A Tumor Environment-Activated Photosensitized Biomimetic Nanoplatform for Precise Photodynamic Immunotherapy of Colon Cancer.

Aggressive nature of colon cancer and current imprecise therapeutic scenarios simulate the development of precise and effective treatment strategies. To achieve this, a tumor environment-activated photosensitized biomimetic nanoplatform (PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM) is fabricated by encapsulating metal-organic framework loaded with developed photosensitizer PEG2000-SiNcTI-Ph and immunoadjuvant CpG oligodeoxynucleotide within fusion cell membrane expressing programmed death protein 1 (PD-1) and cluster of differentiation 47 (CD47). By stumbling across, systematic evaluation, and deciphering with quantum chemical calculations, a unique attribute of tumor environment (low pH plus high concentrations of adenosine 5'-triphosphate (ATP))-activated photodynamic effect sensitized by long-wavelength photons is validated for PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM, advancing the precision of cancer therapy. Moreover, PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM evades immune surveillance to target CT26 colon tumors in mice mediated by CD47/signal regulatory proteins α (SIRPα) interaction and PD-1/programmed death ligand 1 (PD-L1) interaction, respectively. Tumor environment-activated photodynamic therapy realized by PEG2000-SiNcTI-Ph/CpG-ZIF-8@CM induces immunogenic cell death (ICD) to elicit anti-tumor immune response, which is empowered by enhanced dendritic cells (DC) uptake of CpG and PD-L1 blockade contributed by the nanoplatform. The photodynamic immunotherapy efficiently combats primary and distant CT26 tumors, and additionally generates immune memory to inhibit tumor recurrence and metastasis. The nanoplatform developed here provides insights for the development of precise cancer therapeutic strategies.

Crystal Structure Regulation of CoSe2 Induced by Fe Dopant for Promoted Surface Reconstitution toward Energetic Oxygen Evolution Reaction.

Most nonoxide catalysts based on transition metal elements will inevitably change their primitive phases under anodic oxidation conditions in alkaline media. Establishing a relationship between the bulk phase and surface evolution is imperative to reveal the intrinsic catalytic active sites. In this work, it is demonstrated that the introduction of Fe facilitates the phase transition of orthorhombic CoSe2 into its cubic counterpart and then accelerates the Co-Fe hydroxide layer generation on the surface during electrocatalytic oxygen evolution reaction (OER). As a result, the Fe-doped cubic CoSe2 catalyst exhibits a significantly enhanced activity with a considerable overpotential decrease of 79.9 and 66.9 mV to deliver 10 mA·cm-2 accompanied by a Tafel slope of 48.0 mV·dec-1 toward OER when compared to orthorhombic CoSe2 and Fe-doped orthorhombic CoSe2, respectively. Density functional theory (DFT) calculations reveal that the introduction of Fe on the surface hydroxide layers will tune electron density around Co atoms and raise the d-band center. These findings will provide deep insights into the surface reconstitution of the OER electrocatalysts based on transition metal elements.

Flower-shaped 2D crystals grown in curved fluid vesicle membranes.

The morphologies of two-dimensional (2D) crystals, nucleated, grown, and integrated within 2D elastic fluids, for instance in giant vesicle membranes, are dictated by an interplay of mechanics, permeability, and thermal contraction. Mitigation of solid strain drives the formation of crystals with vanishing Gaussian curvature (i.e., developable domain shapes) and, correspondingly, enhanced Gaussian curvature in the surrounding 2D fluid. However, upon cooling to grow the crystals, large vesicles sustain greater inflation and tension because their small area-to-volume ratio slows water permeation. As a result, more elaborate shapes, for instance, flowers with bendable but inextensible petals, form on large vesicles despite their more gradual curvature, while small vesicles harbor compact planar crystals. This size dependence runs counter to the known cumulative growth of strain energy of 2D colloidal crystals on rigid spherical templates. This interplay of intra-membrane mechanics and processing points to the scalable production of flexible molecular crystals of controllable complex shape.

Retrogradation behaviors of damaged wheat starch with different water contents.

The retrogradation behaviors of five damaged wheat starches (DS) after milling 0, 30, 60, 90, and 120 min with different water contents (33, 50, 60 %) were evaluated. Milling treatment increased DS content and developed an agglomeration of small particles. After 7 days of storage, the recrystallinity and long-range ordered structure of starch pastes were increased with the contents of DS and water. This process led to a lower setback viscosity and poor leaching of amylose. LF-NMR indicated a conversion from tightly bound water and free water to weakly bound water. During storage, DS12 with 60 % water content had the highest retrogradation tendency where the retrogradation enthalpy increased by 1.5 J/g and 2.2 J/g compared with DS0 with 60 % and DS12 with 33 % water content. DS with higher water content promoted the water mobility and made the starch molecular chains migrated conveniently. These changes facilitated the recrystallinity process during retrogradation period.

Insight into the promoted recrystallization and water distribution of bread by removing starch granule - surface and - associated proteins during storage.

The influence of starch granule surface proteins (SGSPs) and starch granule-associated proteins (SGAPs) on bread retrogradation was investigated in a reconstituted dough system. The removal of both SGSPs and SGAPs resulted in poor bread qualities, decreasing specific volume and crumb porosity, leading to more baking loss and compact crumb structure. Particularly, removing SGSPs was effective in promoting the bread retrogradation. After 7 days of storage, the hardness of bread without SGSPs showed an increase of 353.34 g than the bread without SGAPs. Proton population and relaxation times exhibited that the absence of SGSPs significantly decreased the content of bound water from 11.51 % to 7.03 %, indicating lower water-holding capacity due to the loosen gelling structure. Compared to the control group, bread without SGSPs accelerated the starch recrystallinity by a reduction in soluble starch content, thereby increasing the retrogradation enthalpy and relative crystallinity through promoting the molecular reassociation in starch.

Two new species of Sordariomycetes (Chaetomiaceae and Nectriaceae) from China.

Rich and diverse fungal species occur in different habitats on the earth. Many new taxa are being reported and described in increasing numbers with the advent of molecular phylogenetics. However, there are still a number of unknown fungi that have not yet been discovered and described. During a survey of fungal diversity in different habitats in China, we identified and proposed two new species, based on the morphology and multi-gene phylogenetic analyses. Herein, we report the descriptions, illustrations and molecular phylogeny of the two new species, Bisifusariumkeratinophilumsp. nov. and Ovatosporasinensissp. nov.

Regulating the defects of MIL-101(Cr) for the efficient and simultaneous determination of eleven plant growth regulators in fresh fruit juice.

This work presents an efficient sorbent for plant growth regulators (PGRs) by regulating the defects of a metal-organic framework MIL-101(Cr). Using the regulated MIL-101(Cr), we developed a simple and effective method for the simultaneous determination of eleven PGRs in fresh fruit juice. The extraction conditions were optimized by an orthogonal array design. Under optimal conditions, the method showed a satisfactory limit of detection (0.1-1.2 ng/g), recovery rates (83.4-110.2 %), and precision (2.9-18.0 % for intra-day and 2.7-10.8 % for inter-day), as well as a greatly suppressed matrix effect. Notably, regulating the defects significantly enhanced the desorption of PGRs on MIL-101(Cr). The sorbent didn't need to be destroyed to release the adsorbed PGRs and could be reused at least 6 times. Furthermore, the defects of MIL-101(Cr) and interactions between the sorbent and PGRs were studied by TGA, ATR-IR, XPS, NH3-TPD and UV-Vis DRS.

Label-free and highly-sensitive detection of calcium ions using a silicon-on-sapphire light-addressable potentiometric sensor.

BACKGROUND: Ionic calcium (Ca2+) plays a crucial role in maintaining normal physiological and biochemical functions within the human body. Detecting the concentration of Ca2+ is of utmost significance for various purposes, including disease screening, cellular metabolism research, and evaluating drug effectiveness. However, current detection approaches such as fluorescence and colorimetry face limitations due to complex labeling techniques and the inability to track changes in Ca2+ concentration. In recent years, extensive research has been conducted in this field to explore label-free and efficient approaches. RESULTS: In this study, a novel light-addressed potentiometric sensor (LAPS) using silicon-on-sapphire technology, has been successfully developed for Ca2+ sensing. The Ca2+-sensitive LAPS achieved a wide-range detection of Ca2+, ranging from 10-2 M to 10-7 M, with an impressive detection limit of 100 nM. These advancements are attributed to the ultra-thin silicon layer, silicon dioxide layer, and solid-state silicon rubber sensitive membrane around 6 µm. Furthermore, the sensor demonstrated the ability to dynamically monitor fluctuations in Ca2+ concentration ranging from 10-9 M to 10-2 M within a solution. Its remarkable selectivity, specificity, and long-term stability have facilitated its successful application in the detection of Ca2+ in human serum and urine. SIGNIFICANCE AND NOVELTY: This work presents a Ca2+-sensitive sensor that combines a low detection limit and a wide detection range. The development represents the emergence of a label-free and rapid Ca2+ detection tool with immense prospects in home-based health monitoring, community disease screening, as well as cellular metabolism, and drug screening evaluations.

Copper Metabolism and Cuproptosis: Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases.

Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, the human body maintains copper homeostasis. Copper deficiency or excess can adversely affect cellular function. Therefore, copper homeostasis is stringently regulated. Recent studies suggest that copper can trigger a specific form of cell death, namely, cuproptosis, which is triggered by excessive levels of intracellular copper. Cuproptosis induces the aggregation of mitochondrial lipoylated proteins, and the loss of iron-sulfur cluster proteins. In neurodegenerative diseases, the pathogenesis and progression of neurological disorders are linked to copper homeostasis. This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases. This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Triple Cascade Quantum-Strip for Heart Failure Point-of-Care Testing.

Heart failure (HF) is a life-threatening syndrome. Timely and accurate bedside monitoring of the occurrence and progression of HF via measurements of multiple HF-related biomarkers remains a challenge. Here, we report a triple cascade quantum-strip (TCQS) sensing strategy for the rapid and selective multiplex-tracing of three clinically validated HF biomarkers (BNP/NT-proBNP/ST2) in serum. High selectivity to the three biomarkers is achieved by controlling the individual recognition ability of three target-specific quantum immunoprobes and tuning their simultaneous use to BNP/NT-proBNP/ST2 recognition without mutual interference, which allows the three biomarkers to be directly enriched from serum samples. Benefiting from the fast release-binding kinetics of target-bound immunoprobes on TCQS, recognizable fluorescent signals can be rapidly read out through combining with a self-designed smartphone-based portable reader. This rapid and simple profiling strategy results in good specificity and sensitivity with LODs of 0.097, 0.072, and 0.948 ng/mL for BNP, NT-proBNP, and ST2, respectively, which match the need of clinical applications. Real serum samples are tested with an accuracy of 92.86% for HF diagnosis, validating the capability of the smartphone-read TCQS for practical applications. In particular, the simultaneous detection of the TCQS sensing strategy for BNP/NT-proBNP/ST2 will facilitate the accurate monitoring of HF occurrence, risk stratification, progression, and prognosis as a powerful POCT tool.

VDAC1, as a downstream molecule of MLKL, participates in OGD/R-induced necroptosis by inducing mitochondrial damage.

Ischemia-reperfusion (I/R) injury constitutes a significant risk factor for a range of diseases, including ischemic stroke, myocardial infarction, and trauma. Following the restoration of blood flow post-tissue ischemia, oxidative stress can lead to various forms of cell death, including necrosis, apoptosis, autophagy, and necroptosis. Recent evidence has highlighted the crucial role of mitochondrial dysfunction in I/R injury. Nevertheless, there remains much to be explored regarding the molecular signaling network governing cell death under conditions of oxidative stress. Voltage-dependent anion channel 1 (VDAC1), a major component in the outer mitochondrial membrane, is closely involved in the regulation of cell death. In a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R), which effectively simulates I/R injury in vitro, our study reveals that OGD/R induces VDAC1 oligomerization, consequently exacerbating cell death. Furthermore, we have revealed the translocation of mixed lineage kinase domain-like protein (MLKL) to the mitochondria, where it interacts with VDAC1 following OGD/R injury, leading to an increased mitochondrial membrane permeability. Notably, the inhibition of MLKL by necrosulfonamide hinders the binding of MLKL to VDAC1, primarily by affecting the membrane translocation of MLKL, and reduces OGD/R-induced VDAC1 oligomerization. Collectively, our findings provide preliminary evidence of the functional association between MLKL and VDAC1 in the regulation of necroptosis.

The association between serum testosterone level and congestive heart failure in US male adults: data from National Health and Nutrition Examination Survey (NHANES) 2011-2016.

BACKGROUND: This study aimed to investigate the relationship between serum testosterone levels and the risk of congestive heart failure (CHF) in adult males. Previous research has suggested a potential link between serum testosterone and cardiovascular health, but the findings have been inconclusive. METHODS: This study was cross-sectional, and the data were obtained from the 2011-2016 cycle of the National Health and Nutrition Examination Survey (NHANES), which included a sample of 6,841 male participants. Serum testosterone levels were measured using a standardized assay, and CHF status was assessed through self-reporting. Covariates such as age, ethnicity, lifestyle factors, and health conditions were considered in the analysis. RESULTS: Among the participants, 242 individuals had a documented history of CHF. We observed a linear correlation between serum testosterone levels and CHF occurrence, with higher serum testosterone levels associated with a decreased risk of CHF (Q4 vs. Q1, OR = 0.29, 95% CI: 0.19-0.47, P < 0.001). After adjusting for confounding variables, multivariate analysis revealed that high serum testosterone levels remained significantly associated with a lower risk of CHF (OR: 0.47, 95% CI: 0.27-0.80, P = 0.01). Subgroup analysis indicated a significant association between high serum testosterone levels and reduced CHF risk in individuals over 50 years old. CONCLUSION: Our findings suggest that the serum testosterone level was positively associated with CHF in adult males. This study highlights the potential role of serum testosterone in cardiovascular health, particularly in older individuals. Further research is needed to elucidate the underlying mechanisms and explore the clinical implications of these findings.

Trends in suicide mortality among prostate cancer survivors in the United States, 1975-2019.

BACKGROUND: Suicide was an important cause of death in prostate cancer. This study intended to investigate trends in suicide mortality among prostate cancer (PCa) survivors from 1975 to 2019 in the United States. METHOD: We identified PCa survivors from the Surveillance, Epidemiology, and End Results (SEER) program from January 1975 to December 2019. Standardized mortality rate (SMR) was calculated d to assess the relative risk of suicide in PCa survivors compared with the general men population. Poisson regression model was performed to test for trend of SMRs. The cumulative mortality rate of suicide was calculated to assess the clinical burden of suicide mortality. RESULTS: 7108 (0.2%) cases were death from suicide cause, and 2,308,923(65.04%%) cases recorded as dying from non-suicidal causes. Overall, a slightly higher suicide mortality rate among PCa survivors was observed compared with general male population (SMR: 1.15, 95%CI: 1.09-1.2). The suicide mortality rate declined significantly relative to the general population by the calendar year of diagnosis, from an SMR of 1.74(95%CI: 1.17-2.51) in 1975-1979 to 0.99(0.89-1.1) in 2015-2019 (Ptrend < 0.001). PCa survivors with aged over 84 years, black and other races, registered in registrations (including Utah, New Mexico, and Hawaii) failed to observe a decrease in suicide mortality (Ptrend > 0.05). The cumulative suicide mortality during 1975-1994 was distinctly higher than in 1995-2019(P < 0.001). CONCLUSION: The trend in suicide mortality declined significantly from 1975 to 2019 among PCa survivors compared with the general male population in the United States. Notably, part of PCa survivors had no improvement in suicide mortality, and additional studies in the future were needed to explore it.

Trends in suicide mortality among cancer survivors in the US, 1975-2020.

BACKGROUND: Suicide in cancer survivors is a major public health concern, but its trends and risk factors are not well understood. This study aimed to investigate the standardized mortality rate (SMR) and trends in suicide among cancer survivors in the United States. METHODS: Using data from the SEER-9 database and US Mortality data, we identified 3,684,040 cancer survivors diagnosed between 1975 and 2020. The SMR of suicide among cancer survivors was calculated, and Poisson regression analysis was used to evaluate trends in suicide risk. Subgroup analyses were performed based on age, gender, race, tumor site, and stage. A competing risk model was used to calculate the 10-year cumulative incidence of suicide. RESULTS: Among cancer survivors, the overall SMR of suicide was 1.49 (95%CI: 1.46-1.53) times higher than that of the general population in the US. The risk of suicide varied significantly by cancer site, with the highest risk found in patients with malignant respiratory system cancer. Overall, we observed a significant downward trend in the suicide mortality rate among cancer patients. The cumulative incidence of suicide mortality among cancer survivors across four study periods exhibited significant statistical differences (P<0.001). CONCLUSIONS: Our study highlights the need for targeted suicide prevention efforts for cancer survivors, particularly those diagnosed with respiratory system cancer. The trend of declining suicide mortality rates among cancer survivors is promising, but continued efforts are needed to understand and address the underlying risk factors.

The administration of rhBmal1 reduces sleep deprivation-induced anxiety and cognitive impairment in mice.

BACKGROUND: In mammals, circadian rhythms control metabolism, immunological response and reproductive processes. Bmal1 (brain and muscle Arnt-like protein-1) is a key element in the regulation of circadian rhythms. METHODS: This investigation explores the pathophysiological effects of sleep deprivation in a mouse model as well as the potential underlying mechanisms. A mouse sleep deprivation model was constructed using a modified multi-platform water environment method. The anxiety-like behaviours of mice were assessed by the open field test and elevated plus maze, and the cognitive function of mice was tested by the nest-building test. The expression levels of targeted genes were determined by Western blotting assay and RT-qPCR assay. RESULTS: We found that sleep deprivation profoundly enhanced anxiety levels and impaired cognitive function in mice. Sleep deprivation also reduced the expression levels of Bmal1 and BDNF (brain-derived neurotrophic factor) and increased oxidative stress in the hippocampus of mice. The intraperitoneal injection of human recombinant rhBmal1 protein alleviated sleep deprivation-induced anxiety and cognitive impairment, restored Bmal1 and BDNF levels, and reduced oxidative stress in the hippocampus of mice. CONCLUSIONS: rhBmal1 treatment might serve as a potential therapy for mitigating sleep deprivation-related unfavourable symptoms.

Simultaneous Detection of Citric Acid and Oxalic Acid Based on Dual Spectrum and Biomimetic Peroxidase for Urolithiasis Screening with a Fully Automatic Urine Analyzer.

Urolithiasis stands as a prevalent ailment within the urinary system, with hyperoxaluria and hypocitraturia being the most frequent manifestations characterized by excessive oxalic acid (OA) and deficient citric acid (CA) levels in urine. Detecting these compounds in urine quantitatively holds paramount importance for early urolithiasis screening. Existing methodologies fall short in achieving simultaneous and on-site identification of OA and CA, posing challenges for accurate urolithiasis screening. Addressing this concern, the study successfully accomplishes the concurrent identification of OA and CA in urine through a combination of dual-spectral analysis and biomimetic peroxidase utilization. Bovine serum albumin and dithiothreitol-modified copper nanoclusters (BSA-DTT-CuNCs) are employed as biomimetic peroxidases, effectively mitigating interference and enabling the simultaneous determination of OA and CA. The quantification range spans from 0 to 12 mm for OA and 0.5 to 2.5 mm for CA, with detection limits of 0.18 and 0.11 mm, respectively. To facilitate swift and on-location urine analysis, a fully automated urine analyzer (FAUA) is introduced that streamlines the process of biomarker pretreatment and identification within urine samples. Validation with real urine samples from urolithiasis patients demonstrates the method's diagnostic precision, highlighting the dual-spectral technique and analyzer's promising role in urolithiasis screening.

Vertical impedance electrode array for spatiotemporal dynamics monitoring of 3D cells under drug diffusion effect.

Although three-dimensional (3D) tumor models feature more accurate responses to drugs, the Matrigel scaffold affects the drug diffusion effect. Obtaining accurate drug spatiotemporal response characteristics is of great significance in the drug screening domain. However, the conventional cell-based sensors are difficult to perform spatiotemporal dynamics impedance monitoring of 3D cells and evaluate the anti-cancer pharmacological effect. Here, we proposed a biosensing platform involving a vertical impedance electrode array (VIEA) chip and a multichannel detection system. The platform can dynamically record 3D cell impedance in the vertical direction, which is consistent with time- and location-dependent drug penetration, closely related to spatiotemporal cell viability under drug effects. The subtle changes of impedance signals in different locations induced by drug diffusion can be detected, which demonstrates its high performance in drug systematic evaluation. The universal and high-content 3D cell biosensing platform is believed to have promising potential in pharmacodynamics investigation and preclinical drug screening.

Assessing the prognostic impact of prostatic urethra involvement and developing a nomogram for T1 stage bladder cancer.

PURPOSE: To investigate prognostic values of prostatic urethra involvement (PUI) and construct a prognostic model that estimates the probability of cancer-specific survival for T1 bladder cancer patients. METHOD AND MATERIALS: We investigated the national Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) to get patients diagnosed with T1 bladder cancer. An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Kaplan-Meier method with the log-rank test was applied to assess cancer-specific survival (CSS) and overall survival (OS). Moreover, the propensity score matching (PSM) and multivariable Cox proportional hazard model were performed. All patients were randomly divided into the development cohort and validation group at the ratio of 7:3. The performance of the model was internally validated by calibration curves and the concordance index (C-index). RESULTS: The PUI group had a lower survival rate of both CSS and overall survival OS before and after PSM when compared to non-involved patients (All P < 0.05). Multivariate analysis revealed a poor prognosis in the PUI group for cancer-specific mortality (CSM) and all-cause mortality (ACM) analyses before and after PSM (All P < 0.05). Seven variables, including age, surgery, radiotherapy, tumour size, PUI, and marital status, were incorporated in the final nomogram. The C-index in the development cohort was 0.715 (0.711-0.719), while it was 0.672 (0.667-0.677) in the validation group. Calibration plots for 3- and 5-year cancer-specific survival showed good concordance in the development and validation cohorts. CONCLUSIONS: PUI was an independent risk factor of ACM and CSM in T1 bladder cancer patients. In addition, a highly discriminative and precise nomogram that predicted the individualized probability of cancer-specific survival for patients with T1 bladder cancer was constructed.

Rare-earth hydroxide/MXene hybrid: a promising agent for near-infrared photothermy and magnetic resonance imaging.

Layered gadolinium hydroxide (LGdH) and Ti3C2 monolayers were assembled into a LGdH/Ti3C2 (GTC) hybrid. The hybrid demonstrated enhanced near-infrared (NIR) light absorption properties and superior photothermal performance. Moreover, the GTC hybrid achieved an excellent T1-weighted magnetic resonance imaging (MRI) effect.

Two new species of Samsoniella (Cordycipitaceae, Hypocreales) from the Mayao River Valley, Guizhou, China.

Samsoniella species have been often found in the forest habitat and rarely found in special karst eco-environments, such as Tiankeng, valleys and caves. In this research, eleven cordyceps specimens were collected from Mayao River Valley. A known species (S.haniana) and two new species (S.duyunensis and S.vallis) were established and described according to a multilocus phylogenetic analysis and morphological characteristics. Our results provide insight that the richness of Samsoniella species in karst eco-environments and further attention should be paid to entomopathogenic fungi in such habitats.