Phytochemicals targeting mitophagy: Therapeutic opportunities and prospects for treating Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder and the leading cause of age-related cognitive decline. Recent studies have established a close relationship between mitophagy and the pathogenesis of AD. Various phytochemicals have shown promising therapeutic effects in mitigating the onset and progression of AD. This review offers a comprehensive overview of the typical features of mitophagy and the underlying mechanisms leading to its occurrence in AD, highlighting its significance in the disease's pathogenesis and progression. Additionally, we examine the therapeutic mechanisms of synthetic drugs that induce mitophagy in AD. Finally, we summarize recent advances in research on phytochemicals that regulate mitophagy in the treatment of AD, potentially guiding the development of new anti-AD drugs.

Membrane protein MHZ3 regulates the on-off switch of ethylene signaling in rice.

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.

Clinical study on freehand of bicortical sacral screw fixation with the assistance of torque measurement device.

BACKGROUND: Sacral screw loosening is a typical complication after internal fixation surgery through the vertebral arch system. Bicortical fixation can successfully prevent screw loosening, and how improving the rate of bicortical fixation is a challenging clinical investigation. OBJECTIVE: To investigate the feasibility of improving the double corticality of sacral screws and the optimal fixation depth to achieve double cortical fixation by combining the torque measurement method with bare hands. METHODS: Ninety-seven cases of posterior lumbar internal fixation with pedicle root system were included in this study. Based on the tactile feedback of the surgeon indicating the expected penetration of the screw into the contralateral cortex of the sacrum, the screws were further rotated by 180°, 360°, or 720°, categorized into the bicortical 180° group, bicortical 360° group, and bicortical 720° group, respectively. Intraoperatively, the torque during screw insertion was recorded. Postoperatively, the rate of double-cortex engagement was evaluated at 7 days, and screw loosening was assessed at 1 year follow-up. RESULTS: The bicortical rates of the 180° group, 360° group, and 720° group were 66.13%, 91.18% and 93.75%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05).The rates of loosening of sacral screws in the 180° group, 360° group, and 720° group were 20.97%, 7.35% and 7.81%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05). The bicortical 360° group achieved a relatively satisfactory rate of dual cortical purchase while maintaining a lower rate of screw loosening. CONCLUSION: Manual insertion of sacral screws with the assistance of a torque measurement device can achieve a relatively satisfactory dual cortical purchase rate while reducing patient hospitalization costs.

Interconversion and functional composites of metal-organic frameworks and hydrogen-bonded organic frameworks.

Metal-organic frameworks (MOFs), an emerging class of highly ordered crystalline porous materials, possess structural tunability, high specific surface area, well-defined pores, and diverse pore environments and morphologies, making them suitable for various potential applications. Moreover, hydrogen-bonded organic frameworks (HOFs), constructed from organic molecules with complementary hydrogen-bonding patterns, are rapidly evolving into a novel category of porous materials due to their facile mild preparation conditions, solution processability, easy regeneration capability, and excellent biocompatibility. These distinctive advantages have garnered significant attention across diverse fields. Considering the inherent binding affinity between MOFs and HOFs along with the fact that many MOF linkers can serve as building blocks for constructing HOFs, their combination holds promise in creating functional materials with enhanced performance. This feature paper provides an introduction to the interconversion between MOFs and HOFs followed by highlighting the emerging applications of MOF-HOF composites. Finally, we briefly discuss the current challenges associated with future perspectives on MOF-HOF composites.

Green Solvent γ-Valerolactone (GVL) Facilitates Photocatalytic C-H Bond Activation.

Solvents can significantly influence chemical reactions in condensed phases. Their critical properties are increasingly recognized in various research domains such as organic synthesis and biomass valorization. However, in semiconductor photocatalysis, solvents are primarily viewed as mediums for dissolving and diffusing substances, with their potential beneficial effects on photocatalytic conversions often overlooked. Additionally, common photocatalysis solvents like acetonitrile (ACN) pose serious safety and environmental concerns. In this study, we demonstrate that novel and safe green solvents, such as γ-valerolactone (GVL), can significantly enhance the performance of semiconductor photocatalysis for C-H bond activation. Non-specific solvent-solute interactions are the primary contributors to increased photocatalytic activity in the self-coupling of benzylic compounds. Specifically, GVL's large dielectric constant and high refractive index lower the energy barrier for the rate-determining C-H bond activation step, facilitating a faster coupling reaction. The versatility of GVL is further demonstrated in reactions with multiple reagents and in various oxidation and reduction photocatalytic systems beyond classic C-H bond activation. This work not only pioneers the use of green solvents but also provides comprehensive insights for proper solvent selection in semiconductor photocatalysis.

HGF ameliorates cardiomyocyte apoptosis and inflammatory response in sepsis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.

OBJECTIVE: This study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). METHODS: Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. RESULTS: The outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. CONCLUSION: HGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.

Hippocampal SorCS2 overexpression represses chronic stress-induced depressive-like behaviors by promoting the BDNF-TrkB system.

BACKGROUND: Emerging data has demonstrated that in mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Thus, it is possible that SorCS2 plays a role in the pathophysiology of depression by regulating the BDNF-TrkB system. METHODS: In the present study, SorCS2 expression in different brain regions [hippocampus, medial prefrontal cortex (mPFC), hypothalamus, amygdala, ventral tegmental area (VTA), and nucleus accumbens (NAc)] was thoroughly investigated in the chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression. The changes in depressive-like behaviors, the hippocampal BDNF signaling cascade, and amounts of hippocampal immature neurons were further investigated after SorCS2 overexpression by microinjection of the adenovirus associated virus vector containing the coding sequence of mouse SorCS2 (AAV-SorCS2) into the hippocampus of mice exposed to CSDS or CUMS. RESULTS: It was found that both CSDS and CUMS significantly decreased the protein and mRNA expression of SorCS2 in the hippocampus but not in other brain regions. Chronic stress also notably downregulated the level of hippocampal SorCS2-TrkB binding in mice. In contrast, AAV-based genetic overexpression of hippocampal SorCS2 fully reversed the chronic stress-induced not only depressive-like behaviors but also decreased SorCS2-TrkB binding, BDNF signaling pathway, and amounts of immature neurons in the hippocampus of mice. CONCLUSION: All these results suggest that enhancing the hippocampal SorCS2 expression protects against chronic stress, producing antidepressant-like actions. Hippocampal SorCS2 may participate in depression neurobiology and be a potential antidepressant target. SIGNIFICANCE STATEMENT: Targeting of proteins to distinct subcellular compartments is essential for neuronal activity and modulated by VPS10P domain receptors which include SorCS2. In mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Our study is the first direct evidence preliminarily showing that SorCS2 plays a role in depression neurobiology. It was found that chronic stress induced not only depressive-like behaviors but also decreased SorCS2 expression in the hippocampus. Chronic stress did not affect SorCS2 expression in the mPFC, hypothalamus, amygdala, VTA, or NAc. In contrast, genetic overexpression of hippocampal SorCS2 prevented against chronic stress, producing antidepressant-like actions in mice. Thus, hippocampal SorCS2 is a potential participant underlying depression neurobiology and may be a novel antidepressant target. Our study may also extend the knowledge of the neurotrophic hypothesis of depression.

High-order layered self-assembled multicavity metal--organic capsules and anti-cooperative host-multi-guest chemistry.

The construction and application of metal-organic cages with accessible internal cavities have witnessed rapid development, however, the precise synthesis of complex metal-organic capsules with multiple cavities and achievement of multi-guest encapsulation, and further in-depth comprehension of host-multi-guest recognition remain a great challenge. Just like building LEGO blocks, herein, we have constructed a series of high-order layered metal-organic architectures of generation n (n = 1/2/3/4 is also the number of cavities) by multi-component coordination-driven self-assembly using porphyrin-containing tetrapodal ligands (like plates), multiple parallel-podal ligands (like clamps) and metal ions (like nodes). Importantly, these high-order assembled structures possessed different numbers of rigid and separate cavities formed by overlapped porphyrin planes with specific gaps. The host-guest experiments and convincing characterization proved that these capsules G2-G4 could serve as host structures to achieve multi-guest recognition and unprecedentedly encapsulate up to four C60 molecules. More interestingly, these capsules revealed negative cooperation behavior in the process of multi-guest recognition, which provides a new platform to further study complicated host-multi-guest interaction in the field of supramolecular chemistry.

Causal relationship between gut microbiota and puerperal sepsis: a 2-sample Mendelian randomization study.

Background: Some recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis. Methods: This study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p < 1.0 × 10-5. The inverse variance weighted (IVW) parameter was used as the primary method for MR and it was supplemented by other methods. Additionally, a set of sensitivity analytical methods, including the MR-Egger intercept, Mendelian randomized polymorphism residual and outlier, Cochran's Q and the leave-one-out tests were carried out to assess the robustness of our findings. Results: Our study found 3 species of gut microbiota, Lachnospiraceae FCS020, Lachnospiraceae NK4A136, and Ruminococcaceae NK4A214, to be associated with PS. The IVW method indicated an approximately 19% decreased risk of PS per standard deviation increase with Lachnospiraceae FCS020 (OR = 0.81; 95% CI 0.66-1.00, p = 0.047). A similar trend was also found with Lachnospiraceae NK4A136 (OR = 0.80; 95% CI 0.66-0.97, p = 0.024). However, Ruminococcaceae NK4A214 was positively associated with the risk of PS (OR = 1.33, 95% CI: 1.07-1.67, p = 0.011). Conclusion: This two-sample MR study firstly found suggestive evidence of beneficial and detrimental causal associations of gut microbiota on the risk of PS. This may provide valuable insights into the pathogenesis of microbiota-mediated PS and potential strategies for its prevention and treatment.

Biochar modulates intracellular electron transfer for nitrate reduction in denitrifying anaerobic methane oxidizing archaea.

Denitrifying anaerobic methane oxidizing (DAMO) archaea plays a significant role in simultaneously nitrogen removal and methane mitigation, yet its limited metabolic activity hinders engineering applications. This study employed biochar to explore its potential for enhancing the metabolic activity and nitrate reduction capacity of DAMO microorganisms. Sawdust biochar (7 g/L) was found to increase the nitrate reduction rate by 2.85 times, although it did not affect the nitrite reduction rate individually. Scanning electron microscopy (SEM) and fluorescence excitation-emission matrix (EEM) analyses revealed that biochar promoted microbial aggregation, and stimulated the secretion of extracellular polymeric substances (EPS). Moreover, biochar bolstered the redox capacity and conductivity of the biofilm, notably enhancing the activity of the electron transfer system by 1.65 times. Key genes involved in intracellular electron transport (Hdr, MHC, Rnf) and membrane transport proteins (BBP, ABC, NDH) of archaea were significantly up-regulated. These findings suggest that biochar regulates electrons generated by reverse methanogenesis to the membrane for nitrate reduction.

Achieving Long-Term Stability of Partial Nitrification and Autotrophic Denitrification in an MABR via Sulfide Dosing.

While partial nitrification (PN) has the potential to reduce energy for aeration, it has proven to be unstable when treating low-strength wastewater. This study introduces an innovative combined strategy incorporating a low rate of oxygen supply, pH control, and sulfide addition to selectively inhibit nitrite-oxidizing bacteria (NOB). This strategy led to a stable PN in a laboratory-scale membrane aerated biofilm reactor (MABR). Over a period of 260 days, the nitrite accumulation ratio exceeded 60% when treating synthetic sewage containing 50 mg NH4+-N/L. Through in situ activity testing and high-throughput sequencing, the combined strategy led to low levels of nitrite-oxidation activity (<5.5 mg N/m2 h), Nitrospira species (relative abundance <1%), and transcription of nitrite-oxidation genes (undetectable). The addition of sulfide led to simultaneous PN and autotrophic denitrification in the single-stage MABR, resulting in over 60% total inorganic nitrogen removal. Sulfur-based autotrophic denitrification consumed nitrite and inhibited NOB conversion of nitrite to nitrate. The combined strategy has potential to be applied in large-scale sewage treatment and deserves further exploration.

Giant Expanded Porous Metallo-Hexagons.

Molecular self-assembly is a widely recognized approach for fabricating biomimetic functional nanostructures. Here, we report the synthesis of two giant hollow coronoid-like supramolecular hexagons, H1 and H2. These hexagons feature large cavities, showcasing unique inner and outer hexagons fixed by specific connectivities for enhanced stability and high metal center density. H1 exhibits properties that can be transformed through the thermodynamic conversion of the metallopolymer formed by L1 and L2. With an edge length of 6.8 nm, H2 is one of the largest hexagons reported to date. 1D and 2D NMR, TEM, ESI-MS, and TWIM-MS experiments provided conclusive evidence for the composition and structure of the assembled hexagons. This work demonstrates the feasibility of constructing giant supramolecular architectures with precise control over their size and shape, opening up new possibilities for the design and synthesis of sophisticated supramolecules and nonbiological materials.

Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma.

As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.

Effect of IL-9 neutralising antibody on pyroptosis via SGK1/NF-κB/NLRP3/GSDMD in allergic rhinitis mice.

Allergic rhinitis is a common non-infectious inflammatory disease that affects approximately 15 % of people worldwide and has a complex and unclear aetiology. In recent years, pyroptosis has been found to play a role in the development of allergic rhinitis. IL-9, pyroptosis, serum and glucocorticoid-induced protein kinase 1 (SGK1), NOD-like receptor 3 (NLRP3), and nuclear factor kappa B (NF-κB) have been shown to influence each other. Herein, we aimed to explore the role of IL-9 neutralising antibody in pyroptosis involving IL-9, SGK1, NF-κB, and NLRP3 in allergic rhinitis. We observed a decrease in cytokines involved in pyroptosis and gasdermin D (GSDMD) compared with those in mice with allergic rhinitis. Further, phosphorylation of NF-κB/p65 decreased compared with that in mice with allergic rhinitis; NLRP3 and ASC also decreased, although the levels were higher than those in controls. SGK1 levels decreased compared with that in mice with allergic rhinitis and increased after using IL-9 neutralising antibodies, thus demonstrating its negative regulatory effects. The IL-9 neutralising antibody reduced the inflammatory and pyroptosis responses via SGK1 and NF-κB/NLRP3/GSDMD pathway. Our research results indicate that IL-9 regulates allergic rhinitis via the influence of SGK1 and NF-κB/NLRP3/GSDMD signalling pathway, providing new insights for developing novel drugs to treat allergic rhinitis.

Efficacy of expanded periurethral cleansing in reducing catheter-associated urinary tract infection in comatose patients: a randomized controlled clinical trial.

BACKGROUND: The effect of the periurethral cleansing range on catheter-associated urinary tract infection (CAUTI) occurrence remains unknown. The purpose of this study was to evaluate the efficacy of expanded periurethral cleansing for reducing CAUTI in comatose patients. METHODS: In this randomized controlled trial, eligible patients in our hospital were enrolled and allocated randomly to the experimental group (expanded periurethral cleansing protocol; n = 225) or the control group (usual periurethral cleansing protocol; n = 221). The incidence of CAUTI on days 3, 7, and 10 after catheter insertion were compared, and the pathogen results and influencing factors were analyzed. RESULTS: The incidences of CAUTI in the experimental and control groups on days 3, 7, and 10 were (5/225, 2.22% vs. 7/221, 3.17%, P = 0.54), (12/225, 5.33% vs. 18/221, 8.14%, P = 0.24), and (23/225, 10.22% vs. 47/221, 21.27%, P = 0.001), respectively; Escherichia coli and Candida albicans were the most common species in the two groups. The incidences of bacterial CAUTI and fungal CAUTI in the two groups were 11/225, 4.89% vs. 24/221, 10.86%, P = 0.02) and (10/225, 4.44% vs. 14/221, 6.33%, P = 0.38), respectively. The incidences of polymicrobial CAUTI in the two groups were 2/225 (0.89%) and 9/221 (4.07%), respectively (P = 0.03). The percentages of CAUTI-positive females in the two groups were 9.85% (13/132) and 29.52% (31/105), respectively (P < 0.05). The proportion of CAUTI-positive patients with diabetes in the experimental and control groups was 17.72% (14/79), which was lower than the 40.85% (29/71) in the control group (P < 0.05). CONCLUSION: Expanded periurethral cleansing could reduce the incidence of CAUTI, especially those caused by bacteria and multiple pathogens, in comatose patients with short-term catheterization (≤ 10 days). Female patients and patients with diabetes benefit more from the expanded periurethral cleansing protocol for reducing CAUTI.

Circular RNA circIL21R promotes cervical cancer cells proliferation and migration by sponging the miR-1205/PTBP1 axis.

Increasing research has shown that the abnormal expression of circRNAs is closely related to tumorigenesis, apoptosis, and patient prognosis in cervical cancer. This study aimed to reveal the procancer role of circIL21R in cervical cancer and investigate its related molecular mechanisms. Bioinformatics analysis revealed that circIL21R promotes the progression of cervical cancer via the miR-1205/PTBP1 axis. CircIL21R expression was significantly greater in tumor tissue than in adjacent normal tissue, and higher circIL21R expression indicated shorter survival. We applied MTS assays, EdU assays, and Transwell assays to show that the overexpression of circIL21R promoted cervical cancer cell proliferation and invasion. Mechanistically, circIL21R promoted the expression of PTBP1 by sponging miR-1205. Moreover, rescue assays confirmed that regulating the expression of miR-1205 or PTBP1 could reverse the tumorigenic effect caused by circIL21R overexpression. In addition, circIL21R promoted the tumorigenesis of cervical cancer in vivo. In summary, our study demonstrated that circIL21R was highly expressed in cervical cancer and upregulated PTBP1 expression by acting as a ceRNA for miR-1205, making outstanding contributions to several malignant biological processes in cervical cancers, such as growth, proliferation, and invasion. CircIL21R is a potential biomarker for the diagnosis and treatment of cervical cancer.

Enhancing Carrier Mobility in Monolayer MoS2 Transistors with Process-Induced Strain.

Two-dimensional electronic materials are a promising candidate for beyond-silicon electronics due to their favorable size scaling of electronic performance. However, a major challenge is the heterogeneous integration of 2D materials with CMOS processes while maintaining their excellent properties. In particular, there is a knowledge gap in how thin film deposition and processes interact with 2D materials to alter their strain and doping, both of which have a drastic impact on device properties. In this study, we demonstrate how to utilize process-induced strain, a common technique extensively applied in the semiconductor industry, to enhance the carrier mobility in 2D material transistors. We systematically varied the tensile strain in monolayer MoS2 transistors by iteratively depositing thin layers of high-stress MgOx stressor. At each thickness, we combined Raman spectroscopy and transport measurements to unravel and correlate the changes in strain and doping within each transistor with their performance. The transistors displayed uniform strain distributions across their channels for tensile strains of up to 0.48 ± 0.05%, at 150 nm of stressor thickness. At higher thicknesses, mechanical instability occurred, leading to nonuniform strains. The transport characteristics systematically varied with strain, with enhancement in electron mobility at a rate of 130 ± 40% per % strain and enhancement of the channel saturation current density of 52 ± 20%. This work showcases how established CMOS technologies can be leveraged to tailor the transport in 2D transistors, accelerating the integration of 2D electronics into a future computing infrastructure.

3D-Printed Carbon Nanoneedle Electrodes for Dopamine Detection in Drosophila.

In vivo electrochemistry in small brain regions or synapses requires nanoelectrodes with long straight tips for submicron scale measurements. Nanoelectrodes can be fabricated using a Nanoscribe two-photon printer, but annealed tips curl if they are long and thin. We propose a new pulling-force strategy to fabricate a straight carbon nanoneedle structure. A micron-width bridge is printed between two blocks. The annealed structure shrinks during pyrolysis, and the blocks create a pulling force to form a long, thin, and straight carbon bridge. Parameterization study and COMSOL modeling indicate changes in the block size, bridge size and length affect the pulling force and bridge shrinkage. Electrodes were printed on niobium wires, insulated with aluminum oxide, and the bridge cut with focused ion beam (FIB) to expose the nanoneedle tip. Annealed needle diameters ranged from 400 nm to 5.25 µm and length varied from 50.5 µm to 146 µm. The electrochemical properties are similar to glassy carbon, with good performance for dopamine detection with fast-scan cyclic voltammetry. Nanoelectrodes enable biological applications, such as dopamine detection in a specific Drosophila brain region. Long and thin nanoneedles are generally useful for other applications such as cellular sensing, drug delivery, or gas sensing.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer.

As a highly invasive malignancy, esophageal cancer (EC) is a global health issue, and was the eighth most prevalent cancer and the sixth leading cause of cancer-related death worldwide in 2020. Due to its highly immunogenic nature, emer-ging immunotherapy approaches, such as immune checkpoint blockade, have demonstrated promising efficacy in treating EC; however, certain limitations and challenges still exist. In addition, tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment (TIME); thus, understanding the TIME is urgent and crucial, especially given the im-portance of an immunosuppressive microenvironment in tumor progression. The aim of this review was to better elucidate the mechanisms of the suppressive TIME, including cell infiltration, immune cell subsets, cytokines and signaling pathways in the tumor microenvironment of EC patients, as well as the downregulated expression of major histocompatibility complex molecules in tumor cells, to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies. Therefore, personalized treatments could be developed to maximize the advantages of immunotherapy.

Indian Ocean temperature anomalies predict long-term global dengue trends.

Despite identifying El Niño events as a factor in dengue dynamics, predicting the oscillation of global dengue epidemics remains challenging. Here, we investigate climate indicators and worldwide dengue incidence from 1990 to 2019 using climate-driven mechanistic models. We identify a distinct indicator, the Indian Ocean basin-wide (IOBW) index, as representing the regional average of sea surface temperature anomalies in the tropical Indian Ocean. IOBW is closely associated with dengue epidemics for both the Northern and Southern hemispheres. The ability of IOBW to predict dengue incidence likely arises as a result of its effect on local temperature anomalies through teleconnections. These findings indicate that the IOBW index can potentially enhance the lead time for dengue forecasts, leading to better-planned and more impactful outbreak responses.