetone was observed when the electrode plate was heated to 45°C under an electric field of 15 kV/cm. CONCLUSIONS: This study provides a novel approach to improve the resolving power of FAIMS systems and their signal-to-noise ratio. The utilization of a PCB-based temperature control proved effective in stabilizing FAIMS signal characteristics and optimizing detection capabilities, particularly for VOCs such as acetone. These findings have significant implications for improving the accuracy and resolving power of FAIMS systems in VOC detection applications.

Ultralong Nanowires of Cadmium Phosphate Hydroxide Synthesized Using a Cadmium Oleate Precursor Hydrothermal Method and Sulfidation Conversion to Ultralong CdS Nanowires.

Ultralong nanowires with ultrahigh aspect ratios exhibit high flexibility, and they are promising for applications in various fields. Herein, a cadmium oleate precursor hydrothermal method is developed for the synthesis of ultralong nanowires of cadmium phosphate hydroxide. In this method, water-soluble cadmium salt is used as the cadmium source, water-soluble phosphate is used as the phosphorus source, and sodium oleate is adopted as a reactant to form cadmium oleate precursor and as a structure-directing agent. By using this method, ultralong nanowires of cadmium phosphate hydroxide are successfully synthesized using CdCl2, sodium oleate, and NaH2PO4 as reactants in an aqueous solution by hydrothermal treatment at 180 °C for 24 h. In addition, a new type of flexible fire-resistant inorganic paper with good electrical insulation performance is fabricated using ultralong nanowires of cadmium phosphate hydroxide. As an example of the extended application of this synthetic method, ultralong nanowires of cadmium phosphate hydroxide can be converted to ultralong CdS nanowires through a convenient sulfidation reaction. In this way, ultralong CdS nanowires are successfully synthesized by simple sulfidation of ultralong nanowires of cadmium phosphate hydroxide under mild conditions. The as-prepared ultralong nanowires of cadmium phosphate hydroxide are promising for applications as the precursors and templates for synthesizing other inorganic ultralong nanowires and have wide applications in various fields.

Salt-rejecting 3D cone flowing evaporator based on bilayer photothermal paper for high-performance solar seawater desalination.

Solar energy-driven water evaporation technology is a promising, low-cost and sustainable approach to alleviate the global clean water shortage, but usually suffers from low water evaporation rate and severe salt deposition on the water evaporation surface. In this work, a hydrophilic bilayer photothermal paper-based three-dimensional (3D) cone flowing evaporator was designed and prepared for stable high-performance seawater desalination with excellent salt-rejecting ability. The as-prepared bilayer photothermal paper consisted of MXene (Ti3C2Tx) and HAA (ultralong hydroxyapatite nanowires, poly(acrylic acid), and poly(acrylic acid-2-hydroxyethyl ester)). The accordion-like multilayered MXene acted as the efficient solar light absorber, and ultralong hydroxyapatite (HAP) nanowires served as the thermally insulating and supporting skeleton with a porous networked structure. A siphon effect-driven unidirectional fluid transportation unit in the 3D cone flowing evaporator could guide the concentrated saline flowing away from the evaporating surface to prevent salt deposition on the evaporation surface, avoiding severe deterioration of the performance in solar water evaporation. Furthermore, combining high solar light absorption and high photothermal conversion efficiencies, low water evaporation enthalpy (1838 ±â€¯11 J g-1), and additional energy taken from the ambient environment, the as-prepared cone flowing evaporator exhibited a high water evaporation rate of 3.22 ±â€¯0.20 kg m-2 h-1 for real seawater under one sun illumination (1 kW m-2), which was significantly higher than many values reported in the literature. This study provides an effective approach for designing high-performance solar energy-driven water evaporators for sustainable seawater desalination and wastewater purification.

Exudate-Induced Gelatinizable Nanofiber Membrane with High Exudate Absorption and Super Bactericidal Capacity for Bacteria-Infected Wound Management.

Invasion of bacteria and continuous oozing of exudate are significant causes of interference with the healing of infected wounds. Therefore, an exudate-induced gelatinizable and near-infrared (NIR)-responsive nanofiber membrane composed of polyvinyl alcohol (PVA), carboxymethyl chitosan (CMC), and Fe-doped phosphomolybdic acid (Fe-PMA) with exceptional exudate absorption capacity and potent bactericidal efficacy is developed and denoted as the PVA-FP-CMC membrane. After absorbing exudate, the fiber membrane can transform into a hydrogel membrane, forming coordination bonds between the Fe-PMA and CMC. The unique exudate-induced gelation process imparts the membrane with high exudate absorption and retention capability, and the formed hydrogel also traps the bacteria that thrive in the exudate. Moreover, it is discovered for the first time that the Fe-PMA exhibits an enhanced photothermal conversion capability and photocatalytic activity compared to the PMA. Therefore, the presence of Fe-PMA provides the membrane with a photothermal and photodynamic therapeutic effect for killing bacteria. The PVA-FP-CMC membrane is proven with a liquid absorption ratio of 520.7%, a light-heat conversion efficiency of 41.9%, high-level generation of hydroxyl radical (•OH) and singlet oxygen (1O2), and a bacterial killing ratio of 100% for S. aureus and 99.6% for E. coli. The treatment of infected wounds on the backs of rats further confirms the promotion of wound healing by the PVA-FP-CMC membrane with NIR irradiation. Overall, this novel functional dressing for the synergistic management of bacteria-infected wounds presents a promising therapeutic strategy for tissue repair and regeneration.

California's zero-emission vehicle adoption brings air quality benefits yet equity gaps persist.

Zero-emission vehicle (ZEV) adoption is a key climate mitigation tool, but its environmental justice implications remain unclear. Here, we quantify ZEV adoption at the census tract level in California from 2015 to 2020 and project it to 2035 when all new passenger vehicles sold are expected to be ZEVs. We then apply an integrated traffic model together with a dispersion model to simulate air quality changes near roads in the Greater Los Angeles. We found that per capita ZEV ownership in non-disadvantaged communities (non-DACs) as defined by the state of California is 3.8 times of that in DACs. Racial and ethnic minorities owned fewer ZEVs regardless of DAC designation. While DAC residents receive 40% more pollutant reduction than non-DACs due to intercommunity ZEV trips in 2020, they remain disproportionately exposed to higher levels of traffic-related air pollution. With more ZEVs in 2035, the exposure disparity narrows. However, to further reduce disparities, the focus must include trucks, emphasizing the need for targeted ZEV policies that address persistent pollution burdens among DAC and racial and ethnic minority residents.

[Expression and significance of jumonji domain-containing protein 2B and hypoxia inducible factor-1α in non-Hodgkin lymphoma tissues in children]. / 含jumonji结构域的蛋白2Bå’Œç¼ºæ°§è¯±å¯¼å› å­1α在儿童非霍奇金淋巴瘤组织中的表达及意义.

OBJECTIVES: To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children. METHODS: Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed. RESULTS: The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (rs=0.333, P=0.024). CONCLUSIONS: JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.

Poly[bis-(O-ethyl-hydroxy-laminium) [di-µ-chlorido-di-chlorido-cadmate(II)]].

The title compound, {(CH3CH2ONH3)2[CdCl4]}n, consists of bilayers of organic CH3CH2ONH3 + cations and infinite [CdCl4]n 2n- inorganic layers. It can be described as an organic-inorganic hybrid layered perovskite. In the crystal structure, the CdII cation is situated at an inversion center and is coordinated by six chloride ions, forming a slightly distorted octa-hedral coordination polyhedron. By corner-sharing of the [CdCl6] octa-hedra, infinite [CdCl4]n 2n- inorganic layers are formed, extending parallel to (100). The inorganic layers alternate with bilayers of CH3CH2ONH3 + cations, whereby the connection of the cationic and anionic layers is achieved through N-H⋯Cl hydrogen bonds and Coulombic inter-actions.

Safety and feasibility of modified duct-to-mucosa pancreaticojejunostomy during pancreatoduodenectomy: A retrospective cohort study.

BACKGROUND: Pancreatoduodenectomy (PD) is the most effective surgical procedure to remove a pancreatic tumor, but the prevalent postoperative complications, including postoperative pancreatic fistula (POPF), can be life-threatening. Thus far, there is no consensus about the prevention of POPF. AIM: To determine possible prognostic factors and investigate the clinical effects of modified duct-to-mucosa pancreaticojejunostomy (PJ) on POPF development. METHODS: We retrospectively collected and analyzed the data of 215 patients who underwent PD between January 2017 and February 2022 in our surgery center. The risk factors for POPF were analyzed by univariate analysis and multivariate logistic regression analysis. Then, we stratified patients by anastomotic technique (end-to-side invagination PJ vs modified duct-to-mucosa PJ) to conduct a comparative study. RESULTS: A total of 108 patients received traditional end-to-side invagination PJ, and 107 received modified duct-to-mucosa PJ. Overall, 58.6% of patients had various complications, and 0.9% of patients died after PD. Univariate and multivariate logistic regression analyses showed that anastomotic approaches, main pancreatic duct (MPD) diameter and pancreatic texture were significantly associated with the incidence of POPF. Additionally, the POPF incidence and operation time in patients receiving modified duct-to-mucosa PJ were 11.2% and 283.4 min, respectively, which were significantly lower than those in patients receiving traditional end-to-side invagination PJ (27.8% and 333.2 minutes). CONCLUSION: Anastomotic approach, MPD diameter and pancreatic texture are major risk factors for POPF development. Compared with traditional end-to-side invagination PJ, modified duct-to-mucosa PJ is a simpler and more efficient technique that results in a lower incidence of POPF. Further studies are needed to validate our findings and explore the clinical applicability of our technique for laparoscopic and robotic PD.

Exceptional structural phase transition near room temperature in an organic-inorganic hybrid ferroelectric.

An organic-inorganic hybrid ferroelectric, (C6H5CH2CH2NH3)2[HgI4], undergoes an exceptional structural phase transition near room temperature, triggered by a flip of half the organic cations and an order-disorder transition of the inorganic anions, and may be regarded as a displacive-type ferroelectric. This finding provides a new structural phase transition mechanism in molecule-based ferroelectrics.

An NIR Fluorescence Turn-on and MRl Bimodal Probe for Concurrent Real-time in vivo Sensing and Labeling of ß-Galactosidase.

To realize sensing and labeling biomarkers is quite challenging in terms of designing multimodal imaging probes. In this study, we developed a novel ß-galactosidase (ß-gal) activated bimodal imaging probe that combines near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) to enable real-time visualization of activity in living organisms. Upon ß-gal activation, Gal-Cy-Gd-1 exhibits a remarkable 42-fold increase in NIR fluorescence intensity at 717 nm, allowing covalent labeling of adjacent target enzymes or proteins and avoiding molecular escape to promote probe accumulation at the tumor site. This fluorescence reaction enhances the longitudinal relaxivity by approximately 1.9 times, facilitating high-resolution MRI. The unique features of Gal-Cy-Gd-1 enable real-time and precise visualization of ß-gal activity in live tumor cells and mice. The probe's utilization aids in identifying in situ ovarian tumors, offering valuable assistance in the precise removal of tumor tissue during surgical procedures in mice. The fusion of NIR fluorescence and MRI activation through self-immobilizing target enzymes or proteins provides a robust approach for visualizing ß-gal activity. Moreover, this approach sets the groundwork for developing other activatable bimodal probes, allowing real-time in vivo imaging of enzyme activity and localization.

Augmenting Immunotherapy via Bioinspired MOF-Based ROS Homeostasis Disruptor with Nanozyme-Cascade Reaction.

Despite its remarkable clinical breakthroughs, immune checkpoint blockade (ICB) therapy remains limited by the insufficient immune response in the "cold" tumor. Nanozyme-based antitumor catalysis is associated with precise immune activation in the tumor microenvironment (TME). In this study, a cascade-augmented nanoimmunomodulator (CMZM) with multienzyme-like activities, which includes superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione oxidase (GSHOx), that dissociates under an acidic and abundant GSH TME, is proposed for multimodal imaging-guided chemodynamic therapy (CDT)/photodynamic therapy (PDT) enhanced immunotherapy. Vigorous multienzyme-like activities can not only produce O2 to alleviate hypoxia and promote the polarization of M2 to M1 macrophages, but also generate ROS (•OH and 1 O2 ) and deplete GSH in the TME to expose necrotic cell fragments and reverse immunosuppressive TME by eliciting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes (CTLs) in tumors. Therefore, inhibitory effects on both primary and distant tumors are achieved through synergy with an α-PD-L1 blocking antibody. This cascade multienzyme-based nanoplatform provides a smart strategy for highly efficient ICB immunotherapy against "cold" tumors by revising immunosuppressive TME.

Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.

Backgrounds: The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons. Methods: This network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework. Results: Nine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups. Conclusion: In patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient's profiles to maximize safety. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022334644.