High-frequency terahertz stimulation alleviates neuropathic pain by inhibiting the pyramidal neuron activity in the anterior cingulate cortex of mice.

Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7-10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximately 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions. In vivo and in vitro results demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex likely through enhancing the voltage-gated K+ and also the leak K+ conductance. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising applications in other nervous system diseases.

Up to 1 in 10 people are estimated to experience neuropathic pain, a particularly challenging form of chronic pain where nerve damage causes extreme sensitivity to everyday stimuli. Current treatments often rely on painkiller drugs that can lead to serious side effects as well as dependency issues. New and effective interventions are therefore necessary. One radically different approach is the use of 'terahertz' waves, a type of electromagnetic radiation that has the ability to affect the chemical bonds holding molecules together. In fact, previous research has shown that specific frequencies of terahertz waves can modify the activity of certain proteins. With this technique, it may therefore be possible to disrupt voltage-dependent potassium channels, a type of proteins which help to regulate nerve cell activity and is a possible target for pain therapy. To explore this approach, Peng, Wang, Tan et al. investigated whether high-frequency terahertz stimulation that targets potassium ion channels could reduce neuropathic pain in mice. The animals, which had undergone surgery recreating nerve damage, were implanted with a device that allowed the delivery of terahertz waves into a brain region vital for regulating pain sensations. Experiments showed that delivering 36 terahertz radiations changed important ion channel properties (such as how easily they would allow ions to pass through), decreasing neuron activity and raising the pain threshold of the mice. This finding indicates that, with further development, terahertz frequency stimulation could become a new, non-drug method to manage neuropathic pain. Additional research will be needed to see if terahertz waves could also be applied to other neurological disorders influenced by ion channel activity.

Molecular genetics, therapeutics and RET inhibitor resistance for medullary thyroid carcinoma and future perspectives.

Medullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy that accounts for approximately 1-2% of all thyroid cancers (TCs). MTC include hereditary and sporadic cases, the former derived from a germline mutation of rearrangement during transfection (RET) proto-oncogene, whereas somatic RET mutations are frequently present in the latter. Surgery is the standard treatment for early stage MTC, and the 10-year survival rate of early MTC is over 80%. While for metastatic MTC, chemotherapy showing low response rate, and there was a lack of effective systemic therapies in the past. Due to the high risk (ca. 15-20%) of distant metastasis and limited systemic therapies, the 10-year survival rate of patients with advanced MTC was only 10-40% from the time of first metastasis. Over the past decade, targeted therapy for RET has developed rapidly, bringing hopes to patients with advanced and progressive MTC. Two multi-kinase inhibitors (MKIs) including Cabozantinib and Vandetanib have been shown to increase progression-free survival (PFS) for patients with metastatic MTC and have been approved as choices of first-line treatment. However, these MKIs have not prolonged overall survival (OS) and their utility is limited due to high rates of off-target toxicities. Recently, new generation TKIs, including Selpercatinib and Pralsetinib, have demonstrated highly selective efficacy against RET and more favorable side effect profiles, and gained approval as second-line treatment options. Despite the ongoing development of RET inhibitors, the management of advanced and progressive MTC remains challenging, drug resistance remains the main reason for treatment failure, and the mechanisms are still unclear. Besides, new promising therapeutic approaches, such as novel drug combinations and next generation RET inhibitors are under development. Herein, we overview the pathogenesis, molecular genetics and current management approaches of MTC, and focus on the recent advances of RET inhibitors, summarize the current situation and unmet needs of these RET inhibitors in MTC, and provide an overview of novel strategies for optimizing therapeutic effects.

Synthetic Optimization and Antibacterial Activity of Novel Benzodioxepine-Biphenyl Amide Derivatives.

The biosynthesis of fatty acids constitutes a critical metabolic pathway in bacterial organisms. Prior investigations have highlighted the synthesis of antimicrobial compounds anchored in the benzodioxepin scaffold, noted for their pronounced antibacterial properties. Leveraging this foundational knowledge, the current research endeavors to meticulously engineer and synthesize a series of eight innovative benzodioxepin amide-biphenyl derivatives. This achievement was realized through the sophisticated optimization of synthetic methodologies. The scope of this study extends to a rigorous evaluation of the antibacterial prowess and biocompatibility of the aforementioned novel derivatives. Notably, Compound E4 emerged as a supremely potent antimicrobial agent. A detailed elucidation of the crystalline architecture of Compound E4 was conducted, alongside a thorough docking study to explore its interactions with the FabH enzyme.

AMAR-seq: Automated Multimodal Sequencing of DNA Methylation, Chromatin Accessibility, and RNA Expression with Single-Cell Resolution.

Parallel single-cell multimodal sequencing is the most intuitive and precise tool for cellular status research. In this study, we propose AMAR-seq to automate methylation, chromatin accessibility, and RNA expression coanalysis with single-cell precision. We validated the accuracy and robustness of AMAR-seq in comparison with standard single-omics methods. The high gene detection rate and genome coverage of AMAR-seq enabled us to establish a genome-wide gene expression regulatory atlas and triple-omics landscape with single base resolution and implement single-cell copy number variation analysis. Applying AMAR-seq to investigate the process of mouse embryonic stem cell differentiation, we revealed the dynamic coupling of the epigenome and transcriptome, which may contribute to unraveling the molecular mechanisms of early embryonic development. Collectively, we propose AMAR-seq for the in-depth and accurate establishment of single-cell multiomics regulatory patterns in a cost-effective, efficient, and automated manner, paving the way for insightful dissection of complex life processes.

Fingerprint Profiling of Glycans on Extracellular Vesicles via Lectin-Induced Aggregation Strategy for Precise Cancer Diagnostics.

Extracellular vesicles (EVs) harbor abundant glycans that mediate various functions, such as intercellular communication and disease advancement, which play significant roles in disease progression. However, the presence of EV heterogeneity in body fluids and the complex nature of the glycan structures have posed challenges for the detection of EV glycans. In this study, we provide a streamlined method integrated, membrane-specific separation with lectin-induced aggregation strategy (MESSAGE), for multiplexed profiling of EV glycans. By leveraging a rationally designed lectin-induced aggregation strategy, the expression of EV glycans is converted to size-based signals. With the assistance learning machine algorithms, the MESSAGE strategy with high sensitivity, specificity, and simplicity can be used for early cancer diagnosis and classification, as well as monitoring cancer metastasis via 20 µL plasma sample within 2 h. Furthermore, our platform holds promise for advancing the field of EV-based liquid biopsy for clinical applications, opening new possibilities for the profiling of EV glycan signatures in various disease states.

Fast Isolation and Sensitive Multicolor Visual Detection of Small Extracellular Vesicles by Multifunctional Polydopamine Nanospheres.

Small extracellular vesicles (sEVs) assume pivotal roles as vital messengers in intercellular communication, boasting a plethora of biological functions and promising clinical applications. However, efficient isolation and sensitive detection of sEVs continue to present formidable challenges. In this study, we report a novel method for fast isolation and highly sensitive multicolor visual detection of sEVs using aptamer-functionalized polydopamine nanospheres (SIMPLE). In the SIMPLE strategy, aptamer-functionalized polydopamine nanospheres (Apt-PDANS) with 170 nm diameters were synthesized and exhibited a remarkable ability to selectively bind to specific proteins on the surface of sEVs. The binding between sEVs and Apt-PDANS engenders an increase in the overall size of the sEVs, allowing fast isolation of sEVs by filtration (a filter membrane with a pore size of 200 nm). The fast isolation strategy not only circumvents the interference posed by unbound proteins and excessive probes as well as the intricacies associated with conventional ultracentrifugation methods but also expedites the separation of sEVs. Concurrently, the incorporation of Fe3+-doped PDANS permits the multicolor visual detection of sEVs, enabling quantitative analysis by the discernment of visual cues. The proposed strategy achieves a detection limit of 3.2 × 104 sEV mL-1 within 1 h, devoid of any reliance on instrumental apparatus. Furthermore, we showcase the potential application of this methodology in epithelial-mesenchymal transition monitoring and cancer diagnosis, while also envisioning its widespread adoption as a straightforward, rapid, sensitive, and versatile platform for disease monitoring and functional exploration.

DNA-DISK: Automated end-to-end data storage via enzymatic single-nucleotide DNA synthesis and sequencing on digital microfluidics.

In the age of information explosion, the exponential growth of digital data far exceeds the capacity of current mainstream storage media. DNA is emerging as a promising alternative due to its higher storage density, longer retention time, and lower power consumption. To date, commercially mature DNA synthesis and sequencing technologies allow for writing and reading of information on DNA with customization and convenience at the research level. However, under the disconnected and nonspecialized mode, DNA data storage encounters practical challenges, including susceptibility to errors, long storage latency, resource-intensive requirements, and elevated information security risks. Herein, we introduce a platform named DNA-DISK that seamlessly streamlined DNA synthesis, storage, and sequencing on digital microfluidics coupled with a tabletop device for automated end-to-end information storage. The single-nucleotide enzymatic DNA synthesis with biocapping strategy is utilized, offering an ecofriendly and cost-effective approach for data writing. A DNA encapsulation using thermo-responsive agarose is developed for on-chip solidification, not only eliminating data clutter but also preventing DNA degradation. Pyrosequencing is employed for in situ and accurate data reading. As a proof of concept, DNA-DISK successfully stored and retrieved a musical sheet file (228 bits) with lower write-to-read latency (4.4 min of latency per bit) as well as superior automation compared to other platforms, demonstrating its potential to evolve into a DNA Hard Disk Drive in the future.

Using terahertz spectroscopy to quantify bioactive flavonoids in Moxa Wool as predictor of rheumatoid arthritis treatment outcomes.

BACKGROUND: Moxibustion, a traditional Chinese medicine practice, employs Moxa Wool, derived from Artemisia argyi. Flavonoids, the key pharmacological constituents in Moxa Wool, are known for their anti-inflammatory and analgesic properties. The purity of Moxa Wool, particularly its flavonoid content, directly influences the efficacy of moxibustion treatments. However, quantifying these bioactive flavonoids accurately and non-destructively has been a challenge. PURPOSE: This study introduces terahertz spectroscopy as a non-destructive optical detection method for qualitative detection and quantitative analysis of flavonoids in Moxa Wool. By establishing a mathematical model between spectral signals and clinical efficacy, a reliable correlation between flavonoid concentration and the therapeutic effect of moxibustion can be established, providing a potential predictive model for the treatment outcomes of rheumatoid arthritis. STUDY DESIGN: We adopted terahertz spectroscopy technology and combined it with terahertz metamaterial biosensors to achieve rapid, efficient, and non-destructive testing of the quality of Moxa Wool. This method reduces the detection time from hours to minutes while lowering the sample detection limit, overcoming the limitations of traditional detection methods in pharmacological research. METHODS: Through terahertz metamaterial biosensors, rapid detection of the purity of Moxa Wool has been achieved. A combination of molecular simulation and terahertz spectroscopy was used to quantitatively analyze the flavonoid content in different purities of Moxa Wool. To ensure accuracy, the quantitative results of flavonoids obtained by terahertz spectroscopy were validated using high-performance liquid chromatography (HPLC). In addition, moxibustion treatment was performed on rats with rheumatoid arthritis using Moxa Wool, and medical indicator information was recorded. A mathematical analysis model was established to evaluate the correlation between flavonoid content and analgesic and anti-inflammatory effects. RESULTS: Terahertz spectroscopy analysis shows that there is a direct correlation between the flavonoid content in moxibustion and the absorption peak intensity. The maximum R2 in the model analysis is 0.98, indicating a high accuracy in predicting the purity of Moxa Wool. These results were also validated by HPLC. In a rat model, the purity of 30:1 Moxa Wool samples showed a 50 % decrease in TNF-α, IL-1ß, and IL-6 levels during treatment compared to low-purity samples, significantly reducing inflammation markers and pain symptoms. Meanwhile, The PLS prediction model established a correlation between terahertz-detected flavonoid levels and treatment outcomes (PWL and IL-1ß). The maximum R2 in the model is 0.91, indicating a high correlation between flavonoid levels and the anti-inflammatory and analgesic effects of moxibustion treatment. CONCLUSION: This study not only demonstrates the effectiveness of terahertz spectroscopy in the pharmacological quantification of bioactive compounds but also establishes a novel predictive model for the efficacy of moxibustion in rheumatoid arthritis treatment. It underscores the potential of integrating traditional medicine insights with advanced technology to enhance therapeutic strategies in pharmacology.

Eosinophils and drugs for eosinophilia are associated with the risk of colorectal cancer: a Mendelian randomization study.

Eosinophils have the potential to exhibit both anti-tumor properties and tumor-promoting effects. However, the impact of eosinophil levels in the bloodstream on tumorigenesis risk remains inadequately explored. Furthermore, investigations regarding the association between drugs regulating eosinophils and cancer risk are currently absent. In this study, we conducted a Mendelian randomization (MR) analysis utilizing eosinophil count and eosinophil percentage as exposures. In both cohorts, a significant association was observed between eosinophil count and the risk of colorectal cancer and skin malignancies. However, upon conducting a sensitivity analysis, heterogeneity was detected specifically in relation to skin malignancies. Subsequent reverse Mendelian randomization analysis did not indicate any evidence of reverse causality. Furthermore, the multivariate Mendelian randomization analysis results suggested that eosinophils act as a mediating factor in reducing the risk of colorectal cancer and skin malignancies in individuals with asthma. And the use of drugs that modulate eosinophilia may increase the risk of colorectal cancer. It is evident that the statistical evidence supporting a negative correlation between eosinophils count and the susceptibility to colorectal cancer is particularly robust. And, it is plausible to suggest that pharmaceutical interventions aimed at modulating eosinophilia may potentially heighten the risk of colorectal cancer. Hence, it is imperative to exercise caution and remain mindful of the potential risk of colorectal cancer when employing these medications.

Characterizing the Orderliness of Interfacial Water through Stretching Vibrations.

Spatial orderliness, which is the orderly structure of molecules, differs significantly between interfacial water and bulk water. Understanding this property is essential for various applications in both natural and engineered environments. However, the subnanometer thickness of interfacial water presents challenges for direct and rapid characterization of its structural orderliness. Herein, through molecular dynamics simulations and infrared spectral analysis of interfacial water in a graphene slit pore, we reveal a hyperbolic tangent relationship between the water ordering and its O-H stretching information in the infrared spectrum. Specifically, O-H symmetric stretching dominated in the highly ordered water structure, while a transition to the asymmetric stretching corresponded to an increase in the degree of disorder. Thus, the O-H stretching behavior could serve as a useful and quick assessment of the orderliness of interfacial water. This work provided insights into interfacial water's unique molecular network and structural dynamics and identified the stretching vibrations' key role in its degree of order, providing insight for fields such as nanotechnology, biology, and material science.

[Study on the Experimental Methodology of Plasma Clot Retraction].

OBJECTIVE: To explore the key factors affecting plasma clot retraction and optimize the experimental method of plasma clot retraction, in order to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction. METHODS: The effects of different concentrations of thrombin, Ca2 + and platelets on plasma clot retraction were studied, and the detection system of plasma clot retraction was optimized. The availability of the detection system was then validated by analyzing the regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction. RESULTS: Through the optimization study of multiple factors, platelet rich plasma (PRP) containing 0.5 mmol/L Ca2 + and 40×109/L platelets was treated with 0.2 U/ml thrombin to perform plasma clot retraction analysis. After treatment with thrombin for 15 min, plasma clot retracted significantly. After treatment with thrombin for 30 min, the percentage of plasma clot retraction was more than 50%. The regulatory effects of multiple signaling pathway inhibitors on plasma clot retraction were studied in this detection system. PKC inhibitor Go 6983 exhibited a significant inhibitory effect on plasma clot retraction, while PI3K inhibitor Ly294002 and p38 MAPK inhibitor SB203580 slightly suppressed plasma clot retraction. CONCLUSION: PRP containing 0.5 mmol/L Ca2 + and 40×109/L platelets can be induced with 0.2 U/ml thrombin to conduct plasma clot retraction analysis, which can be used to study the regulation of platelet function and evaluate the modulatory effects of drugs on plasma clot retraction.

Suicidal incidence and gender-based discrepancies in prolonged grief disorder: insights from a meta-analysis and systematic review.

Background: In the aftermath of bereavement, our research explores the subtleties of Prolonged Grief Disorder (PGD), focusing particularly on its correlation with suicidal behaviors and their variation across genders. This study seeks to elucidate the impact of gender on these behaviors among individuals suffering from PGD, thereby enhancing our understanding and facilitating the development of tailored therapeutic interventions. Methods: By November 24th, 2023, we had rigorously reviewed key databases such as PubMed, Web of Science, Cochrane Library, PsycINFO, and Embase. Independently, two researchers conducted detailed interviews and filled out questionnaires with participants to gather demographic information and record instances of prolonged grief disorder. The study also meticulously tracked occurrences of suicidal ideation, suicide attempts, suicide deaths, and self-injury among the participants. Results: The findings indicate that 22.34% of males reported suicidal ideation (95% CI: 21.33-23.35), a figure that rises to 26.84% among females (95% CI: 25.99-27.69). Notably, 12.11% of males attempted suicide (95% CI: 11.49-12.72), marginally surpassing the 9.60% observed in females (95% CI: 9.17-10.04). More striking disparities were observed in suicide deaths, with rates for males at 3.66% (95% CI: 3.32-4.00) compared to a notably higher 7.12% for females (95% CI: 6.44-7.81). Furthermore, the incidence of self-injury was lower among males, at 2.48% (95% CI: 2.03-2.94), than in females, who reported a rate of 5.09% (95% CI: 4.69-5.49). These patterns underscore the critical need for gender-specific interventions aimed at reducing these significant disparities. Conclusion: This study distinctly underscores the profound impact of gender on the manifestation of suicidal behaviors in individuals afflicted with prolonged grief disorder. It reveals that females are more prone to suicidal ideation, self-injury, and suicide deaths, while males predominantly exhibit a higher incidence of suicide attempts and risk-taking behaviors. These unmediated trends highlight the necessity for gender-specific clinical interventions tailored to address particular behaviors and modify prevalent patterns that typically resist conventional approaches. Systematic review registration: PROSPERO (york.ac.uk), identifier CRD42023480035.

Molecular genetics and research progress of uterine leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a type of malignant soft-tissue tumor, which is developed from myometrium in the female reproductive system. This disease is difficult to be distinguished from benign uterine leiomyoma in the early stages, but it progresses aggressively and relentlessly. Hence, uLMS has a dismal prognosis and high rates of both misdiagnosis and missed diagnosis. Unfortunately, current studies of uLMS pathogenesis and disease biology are inadequate. uLMS disease models are also very limited, hindering the development of effective therapeutics. In this review, we focus on the pathological molecular biology of uLMS, and systematically review the molecular genetic features, epigenetic variants, experimental models, and clinical research progress of uLMS. We further discuss the development direction and potential needs of uLMS in the fields of tumor evolution, tumor microenvironment, and tumor therapy, with the aim of providing a better understanding of the pathobiological mechanism of uLMS and providing a reference for the development of potential diagnostic and therapeutic strategies.

Combined traditional Chinese medicine therapy for the treatment of infertility with polycystic ovary syndrome: A network meta-analysis of randomized controlled trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) infertility has attracted great attention from researchers due to its high incidence. Numerous studies have shown that Chinese medicine is effective in treating this disease, but there is a wide variety of Chinese medicine therapies available, and there is a lack of comparative evaluation of the efficacy of various Chinese medicine combination therapies in the clinic, which requires further in-depth exploration. This study aims to evaluate the efficacy of a combined traditional Chinese medicine (TCM) therapy for the treatment of infertility with PCOS using network meta-analysis (NMA). METHODS: In PubMed, web of Science, Cochrane Library, Embase, China Knowledge Network, Wanfang Data, VIP Database, China Biomedical Literature Database (SinoMed) databases, searchs were conducted for information about the randomized controlled trials (RCTs) of combined TCM therapy for the treatment of infertility with PCOS. Quality evaluation was performed using the Cochrane 5.3 risk of bias assessment tool, and NMA using Stata 16.0. RESULTS: This study comprised 28 RCTs using 8 combined TCM therapies in total. The results of the NMA showed that moxibustion + herbal, fire acupuncture + herbal, acupuncture + herbal, electroacupuncture + herbal, and acupoint application + herbal improved the clinical pregnancy rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Additionally, ear point pressure + herbal enema + herbal, acupuncture and moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal improved the ovulation rate better than acupuncture, herbal, and western medicines monotherapy (P < .05). Moxibustion + herbal, fire acupuncture + herbal, and acupuncture + herbal are the 3 most effective therapies for improving the clinical pregnancy rate. Fire acupuncture + herbal, acupuncture + herbal, and ear point pressure + herbal enema + herbal are the 3 most effective therapies for improving the ovulation rate. CONCLUSION: The combined TCM therapy demonstrated better efficacy for the treatment of infertility with PCOS compared to acupuncture, herbal, and western medicines monotherapy. However, the optimal treatment therapy varied depending on the outcome indicators. Further large sample, high-quality, and standardized RCTs are needed to verify these findings.

Myeloid-derived suppressor cells-induced exhaustion of CD8 + T-cell participates in rejection after liver transplantation.

Liver transplantation (LT) rejection remains the most pervasive problem associated with this procedure, while the mechanism involved is still complicated and undefined. One promising solution may involve the use of myeloid-derived suppressor cells (MDSC). However, the immunological mechanisms underlying the effects of MDSC after LT remain unclear. This study is meant to clarify the role MDSCs play after liver transplantation. In this study, we collected liver tissue and peripheral blood mononuclear cells (PBMC) from LT patients showing varying degrees of rejection, as well as liver and spleen tissue samples from mice LT models. These samples were then analyzed using flow cytometry, immunohistochemistry and multiple immunofluorescence. M-MDSCs and CD8 + T-cells extracted from C57/BL6 mice were enriched and cocultured for in vitro experiments. Results, as obtained in both LT patients and LT mice model, revealed that the proportion and frequency of M-MDSC and PD-1 + T-cells increased significantly under conditions associated with a high degree of LT rejection. Within the LT rejection group, our immunofluorescence results showed that a close spatial contiguity was present between PD-1 + T-cells and M-MDSCs in these liver tissue samples and the proportion of CD84/PD-L1 double-positive M-MDSC was greater than that of G-MDSC. There was a positive correlation between the activity of CD84 and immunosuppressive function of M-MDSCs including PD-L1 expression and reactive oxygen species (ROS) production, as demonstrated in our in vitro model. M-MDSCs treated with CD84 protein were able to induce co-cultured CD8 + T-cells to express high levels of exhaustion markers. We found that CD84 regulated M-MDSC function via expression of PD-L1 through activation of the Akt/Stat3 pathway. These results suggest that the capacity for CD84 to regulate M-MDSC induction of CD8 + T-cell exhaustion may play a key role in LT rejection. Such findings provide important, new insights into the mechanisms of tolerance induction in LT.

Photo-to-Thermal Conversion Harnessing Low-Energy Photons Renders Efficient Solar CO2 Reduction.

Efficient photocatalytic solar CO2 reduction presents a challenge because visible-to-near-infrared (NIR) low-energy photons account for over 50% of solar energy. Consequently, they are unable to instigate the high-energy reaction necessary for dissociating C═O bonds in CO2. In this study, we present a novel methodology leveraging the often-underutilized photo-to-thermal (PTT) conversion. Our unique two-dimensional (2D) carbon layer-embedded Mo2C (Mo2C-Cx) MXene catalyst in black color showcases superior near-infrared (NIR) light absorption. This enables the efficient utilization of low-energy photons via the PTT conversion mechanism, thereby dramatically enhancing the rate of CO2 photoreduction. Under concentrated sunlight, the optimal Mo2C-C0.5 catalyst achieves CO2 reduction reaction rates of 12000-15000 µmol·g-1·h-1 to CO and 1000-3200 µmol·g-1·h-1 to CH4. Notably, the catalyst delivers solar-to-carbon fuel (STF) conversion efficiencies between 0.0108% to 0.0143% and the STFavg = 0.0123%, the highest recorded values under natural sunlight conditions. This innovative approach accentuates the exploitation of low-frequency, low-energy photons for the enhancement of photocatalytic CO2 reduction.

Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase.

BACKGROUND: Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B (CHB) patients were not previously conducted. AIM: To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy. METHODS: The clinical and laboratory data of 1532 untreated CHB patients were collected, and all patients had least once liver biopsy from January 2015 to December 2021. The significant differences among different phases of CHB infection were compared with t-test, and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis. RESULTS: Among 1532 untreated CHB patients, 814 (53.13%) patients were in the indeterminate phase. Significant liver histological changes (defined as biopsy score ≥ G2 and/or ≥ S2) were found in 488/814 (59.95%) CHB patients in the indeterminate phase. Significant liver histological changes were significant differences among different age, platelets (PLTs), and alanine aminotransferase (ALT) subgroup in indeterminate patient. Multivariate logistic regression analysis indicated that age ≥ 40 years old [adjust odd risk (aOR), 1.44; 95% confidence interval (CI): 1.06-1.97; P = 0.02], PLTs ≤ 150 × 109/L (aOR, 2.99; 95%CI: 1.85-4.83; P < 0.0001), and ALT ≥ upper limits of normal (aOR, 1.48; 95%CI: 1.08, 2.05, P = 0.0163) were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase. CONCLUSION: Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase, and additional strategies are urgently required for the management of these patients.

Computed Tomography-Based Intratumor Heterogeneity Predicts Response to Immunotherapy Plus Chemotherapy in Esophageal Squamous Cell Carcinoma.

RATIONALE AND OBJECTIVES: This study explored the intratumor heterogeneity (ITH) of esophageal squamous cell carcinoma (ESCC) using computed tomography (CT) and investigated the value of CT-based ITH in predicting the response to immune checkpoint inhibitor (ICI) plus chemotherapy in patients with ESCC. MATERIALS AND METHODS: This retrospective study included 416 patients with ESCC who received ICI plus chemotherapy at two independent hospitals between January 2019 and July 2022. Multiparametric CT features were extracted from ESCC lesions and screened using hierarchical clustering and dimensionality reduction algorithms. Logistic regression and machine learning models based on selected features were developed to predict treatment response and validated in separate datasets. ITH was quantified using the score calculated by the best-performing model and visualized through feature clustering and feature contribution heatmaps. A gene set enrichment analysis (GSEA) was performed to identify the biological pathways underlying the CT-based ITH. RESULTS: The extreme gradient boosting model based on CT-derived ITH had higher discriminative power, with areas under the receiver operating characteristic curve of 0.864 (95% confidence interval [CI]: 0.774-0.954) and 0.796 (95% CI: 0.698-0.893) in the internal and external validation sets. The CT-based ITH pattern differed significantly between responding and non-responding patients. The GSEA indicated that CT-based ITH was associated with immunity-, keratinization-, and epidermal cell differentiation-related pathways. CONCLUSION: CT-based ITH is an effective biomarker for identifying patients with ESCC who could benefit from ICI plus chemotherapy. Immunity-, keratinization-, and epidermal cell differentiation-related pathways may influence the patient's response to ICI plus chemotherapy.

Biomass-Derived Materials for Advanced Rechargeable Batteries.

Biomass-derived materials generally exhibit uniform and highly-stable hierarchical porous structures that can hardly be achieved by conventional chemical synthesis and artificial design. When used as electrodes for rechargeable batteries, these structural and compositional advantages often endow the batteries with superior electrochemical performances. This review systematically introduces the innate merits of biomass-derived materials and their applications as the electrode for advanced rechargeable batteries, including lithium-ion batteries, sodium-ion batteries, potassium-ion batteries, and metal-sulfur batteries. In addition, biomass-derived materials as catalyst supports for metal-air batteries, fuel cells, and redox-flow batteries are also included. The major challenges for specific batteries and the strategies for utilizing biomass-derived materials are detailly introduced. Finally, the future development of biomass-derived materials for advanced rechargeable batteries is prospected. This review aims to promote the development of biomass-derived materials in the field of energy storage and provides effective suggestions for building advanced rechargeable batteries.

Metabolic Labeling and Digital Microfluidic Single-Cell Sequencing for Single Bacterial Genotypic-Phenotypic Analysis.

Accurate assessment of phenotypic and genotypic characteristics of bacteria can facilitate comprehensive cataloguing of all the resistance factors for better understanding of antibiotic resistance. However, current methods primarily focus on individual phenotypic or genotypic profiles across different colonies. Here, a Digital microfluidic-based automated assay for whole-genome sequencing of single-antibiotic-resistant bacteria is reported, enabling Genotypic and Phenotypic Analysis of antibiotic-resistant strains (Digital-GPA). Digital-GPA can efficiently isolate and sequence antibiotic-resistant bacteria illuminated by fluorescent D-amino acid (FDAA)-labeling, producing high-quality single-cell amplified genomes (SAGs). This enables identifications of both minor and major mutations, pinpointing substrains with distinctive resistance mechanisms. Digital-GPA can directly process clinical samples to detect and sequence resistant pathogens without bacterial culture, subsequently provide genetic profiles of antibiotic susceptibility, promising to expedite the analysis of hard-to-culture or slow-growing bacteria. Overall, Digital-GPA opens a new avenue for antibiotic resistance analysis by providing accurate and comprehensive molecular profiles of antibiotic resistance at single-cell resolution.