Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

Disposable Peptidoglycan-Specific Biosensor for Noninvasive Real-Time Detection of Broad-Spectrum Gram-Positive Bacteria in Exhaled Breath Condensates.

Rapidly identifying and quantifying Gram-positive bacteria are crucial to diagnosing and treating bacterial lower respiratory tract infections (LRTIs). This work presents a field-deployable biosensor for detecting Gram-positive bacteria from exhaled breath condensates (EBCs) based on peptidoglycan recognition using an aptamer. Dielectrophoretic force is employed to enrich the bacteria in 10 s without additional equipment or steps. Concurrently, the measurement of the sensor's interfacial capacitance is coupled to quantify the bacteria during the enrichment process. By incorporation of a semiconductor condenser, the whole detection process, including EBC collection, takes about 3 min. This biosensor has a detection limit of 10 CFU/mL, a linear range of up to 105 CFU/mL and a selectivity of 1479:1. It is cost-effective and disposable due to its low cost. The sensor provides a nonstaining, culture-free and PCR-independent solution for noninvasive and real-time diagnosis of Gram-positive bacterial LRTIs.

Association of ADP­ribosylation factor family genes with prognosis and immune infiltration of breast cancer.

Breast cancer (BC) is the most common type of cancer found in women. ADP-ribosylation factors (ARFs) are a group of small proteins that bind to GTP and are involved in controlling different cellular functions. The function and evolution of multiple ARFs in BC have remained to be fully elucidated, despite existing studies on this protein family in Homo sapiens and other species. In the present study, a systematic analysis of ARF expression levels in BC tissues compared to normal breast tissues was performed using data from The Cancer Genome Atlas database. The analysis revealed significantly higher expression of ARFs in BC tissues. In addition, the prognostic significance of ARF1 and ARF3-6 expression levels was assessed in patients with BC. Of note, elevated ARF1 expression was associated with reduced rates of distant metastasis-free survival (DMFS), overall survival (OS) and recurrence-free survival (RFS) in affected individuals. Similarly, patients with high expression levels of ARF3 had lower post-progression survival (PPS) rates. In addition, patients with higher ARF4 expression had worse PPS and patients with high ARF5 expression exhibited lower DMFS. Patients with high ARF6 expression had worse DMFS, OS, RFS and predictive power score values. Furthermore, the expression of ARF was found to be strongly linked to the infiltration of various immune cell types, namely dendritic cells, macrophages, neutrophils, CD8+ T cells and B cells. These significant associations offer a solid foundation for the potential utilization of new therapeutic targets and predictive markers for the treatment of BC.

Eliminating the stabilizer antagonistic effects for efficiently stabilizing Pb and As co-contaminated soil by innovative stepwise steam flash heating.

Chemical stabilization is frequently used to stabilize lead (Pb) or arsenate (As), but faces challenges in Pb-As co-contaminated soils because of the antagonistic reactions between chemical stabilizers and contaminants. In this work, we innovated an effective and cost-efficient stepwise steam flash heating (SSFH) strategy to simultaneously immobilize Pb and As, and unraveled the underlying mechanisms. The combination of 1.5% Ca(H2PO4)2 and 2% Fe2(SO4)3 only decreased 1.99% Pb by toxicity characteristic leaching procedure (TCLP-Pb) but increased 17.8% of TCLP-As due to the antagonistic effects. SSFH with Ca(H2PO4)2 in the first step and Fe2(SO4)3 in the second step achieved the minimal TCLP-Pb and TCLP-As of 0.778 and 0.327 mg/L, respectively. It also reduced 69.8% of leachable As in 100-year acid rain simulation, indicating a favorable long-term stabilization performance. Additionally, SSFH approach reduced 43.2% stabilizer dosage and 14.9% cost. X-ray absorption near edge structure (XANES) documented that the stepwise SFH promoted the transformation of Pb(NO3)2 and NaAsO2/NaAsO3/As2O3/As2O5 into stable Pb3(PO4)2 and FeAsO4, preventing the formation of AsO43- and FePO4. Our findings proved the state-of-the-art SSFH approach and unraveled its mechanisms to stabilize Pb and As co-contamination in soils, offering a green and sustainable remediation alternative for the management of heavy metal contaminated sites. ENVIRONMENTAL IMPLICATION: A novel stepwise SFH approach can be applied to overcome the stabilizer antagonist effects by separately immobilizing Pb and As in two sequential steps. It also decreased 43.2% of stabilizer dosage and 14.9% of cost comparing to conventional chemical stabilization. This approach can be used for other metal co-contaminated soils facing similar antagonistic challenges, and our work raises a state-of-the-art solution for cost-effective, green and sustainable remediation practices.

Procrastination in the Intention-Behaviour Gap: Exercise Procrastination and the Moderating Role of Emotion.

Health behaviour procrastination is closely associated with the intention-behaviour gap. However, research on health behaviour procrastination has tended to focus on bedtime procrastination, with relatively few studies on exercise procrastination. This research examined the relationship between exercise procrastination and the intention-behaviour gap through three studies. Additionally, based on the temporal-affective self-regulation resource model, the moderating role of emotion as a self-regulatory resource in exercise procrastination was explored. Study 1 validated the Chinese version of the newly developed Procrastination in Exercise Scale in two Chinese adult samples (N = 2376 and N = 393). Study 2 collected two waves of data from 447 Chinese adults (Mage = 31.19) and examined the mediating role of exercise procrastination in the intention-behaviour gap. Using a sample of 453 Chinese adults (Mage = 20.39), Study 3 investigated the moderating role of positive and negative affect in the association between intention and exercise procrastination. Cross-lagged analyses revealed the predictive roles of Time 1 intention on Time 2 exercise procrastination and Time 1 exercise procrastination on Time 2 physical activity. Exercise procrastination mediated the relationship between intention and physical activity. Examining the moderating role of emotion between intention (Time 1) and exercise procrastination (Time 2), Study 3 found that negative affect buffered this association. Findings highlight the role of exercise procrastination in explaining the intention-behaviour gap and shed new light on physical activity interventions, with implications for promoting exercise behaviour.

Discovery of LC-MI-3: A Potent and Orally Bioavailable Degrader of Interleukin-1 Receptor-Associated Kinase 4 for the Treatment of Inflammatory Diseases.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a promising therapeutic target in inflammation-related diseases. However, the inhibition of IRAK4 kinase activity may lead to moderate anti-inflammatory efficacy owing to the dual role of IRAK4 as an active kinase and a scaffolding protein. Herein, we report the design, synthesis, and biological evaluation of an efficient and selective IRAK4 proteolysis-targeting chimeric molecule that eliminates IRAK4 scaffolding functions. The most potent compound, LC-MI-3, effectively degraded cellular IRAK4, with a half-maximal degradation concentration of 47.3 nM. LC-MI-3 effectively inhibited the activation of downstream nuclear factor-κB signaling and exerted more potent pharmacological effects than traditional kinase inhibitors. Furthermore, LC-MI-3 exerted significant therapeutic effects in lipopolysaccharide- and Escherichia coli-induced acute and chronic inflammatory skin models compared with kinase inhibitors in vivo. Therefore, LC-MI-3 is a candidate IRAK4 degrader in alternative targeting strategies and advanced drug development.

Neutrophils in pancreatic ductal adenocarcinoma: bridging preclinical insights to clinical prospects for improved therapeutic strategies.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a dismal five-year survival rate of less than 10%. Neutrophils are key components of the innate immune system, playing a pivotal role in the PDAC immune microenvironment. AREAS COVERED: This review provides a comprehensive survey of the pivotal involvement of neutrophils in the tumorigenesis and progression of PDAC. Furthermore, it synthesizes preclinical and clinical explorations aimed at targeting neutrophils within the milieu of PDAC, subsequently proposing a conceptual framework to propel further inquiry focused on enhancing the therapeutic efficacy of PDAC through neutrophil-targeted strategies. PubMed and Web of Science databases were utilized for researching neutrophils in pancreatic cancer publications prior to 2024. EXPERT OPINION: Neutrophils play roles in promoting tumor growth and metastasis in PDAC and are associated with poor prognosis. However, the heterogeneity and plasticity of neutrophils and their complex relationships with other immune cells and extracellular matrix also provide new insights for immunotherapy targeting neutrophils to achieve a better prognosis for PDAC.

Single-Round Circular Aptamer Discovery Using Bioinspired Magnetosome-Like Magnetic Chain Cross-Linked Graphene Oxide.

Circular aptamers are promising candidates for analytical and therapeutic applications due to their enhanced biological and structural stability. However, the process of circular aptamer selection remains a great challenge, as it requires multiple rounds of binding-separation-amplification that involves issues with nonspecific binding and amplification bias. Here, we develop a highly practical solution for reliable selection of circular aptamers in a single round based on magnetosome-like magnetic chain cross-linked graphene oxide (separation efficiency ≈ 105). High-affinity aptamer candidates can be rapidly selected from a preenriched circular DNA library, while low-affinity candidates are effectively adsorbed and separated by magnetosome-like magnetic chain cross-linked graphene oxide. With lipopolysaccharide as a representative model, the single-round selected lipopolysaccharide circular aptamer has been identified to have a high binding affinity with a Kd value of low to nanomolar range. Using this method, circular aptamers for protein and small-molecule targets were also successfully generated. We envision that this approach will accelerate the discovery of various new circular aptamers and open up a new avenue for analytical and therapeutic studies.

The Impact of Prostate Volume on Prostate Cancer Detection: Comparing Magnetic Resonance Imaging with Transrectal Ultrasound in Biopsy-naïve Men.

Background and objective: This study aimed to determine the difference in prostate volume (PV) derived from transrectal ultrasound (TRUS) and multiparametric magnetic resonance imaging (mpMRI), and to further investigate the role of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD in prostate cancer (PCa) detection in biopsy-naïve men. Methods: Patients who underwent an initial prostate biopsy within 3 mo after mpMRI between January 2016 and December 2021 were analyzed retrospectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of both TRUS-PSAD and mpMRI-PSAD for PCa detection were calculated and compared. The Pearson correlation coefficient, Bland-Altman plot, and receiver operating characteristic curve were also utilized to explore the interests of this study. Key findings and limitations: The median prostate-specific antigen level of 875 patients was 9.79 (interquartile range [IQR]: 7.09-13.50) ng/ml. The median mpMRI-PV and TRUS-PV were 41.92 (IQR: 29.29-60.73) and 41.04 (IQR: 29.24-57.27) ml, respectively, demonstrating a strong linear correlation (r = 0.831, 95% confidence interval: 0.809, 0.850; p < 0.01) and sufficient agreement. No significant difference was observed in terms of the sensitivity, specificity, PPV, and NPV between TRUS-PSAD and mpMRI-PSAD for any PCa and clinically significant PCa (csPCa) detection. The overall discriminative ability of TRUS-PSAD for detecting PCa or non-PCa, as well as csPCa and non-csPCa, was comparable with that of mpMRI-PSAD, and similar results were also observed in the subsequent analysis stratified by mpMRI-PV quartiles, prostate-specific antigen level, and age. The limitations include the retrospective and single-center nature and a lack of follow-up information. Conclusions and clinical implications: TRUS-PV and MRI-PV exhibited a strong linear correlation and reached sufficient agreement. The efficiency of TRUS-PSAD and mpMRI-PSAD for PCa detection was comparable. TRUS could be used for PV estimation and dynamic monitoring of PSAD, and TRUS-PSAD could effectively guide clinical decision-making and optimize diagnostic strategies. Patient summary: In this work, prostate volume (PV) derived from transrectal ultrasound (TRUS) exhibited a strong linear correlation with the PV derived from multiparametric magnetic resonance imaging (mpMRI). The efficiency of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD for the detection of prostate cancer was comparable. TRUS could be used for PV estimation and TRUS-PSAD could help in clinical decision-making and optimizing diagnostic strategies.

Nanoparticles targeting OPN loaded with BY1 inhibits vascular restenosis by inducing FTH1-dependent ferroptosis in vascular smooth muscle cells.

Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.

Highly Sensitive, Low-Energy-Consumption Biomimetic Olfactory Synaptic Transistors Based on the Aggregation of the Semiconductor Films.

Artificial olfactory synaptic devices with low energy consumption and low detection limits are important for the further development of neuromorphic computing and intelligent robotics. In this work, an ultralow energy consumption and low detection limit imitation olfactory synaptic device based on organic field-effect transistors (OFETs) was prepared. The aggregation state of poly(diketopyrrolopyrrole-selenophene) (PTDPP) semiconductor films is modulated by adding unfavorable solvents and annealing treatments to obtain excellent charge transfer and gas synaptic properties. The regulated OFET device can execute basic biological synaptic functions, including excitatory postsynaptic currents (EPSCs), paired-pulse facilitation (PPF), and the transition from short-term to long-term plasticity, at an ultralow operating voltage of -0.0005 V. The ultralow energy consumption during the biomimetic simulation is in the range of 8.94-88 fJ per spike. Noteworthily, the gas detection limit of the device is as low as 50 ppb, well below normal human NO2 gas perception limits (100-1000 ppb). Additionally, high-pass filtering, Pavlovian conditioned reflexes, and decoding of "Morse code" were simulated. Finally, a grid-free conformal device with outstanding flexibility and stability was fabricated. In conclusion, the control of semiconductor thin-film aggregation provides effective guidance for preparing low-energy-consumption, highly sensitive olfactory nerve-mimicking devices and promoting the development of wearable electronics.

An FeCl3-catalyzed three-component reaction for the synthesis of ß-(1,2,3-triazolyl)-ketones using DMF as a one-carbon source.

An FeCl3-catalyzed oxidative condensation of NH-1,2,3-triazoles, aryl methyl ketones (or acetophenones) and DMF (N,N-dimethylformamide) for the synthesis of ß-(1,2,3-triazolyl)-ketones was developed. DMF serves as a one-carbon source, and the resulting products display diverse reaction selectivity, highlighting the existence of distinct approaches.

Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in cocultures demonstrated integrin beta 1 (ITGB1) and vascular endothelial factor A (VEGFA) interactions with neuropilin-1 mediating CAF-epithelial cell cross-talk. Together, this study introduces transfer learning from human single-cell data to organoid coculture analyses for experimental validation of discoveries of cell-cell cross-talk and identifies fibroblast-mediated regulation of EMT and inflammation. SIGNIFICANCE: Adaptation of transfer learning to relate human single-cell RNA sequencing data to organoid-CAF cocultures facilitates discovery of human pancreatic cancer intercellular interactions and uncovers cross-talk between CAFs and tumor cells through VEGFA and ITGB1.

The effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in primary premature ejaculation: a pilot study.

Background: Penile hypersensitivity is not the whole penis, but rather only a part of the penis. Though local anesthetic can prolong intravaginal ejaculation latency time by reducing penile hypersensitivity, the effect on the hypersensitive and nonsensitive areas of penis is still unclear. Aim: The study aimed to explore whether the effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in premature ejaculation. Methods: Penile neurophysiological tests were performed on 290 patients with primary premature ejaculation. The sensory threshold, latency, and amplitude were recorded before and after the topical application of a local anesthetic (lidocaine cream) on the penis. Outcomes: Local anesthetics increased the sensory thresholds of hypersensitive and nonsensitive areas of the penis without difference but only prolonged the latency of the hypersensitive areas. Results: According to the neurophysiological results, 149 of 290 patients with primary premature ejaculation had normal penile sensitivity and 141 had penile hypersensitivity. While penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive, and may be that only a part of the penis is hypersensitive, and we examined the following hypersensitivities: glans hypersensitivity only (14 cases), shaft hypersensitivity only (77 cases), and whole penis hypersensitivity (50 cases). Local anesthetics (lidocaine cream) increased the sensory thresholds of hypersensitive and nonsensitive areas of the penis without difference (P < .001) but only prolonged the latency of the hypersensitive areas (P < .001), and the latency of the nonsensitive areas was not different (P > .05). Clinical Implications: The present discovery implies that it is possible to improve ejaculation by applying local anesthetics externally to the hypersensitive areas of the penis to reduce the afferent local sensory signals, and improve intravaginal ejaculation latency time through accurately decreasing penile sensibility. Strengths & Limitations: This is the first large-sample study to explore the difference of local anesthetics' effects on the hypersensitive and nonsensitive areas of the penis by means of neurophysiological methods in premature ejaculation. Our study exclusively examines alterations in penile evoked potential following electrical stimulation, which may not entirely encompass shifts in penile receptivity during sexual activity. Conclusion: The effects of local anesthetics on the same penis varied with penile sensitivity, and can only prolong the latency of hypersensitive area of the penis. The effect of local anesthetic on the hypersensitive and nonsensitive areas of the penis is different in premature ejaculation.

Discovery of PXR agonists from Hypericum japonicum: A class of novel nonaromatic acylphloroglucinol-terpenoid adducts.

Pregnane X receptor (PXR) has been considered as a promising therapeutic target for cholestasis due to its crucial regulation in bile acid biosynthesis and metabolism. To search promising natural PXR agonists, the PXR agonistic activities of five traditional Chinese medicines (TCMs) with hepatoprotective efficacy were assayed, and Hypericum japonicum as the most active one was selected for subsequent phytochemical investigation, which led to the isolation of eight nonaromatic acylphloroglucinol-terpenoid adducts including seven new compounds (1 - 4, 5a, 5b and 6). Their structures including absolute configurations were determined by comprehensive spectroscopic, computational and X-ray diffraction analysis. Meanwhile, the PXR agonistic activities of aplenty compounds were evaluated via dual-luciferase reporter assay, RT-qPCR and immunofluorescence. Among them, compounds 1 - 4 showed more potent activity than the positive drug rifampicin. Furthermore, the molecular docking revealed that 1 - 4 were docked well on the PXR ligand binding domain and formed hydrogen bonds with amino acid residues Gln285, Ser247 and His409. This investigation revealed that H. japonicum may serve as a rich source of natural PXR agonists.

The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia.

With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune microenvironment may help identify potential therapeutic targets for cancer cachexia. Herein, we investigate the critical role of macrophages in potentiating pancreatic cancer induced muscle wasting via promoting TWEAK (TNF-like weak inducer of apoptosis) secretion from the tumor. Specifically, depletion of macrophages reverses muscle degradation induced by tumor cells. Macrophages induce non-autonomous secretion of TWEAK through CCL5/TRAF6/NF-κB pathway. TWEAK promotes muscle atrophy by activating MuRF1 initiated muscle remodeling. Notably, tumor cells recruit and reprogram macrophages via the CCL2/CCR2 axis and disrupting the interplay between macrophages and tumor cells attenuates muscle wasting. Collectively, this study identifies a feedforward loop between pancreatic cancer cells and macrophages, underlying the non-autonomous activation of TWEAK secretion from tumor cells thereby providing promising therapeutic targets for pancreatic cancer cachexia.

Effect of "Tiaoshen" acupuncture technique on mild depression and its underlying mechanism: A randomized controlled trial study protocol.

Background: Mild depression is not just a mental disease, but also a serious and long-term public health issue. It affects the quality of life of patients and can quickly develop into major depression. There are currently no effective drug treatments with high efficacy and few adverse reactions. Acupuncture may be an alternative treatment option. Preliminary experiments and practices have demonstrated that "Tiaoshen" acupuncture improves symptoms in patients who have depression, however the underlying data and method remain unclear at present. Methods: This is a prospective, single-center, single-blind, randomized controlled trial. We plan to recruit 70 participants and randomly assign them to receive "Tiaoshen" acupuncture or traditional acupuncture at a ratio of 1:1. Then, all the participants will receive the appropriate acupuncture treatment for four weeks. The results of the Hamilton Depression Rating Scale (HDSR-24) will serve as the primary outcome, while the results of the Patient Health Questionnaire-9 (PHQ-9) and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) will serve as secondary outcomes. Evaluations will be conducted at baseline, 1, 2, and 4 weeks after treatment initiation, and 1 and 3 months after treatment completion. The safety of the intervention will be evaluated every week using the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Treatment Emergent Symptoms Scale (TESS). Serum levels of oxidative stress markers 8-iso-prostaglandin F2α (8-iso-PGF2α), superoxide dismutase (SOD), uric acid (UA), and total bilirubin (TBIL) will be measured at baseline and the end of the treatment. We will conduct a statistical analysis of intention to treat (ITT) and conformance to protocol set (PPS) data. Discussion: This research aims to provide high-quality evidence for the efficacy and safety of "Tiaoshen" acupuncture as a treatment for mild depression. In addition, the mechanism through which acupuncture heals mild depression will be investigated.

Soybean steroids improve crop abiotic stress tolerance and increase yield.

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.

Differences between the glans and shaft of the penis: a review.

INTRODUCTION: The penis serves as a vital receptor in men, playing a significant role in sexual intercourse. While there are discernible disparities between the glans penis and the penile shaft, a comprehensive and detailed analysis of these distinctions is currently lacking. OBJECTIVES: This study aimed to review the existing literature on the variances between the glans penis and the penile shaft, providing a systematic examination of their anatomical and histological dissimilarities. METHODS: Our investigation encompassed a thorough search of the published literature, including original articles, reviews, letters to the editor, and case reports focused on the penis. We conducted a comprehensive review of the anatomical and histological dissimilarities between the glans penis and the penile shaft. RESULTS: The following key differences were identified. First, regarding innervation, the glans penis and the penile shaft possess distinct neural pathways. The glans penis exhibits a 3-dimensional structure, while the penile shaft exhibits a 2-dimensional distribution. Notably, the nerves of the penile shaft extend penetrating branches into the corpus cavernosum. Furthermore, there are variations in nerve-specific antibodies between the 2 regions. Second, regarding composition, the glans penis and the penile shaft consist of dissimilar cavernous bodies. The glans penis contains unique epithelial structures and receptors, setting it apart from the penile shaft. Third, regarding the veins, there are disparities in the venous systems of the glans penis and the penile shaft. Fourth, regarding biothesiometry, variances in biothesiometry research have been observed between the 2 regions. CONCLUSION: There are differences between the glans and the shaft. To further advance our understanding, future research should delve deeper into the discrepancies between the glans penis and the penile shaft. Additionally, a more specialized subdivision of the glans penis and the penile shaft would facilitate more precise and tailored treatments.

Synthetic biology-based bacterial extracellular vesicles displaying BMP-2 and CXCR4 to ameliorate osteoporosis.

Osteoporosis (OP) is a systematic bone disease characterized by low bone mass and fragile bone microarchitecture. Conventional treatment for OP has limited efficacy and long-term toxicity. Synthetic biology makes bacterial extracellular vesicle (BEVs)-based therapeutic strategies a promising alternative for the treatment of OP. Here, we constructed a recombinant probiotics Escherichia coli Nissle 1917-pET28a-ClyA-BMP-2-CXCR4 (ECN-pClyA-BMP-2-CXCR4), in which BMP-2 and CXCR4 were overexpressed in fusion with BEVs surface protein ClyA. Subsequently, we isolated engineered BEVs-BMP-2-CXCR4 (BEVs-BC) for OP therapy. The engineered BEVs-BC exhibited great bone targeting in vivo. In addition, BEVs-BC had good biocompatibility and remarkable ability to promote osteogenic differentiation of BMSCs. Finally, the synthetic biology-based BEVs-BC significantly prevented the OP in an ovariectomized (OVX) mouse model. In conclusion, we constructed BEVs-BC with both bone-targeting and bone-forming in one-step using synthetic biology, which provides an effective strategy for OP and has great potential for industrialization.