The role of adjuvant chemotherapy after radical surgery in patients with lymph node-positive bladder cancer or locally advanced (pT3, pT4a) bladder cancer: A meta-analysis and systematic review.

PURPOSE: This study aims to evaluate the impact of adjuvant chemotherapy (AC) on survival outcomes in patients with lymph node-positive bladder cancer or locally advanced (pT3, pT4a) bladder cancer after surgery. We also seek to identify which patients with pN+ bladder cancer are most likely to benefit from AC after radical cystectomy (RC). METHODS: We searched databases including Embase, PubMed, Cochrane, and ClinicalTrials.gov to identify relevant literature published in English up to February 2024. We used Stata to compare various parameters. The study has been registered in PROSPERO. RESULTS: A total of 21 studies were analyzed, including 1 randomized controlled trial, 6 prospective studies, and 14 retrospective studies, encompassing 12,888 patients. The meta-analysis showed that for patients with lymph node-positive bladder cancer, the adjuvant chemotherapy (AC) group had higher overall survival (OS) (I2=58.2%, HR 0.69; 95% CI: 0.57-0.83; P=0.019) and recurrence-free survival (RFS) (I2=66.6%, HR 0.71; 95% CI: 0.57-0.89; P=0.006) compared to the radical cystectomy (RC) group. For patients with pT3 and pT4a bladder cancer, the AC group had higher overall survival (OS) (I2=57.3%, HR 0.77; 95% CI: 0.67-0.89; P=0.022) and cancer-specific survival (CSS) (I2=47.2%, HR 0.75; 95% CI: 0.64-0.88; P=0.0048) compared to the RC group. At the same time, according to the different chemotherapy regimens, we divided the cisplatin-based chemotherapy regimen and carboplatin based chemotherapy or other regimens into two subgroups for analysis, and found that the OS (I2=41.4%, HR 0.64; 95%CI: 0.51~0.80; P=0.000) was better than carboplatin and other chemotherapy regimens (I2=64.1%, HR 0.77; 95%CI: 069~0.86; P=0.000); Lymph node density (LND) was found to be an independent predictor of overall survival (HR=1.6; 95% CI: 1.31-1.95; P=0.0000). CONCLUSION: This study found that postoperative adjuvant chemotherapy (AC) improves overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) in patients with pT3, pT4a, It was also confirmed that cisplatin-based chemotherapy regimen was more beneficial for patients with bladder cancer; and lymph node-positive bladder cancer. Additionally, our analysis revealed that patients with lymph node-positive bladder cancer benefit more from postoperative AC. It was further demonstrated that cisplatin-based chemotherapy regimens are more beneficial than other regimens for patients with locally advanced bladder cancer.

Imaging tunable Luttinger liquid systems in van der Waals heterostructures.

One-dimensional (1D) interacting electrons are often described as a Luttinger liquid1-4 having properties that are intrinsically different from those of Fermi liquids in higher dimensions5,6. In materials systems, 1D electrons exhibit exotic quantum phenomena that can be tuned by both intra- and inter-1D-chain electronic interactions, but their experimental characterization can be challenging. Here we demonstrate that layer-stacking domain walls (DWs) in van der Waals heterostructures form a broadly tunable Luttinger liquid system, including both isolated and coupled arrays. We have imaged the evolution of DW Luttinger liquids under different interaction regimes tuned by electron density using scanning tunnelling microscopy. Single DWs at low carrier density are highly susceptible to Wigner crystallization consistent with a spin-incoherent Luttinger liquid, whereas at intermediate densities dimerized Wigner crystals form because of an enhanced magneto-elastic coupling. Periodic arrays of DWs exhibit an interplay between intra- and inter-chain interactions that gives rise to new quantum phases. At low electron densities, inter-chain interactions are dominant and induce a 2D electron crystal composed of phased-locked 1D Wigner crystal in a staggered configuration. Increased electron density causes intra-chain fluctuation potentials to dominate, leading to an electronic smectic liquid crystal phase in which electrons are ordered with algebraical correlation decay along the chain direction but disordered between chains. Our work shows that layer-stacking DWs in 2D heterostructures provides opportunities to explore Luttinger liquid physics.

Efficacy and safety of platelet-rich plasma (PRP) in erectile dysfunction (ED): a systematic review and meta-analysis.

Background: Erectile dysfunction (ED) is a prevalent condition in aging men. Meanwhile, platelet-rich plasma (PRP), an emerging treatment alternative, has demonstrated potential in mitigating symptoms associated with ED. Our research aimed to explore the safety and effectiveness of employing PRP as a treatment strategy for ED. Methods: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols, our research involved a thorough search across multiple databases: PubMed, Web of Science, Embase, and the Cochrane Controlled Trials Register. To assess the methodological rigor of the studies selected, we applied the modified Jadad scale and the Methodological Index for Non-Randomized Studies (MINORS) scale as evaluation tools. Subsequent to these evaluations, data analysis was conducted. Results: Our analysis included seven non-randomized studies and three randomized controlled trials (RCTs). These studies showed that the International Index of Erectile Function-Erectile Function (IIEF-EF) scores improved significantly after 1, 3, and 6 months of PRP treatment, with increases of 4.05 [95% confidence interval (CI): 2.42, 5.68; P<0.001], 3.73 (95% CI: 2.93, 4.53; P<0.001), and 3.92 (95% CI: 3.00, 4.85; P<0.001) respectively, compared to the baseline scores. Additionally, compared to the placebo group, the PRP group showed significantly higher IIEF-EF scores. PRP treatment also had a beneficial impact on minimal clinically important difference (MCID) and peak systolic velocity (PSV). However, no significant differences were found between the PRP and placebo groups in terms of erectile hardness score (EHS) [mean difference (MD) =0.63; 95% CI: 0.26, 0.99; P<0.001] or visual analog scale (VAS) pain scores (MD =0.24; 95% CI: -0.05, 0.54; P=0.11). Conclusions: Our study results demonstrated significant efficacy and safety of PRP in treating ED. Due to the fact that most of the literature we included was single-arm studies, it was imperative for future research to provide higher-quality evidence for validation.

Wigner molecular crystals from multielectron moiré artificial atoms.

Semiconductor moiré superlattices provide a versatile platform to engineer quantum solids composed of artificial atoms on moiré sites. Previous studies have mostly focused on the simplest correlated quantum solid-the Fermi-Hubbard model-in which intra-atom interactions are simplified to a single onsite repulsion energy U. Here we report the experimental observation of Wigner molecular crystals emerging from multielectron artificial atoms in twisted bilayer tungsten disulfide moiré superlattices. Using scanning tunneling microscopy, we demonstrate that Wigner molecules appear in multielectron artificial atoms when Coulomb interactions dominate. The array of Wigner molecules observed in a moiré superlattice comprises a crystalline phase of electrons: the Wigner molecular crystal, which is shown to be highly tunable through mechanical strain, moiré period, and carrier charge type.

Exploring Dimethylsulfoniopropionate as a potential treatment for Alzheimer's disease: A study using the 3 × Tg-AD mouse model.

BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, affects a broad spectrum of aging populations. AD is characterized by pathological amyloid-ß (Aß) plaques and neurofibrillary tangles, leading to neural degeneration and cognitive decline. The lack of effective treatments for AD highlights the urgent need for novel therapeutic agents, particularly in the early stages. Dimethylsulfoniopropionate (DMSP) is a natural marine compound with antioxidant and neuroprotective properties. However, studies on the efficacy of DMSP in the treatment of AD and its associated mechanisms are limited. PURPOSE: This study aimed to explore the therapeutic effects and mechanisms of action of DMSP as an AD treatment using a preclinical 3 × Tg-AD mouse model. METHODS: The research involved administering DMSP (7 µg/mL and 11 µg/mL in drinking water) to four-month-old 3 × Tg-AD mice consecutively for three months. The Y-maze test, novel object recognition test, and Morris water maze test were used to assess memory and learning ability. The relative expression levels and distribution of proteins relevant to Aß and tau pathology, synapses, and glial cells were analyzed using western blotting and immunofluorescence assays. Additionally, proteomic and bioinformatics approaches were used to explore the potential targets of DMSP treatment. RESULTS: DMSP-treated AD mice showed significantly enhanced cognitive function, suggesting that DMSP mitigates memory and learning impairments in AD. Moreover, DMSP diminished the abnormal accumulation of Aß and phosphorylated tau in both the cortex and hippocampus, which are crucial hallmarks of AD pathology. In addition to its neuroprotective properties, DMSP restored synaptic density and the expression of synaptic and neuronal proteins, which are essential for proper brain function. DMSP displayed anti-inflammatory properties, as evidenced by its ability to suppress inflammatory astrocytes and maintain microglial homeostasis. Notably, DMSP facilitated the maturation of oligodendrocytes (OLs) from oligodendrocyte progenitor cells (OPCs), a critical process in the development of the brain myelination architecture. Proteomic analysis revealed that DMSP positively influenced biological processes crucial for oligodendrocyte development, myelination, and axonal ensheathment, which are often compromised in patients with AD. Protein validation and brain tissue staining supported the role of DMSP in preserving myelin enrichment and sheath integrity. These therapeutic effects were largely attributed to the enhanced expression of myelin-associated glycoprotein (Mag) and tetraspanin Cd9. CONCLUSION: Overall, our findings highlight DMSP as a promising novel therapeutic candidate for AD, offering multifaceted benefits in cognitive and memory enhancement, reduction of Aß and tau pathology, neuronal synapse protection, anti-inflammatory effects, and myelin sheath restoration as an innovative target compared to other studies. In addition to being a potentially effective treatment for AD, DMSP may also have the potential to address other neurodegenerative diseases that are closely associated with myelin impairment.

BOLERO-5: a phase II study of everolimus and exemestane combination in Chinese post-menopausal women with ER + /HER2- advanced breast cancer.

BACKGROUND: The global BOLERO-2 trial established the efficacy and safety of combination everolimus (EVE) and exemestane (EXE) in the treatment of estrogen receptor positive (ER +), HER2-, advanced breast cancer (ABC). BOLERO-5 investigated this combination in a Chinese population (NCT03312738). METHODS: BOLERO-5 is a randomized, double-blind, multicenter, placebo controlled, phase II trial comparing EVE (10 mg/day) or placebo (PBO) in combination with EXE (25 mg/day). The primary endpoint was progression-free survival (PFS) per investigator assessment. Secondary endpoints included PFS per blinded independent review committee (BIRC), overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), pharmacokinetics, and safety. RESULTS: A total of 159 patients were randomized to EVE + EXE (n = 80) or PBO + EXE (n = 79). By investigator assessment, treatment with EVE + EXE prolonged median PFS by 5.4 months (HR 0.52; 90% CI 0.38, 0.71), from 2.0 months (PBO + EXE; 90% CI 1.9, 3.6) to 7.4 months (EVE + EXE; 90% CI 5.5, 9.0). Similar results were observed following assessment by BIRC, with median PFS prolonged by 4.3 months. Treatment with EVE + EXE was also associated with improvements in ORR and CBR. No new safety signals were identified in BOLERO-5, with the incidence of adverse events in Chinese patients consistent with the safety profile of both drugs. CONCLUSION: The efficacy and safety results of BOLERO-5 validate the findings from BOLERO-2, and further support the use of EVE + EXE in Chinese post-menopausal women with ER + , HER2- ABC. NCT03312738, registered 18 October 2017.

A systematic review and meta-analysis of the role of perineal hydrodissection in perioperative, oncologic, and functional outcomes for patients undergoing robot-assisted radical prostatectomy.

This study aims to compare the perioperative, oncological, and functional outcomes of perineal hydrodissection (HD) with standard treatment (ST) in patients undergoing robot-assisted radical prostatectomy. We performed an exhaustive search in databases such as PubMed, Embase, Web of Science, and the Cochrane Library, seeking English-language studies relevant to our research question, with a cutoff date of April 2024. The pooled results were assessed using the weighted mean differences (WMDs), standardized mean differences (SMDs), and odds ratios (ORs) metrics. We also performed a sensitivity analysis. The meta-analysis was conducted utilizing Stata/MP version 18 software. The study was registered with PROSPERO (ID: CRD 42024536400). We included a total of five studies (three RCTs and two retrospective studies). According to the data from the Meta-analysis, the HD group showed positive effects in promoting urinary continence (OR 2.64, 95% CI 1.36, 5.12; p = 0.004 < 0.05) and erectile function (SMD 0.92, 95%CI 0.56, 1.27; p < 0.05) within 3 months after surgery. However, no notable disparities were observed in terms of operative time, estimated blood loss, bilateral nerve-sparing rate, or the rate of positive surgical margin. Perineal hydrodissection can be safely applied in robot-assisted radical prostatectomy (RARP), offering a distinct advantage in functional outcomes compared to those who undergo standard robot-assisted prostatectomy alone.

Chern Insulator States with Tunable Chern Numbers in a Graphene Moiré Superlattice.

Moiré superlattices, constituted by two-dimensional materials, demonstrate a variety of strongly correlated and topological phenomena including correlated insulators, superconductivity, and integer/fractional Chern insulators. In the realm of topological nontrivial Chern insulators within specific moiré superlattices, previous studies usually observe a single Chern number at a given filling factor in a device. Here we present the observation of gate-tunable Chern numbers within the Chern insulator state of an ABC-stacked trilayer graphene/hexagonal boron nitride moiré superlattice device. Near quarter filling, the moiré superlattice exhibits spontaneous valley polarization and distinct ferromagnetism associated with the Chern insulator states over a range of the displacement field. Surprisingly we find a transition of the Chern number from C = 3 to 4 as the displacement field is increased. Our observation of gate-tunable correlated Chern insulators suggests new ways to control and manipulate topological states in a moiré superlattice device.

Comparative analysis of perioperative outcomes in obese patients undergoing robot-assisted radical prostatectomy (RARP) versus open radical prostatectomy (ORP): a systematic review and meta-analysis.

The purpose of this study was to conduct a comparative analysis of the perioperative outcomes associated with robot-assisted laparoscopic prostatectomy (RARP) versus open radical prostatectomy (ORP) in the obese population diagnosed with prostate cancer. We performed a comprehensive search in key databases such as PubMed, Embase, Web of Science, and the Cochrane Library, encompassing studies of all languages, with a final search date of April 2024. We also omitted articles that consisted of conference abstracts and content that was not pertinent to our study. The aggregated outcomes were evaluated utilizing the metrics of weighted mean differences (WMDs) and odds ratios (ORs). A sensitivity analysis was also integrated into our assessment. The meta-analysis was facilitated by employing Stata/MP version 18 software. Additionally, the study was duly registered with PROSPERO under the identifier: CRD 42024540216. This meta-analysis, which included five trials, shows that compared to ORP, RARP is associated with a reduced estimated blood loss (EBL) (WMD -445.77, 95%CI -866.08, -25.45; p = 0.038), a decreased transfusion rate (OR 0.17, 95%CI 0.13, 0.21; p < 0.001), and a diminished overall complication rate (OR 0.71, 95%CI 0.58, 0.86; p = 0.001). No statistically significant differences were found in operative time (OT) (WMD 1.88, 95%CI -46.53, 50.28; p = 0.939) or length of stay (LOS) (WMD -0.41, 95%CI -1.07, 0.25; p = 0.221). Among patients with obesity and prostate cancer, RARP demonstrates advantages over ORP by reducing estimated blood loss, transfusion requirements, and the incidence of complications. Notably, there were no significant differences in operative duration and hospital stay between the two surgical approaches. These findings suggest that RARP could be a preferable surgical option for obese individuals with prostate cancer.

MTCSNet: One-stage learning and two-point labeling are sufficient for cell segmentation.

Deep convolution neural networks have been widely used in medical image analysis, such as lesion identification in whole-slide images, cancer detection, and cell segmentation, etc. However, it is often inevitable that researchers try their best to refine annotations so as to enhance the model performance, especially for cell segmentation task. Weakly supervised learning can greatly reduce the workload of annotations, while there is still a huge performance gap between the weakly and fully supervised learning approaches. In this work, we propose a weakly-supervised cell segmentation method, namely Multi-Task Cell Segmentation Network (MTCSNet), for multi-modal medical images, including pathological, brightfield, fluorescent, phase-contrast and differential interference contrast images. MTCSNet is learnt in a single-stage training manner, where only two annotated points for each cell provide supervision information, and the first one is the centroid, the second one is its boundary. Additionally, five auxiliary tasks are elaborately designed to train the network, including two pixel-level classifications, a pixel-level regression, a local temperature scaling and an instance-level distance regression task, which is proposed to regress the distances between the cell centroid and its boundaries in eight orientations. The experimental results indicate that our method outperforms all state-of-the-art weakly-supervised cell segmentation approaches on public multi-modal medical image datasets. The promising performance also shows that a single-stage learning with two-point labeling approach are sufficient for cell segmentation, instead of fine contour delineation. The codes are available at: https://github.com/binging512/MTCSNet.

Iron ions-sequestrable and antioxidative carbon dot-based nano-formulation with nitric oxide release for Parkinson's disease treatment.

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp2-hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD.

Comparison of laser versus cold knife visual internal urethrotomy in the treatment of urethral stricture (stricture length <2 cm): A systematic review and meta-analysis.

PURPOSE: There is still controversy regarding the safety and efficacy of cold knife visual internal urethrotomy and laser incisions for the treatment of urethral stricture. This study aims to compare the results of postoperative long-term and short-term maximum urinary flow rates (Qmax), surgical time, postoperative complications, and 1-year recurrence rates between the cold knife and laser surgery. METHODS: We searched databases including Embase, PubMed, Cochrane, and Clinical Trials.gov to identify relevant literature published in English up to September 2023. We used Stata to compare various parameters. This study is registered in PROSPERO (CRD42023471634). Nine comparative experiments were conducted, involving a total of 659 participants. RESULTS: The laser group showed significantly better results compared to the cold knife group in terms of postoperative 12-month maximum urinary flow rate (mean differences [MD] 2.131; 95% [1.015, 3.249], P < .0001), postoperative bleeding (RR 0.277, 95% [0.079, 0.977], P = .046), and 1-year recurrence rate (RR 0.667, 95% [0.456, 0.976], P = .037). However, there were no significant differences in postoperative 6-month and 3-month Qmax, surgical time, urethral leakage complications, overall complications, and Visual Analog Scale (VAS) scores. CONCLUSION: The current study results suggest that laser urethral incision has greater advantages in the long-term (12 months), 1-year recurrence rate, and bleeding complications compared to cold knife urethral incision in the treatment of urethral stricture (<2 cm). Therefore, laser urethral incision may be a better choice for patients with urethral stricture.

Effects of natural extract interventions in prostate cancer: A systematic review and network meta-analysis.

BACKGROUND: Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. OBJECTIVE: Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. METHODS: Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. RESULTS: Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. CONCLUSION: The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.

28.02 W LD side-pumped CW laser operated at 2.8†µm in YSGG/Er:YSGG/YSGG crystal.

We demonstrated a 978 nm laser diode (LD) side-pumped YSGG/Er:YSGG/YSGG composite crystal with a size of Ф 3 mm × 65 mm and continuous-wave (CW) mode. By optimizing resonator length and output mirror transmittance, a maximum output power of 28.02 W is generated, corresponding to slope efficiency of 17.55% and optical-optical efficiency of 12.29%, respectively. The thermal focal lengths are obtained by resonator stability condition. The laser wavelength is centered near 2.8 µm. Moreover, the beam quality factors M x2/M y2 are fitted to be 8.14 and 7.35, respectively. The above results indicate that a high-performance 2.8 µm CW laser can be achieved by LD side-pumped YSGG/Er:YSGG/YSGG composite crystal with excellent heat dissipation ability, which promotes effectively the development and applications of the mid-infrared solid-state lasers.

Discovery of YFJ-36: Design, Synthesis, and Antibacterial Activities of Catechol-Conjugated ß-Lactams against Gram-Negative Bacteria.

Cefiderocol is the first approved catechol-conjugated cephalosporin against multidrug-resistant Gram-negative bacteria, while its application was limited by poor chemical stability associated with the pyrrolidinium linker, moderate potency against Klebsiella pneumoniae and Acinetobacter baumannii, intricate procedures for salt preparation, and potential hypersensitivity. To address these issues, a series of novel catechol-conjugated derivatives were designed, synthesized, and evaluated. Extensive structure-activity relationships and structure-metabolism relationships (SMR) were conducted, leading to the discovery of a promising compound 86b (Code no. YFJ-36) with a new thioether linker. 86b exhibited superior and broad-spectrum in vitro antibacterial activity, especially against A. baumannii and K. pneumoniae, compared with cefiderocol. Potent in vivo efficacy was observed in a murine systemic infection model. Furthermore, the physicochemical stability of 86b in fluid medium at pH 6-8 was enhanced. 86b also reduced potential the risk of allergy owing to the quaternary ammonium linker. The improved properties of 86b supported its further research and development.

Design, Synthesis, and Biological Evaluation of Novel Arylomycins against Multidrug-Resistant Gram-Negative Bacteria.

G0775, an arylomycin-type SPase I inhibitor that is being evaluated in a preclinical study, exhibited potent antibacterial activities against some Gram-negative bacteria but meanwhile suffered defects such as a narrow antibacterial spectrum and poor pharmacokinetic properties. Herein, systematic structural modifications were carried out, including optimization of the macrocyclic skeleton, warheads, and lipophilic regions. The optimization culminated in the discovery of 138f, which showed more potent activity and a broader spectrum against clinically isolated carbapenem-resistant Gram-negative bacteria, especially against Acinetobacter baumannii and Pseudomonas aeruginosa. 162, the free amine of 138f, exhibited an excellent pharmacokinetic profile in rats. In a neutropenic mouse thigh model of infection with multidrug-resistant P. aeruginosa, the potent in vivo antibacterial efficacy of 162 was confirmed and superior to that of G0775 (3.5-log decrease vs 1.1-log decrease in colony-forming unit (CFU)). These results support 162 as a potential antimicrobial agent for further research.

Water Impalement Resistance and Drag Reduction of the Superhydrophobic Surface with Hydrophilic Strips.

Superhydrophobic surfaces (SHS) offer versatile applications by trapping an air layer within microstructures, while water jet impact can destabilize this air layer and deactivate the functions of the SHS. The current work presents for the first time that introducing parallel hydrophilic strips to SHS (SHS-s) can simultaneously improve both water impalement resistance and drag reduction (DR). Compared with SHS, SHS-s demonstrates a 125% increase in the enduring time against the impact of water jet with velocity of 11.9 m/s and a 97% improvement in DR at a Reynolds number of 1.4 × 104. The key mechanism lies in the enhanced stability of the air layer due to air confinement by the adjacent three-phase contact lines. These lines not only impede air drainage through the surface microstructures during water jet impact, entrapping the air layer to resist water impalement, but also prevent air floating up due to buoyancy in Taylor-Couette flow, ensuring an even spread of the air layer all over the rotor, boosting DR. Moreover, failure modes of SHS under water jet impact are revealed to be related to air layer decay and surface structure destruction. This mass-producible structured surface holds the potential for widespread use in DR for hulls, autonomous underwater vehicles, and submarines.

Enhancing healthy aging with small molecules: A mitochondrial perspective.

The pursuit of enhanced health during aging has prompted the exploration of various strategies focused on reducing the decline associated with the aging process. A key area of this exploration is the management of mitochondrial dysfunction, a notable characteristic of aging. This review sheds light on the crucial role that small molecules play in augmenting healthy aging, particularly through influencing mitochondrial functions. Mitochondrial oxidative damage, a significant aspect of aging, can potentially be lessened through interventions such as coenzyme Q10, alpha-lipoic acid, and a variety of antioxidants. Additionally, this review discusses approaches for enhancing mitochondrial proteostasis, emphasizing the importance of mitochondrial unfolded protein response inducers like doxycycline, and agents that affect mitophagy, such as urolithin A, spermidine, trehalose, and taurine, which are vital for sustaining protein quality control. Of equal importance are methods for modulating mitochondrial energy production, which involve nicotinamide adenine dinucleotide boosters, adenosine 5'-monophosphate-activated protein kinase activators, and compounds like metformin and mitochondria-targeted tamoxifen that enhance metabolic function. Furthermore, the review delves into emerging strategies that encourage mitochondrial biogenesis. Together, these interventions present a promising avenue for addressing age-related mitochondrial degradation, thereby setting the stage for the development of innovative treatment approaches to meet this extensive challenge.

Gut microbiota in patients with prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence indicates that gut microbiota are closely related to prostate cancer. This study aims to assess the gut microbiota composition in patients with prostate cancer compared to healthy participants, thereby advancing understanding of gut microbiota's role in prostate cancer. METHODS: A systematic search was conducted across PubMed, Web of Science, and Embase databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS), and pertinent data were analyzed. The kappa score assessed interrater agreement. RESULTS: This study encompassed seven research papers, involving 250 prostate cancer patients and 192 controls. The kappa was 0.93. Meta-analysis results showed that alpha-diversity of gut microbiota in prostate cancer patients was significantly lower than in the control group. In terms of gut microbiota abundance, the ratio of Proteobacteria, Bacteroidia, Clostridia, Bacteroidales, Clostridiales, Prevotellaceae, Lachnospiraceae, Prevotella, Escherichia-Shigella, Faecalibacterium, and Bacteroides was higher in prostate cancer patients. Conversely, the abundance ratio of Actinobacteria, Bacteroidetes, Firmicutes, Selenomonadales, Veillonella, and Megasphaera was higher in the control group. CONCLUSION: Our study reveals differences in alpha-diversity and abundance of gut microbiota between patients with prostate cancer and controls, indicating gut microbiota dysbiosis in those with prostate cancer. However, given the limited quality and quantity of selected studies, further research is necessary to validate these findings.

Microglia in neuroimmunopharmacology and drug addiction.

Drug addiction is a chronic and debilitating disease that is considered a global health problem. Various cell types in the brain are involved in the progression of drug addiction. Recently, the xenobiotic hypothesis has been proposed, which frames substances of abuse as exogenous molecules that are responded to by the immune system as foreign "invaders", thus triggering protective inflammatory responses. An emerging body of literature reveals that microglia, the primary resident immune cells in the brain, play an important role in the progression of addiction. Repeated cycles of drug administration cause a progressive, persistent induction of neuroinflammation by releasing microglial proinflammatory cytokines and their metabolic products. This contributes to drug addiction via modulation of neuronal function. In this review, we focus on the role of microglia in the etiology of drug addiction. Then, we discuss the dynamic states of microglia and the correlative and causal evidence linking microglia to drug addiction. Finally, possible mechanisms of how microglia sense drug-related stimuli and modulate the addiction state and how microglia-targeted anti-inflammation therapies affect addiction are reviewed. Understanding the role of microglia in drug addiction may help develop new treatment strategies to fight this devastating societal challenge.