Ancient Mitogenomes Reveal the Maternal Genetic History of East Asian Dogs.

Recent studies have suggested that dogs were domesticated during the Last Glacial Maximum (LGM) in Siberia, which contrasts with previous proposed domestication centers (e.g. Europe, the Middle East, and East Asia). Ancient DNA provides a powerful resource for the study of mammalian evolution and has been widely used to understand the genetic history of domestic animals. To understand the maternal genetic history of East Asian dogs, we have made a complete mitogenome dataset of 120 East Asian canids from 38 archaeological sites, including 102 newly sequenced from 12.9 to 1 ka BP (1,000 years before present). The majority (112/119, 94.12%) belonged to haplogroup A, and half of these (55/112, 49.11%) belonged to sub-haplogroup A1b. Most existing mitochondrial haplogroups were present in ancient East Asian dogs. However, mitochondrial lineages in ancient northern dogs (northeastern Eurasia and northern East Asia) were deeper and older than those in southern East Asian dogs. Results suggests that East Asian dogs originated from northeastern Eurasian populations after the LGM, dispersing in two possible directions after domestication. Western Eurasian (Europe and the Middle East) dog maternal ancestries genetically influenced East Asian dogs from approximately 4 ka BP, dramatically increasing after 3 ka BP, and afterwards largely replaced most primary maternal lineages in northern East Asia. Additionally, at least three major mitogenome sub-haplogroups of haplogroup A (A1a, A1b, and A3) reveal at least two major dispersal waves onto the Qinghai-Tibet Plateau in ancient times, indicating eastern (A1b and A3) and western (A1a) Eurasian origins.

Zeolitic Pickering Emulsifier with Intrinsic Amphiphilicity.

The formation of oil-in-water Pickering emulsions stabilized by lamellar zeolite MWW (International Zeolite Association, three-letters code) emulsifier without surface grafting is investigated. The crucial emulsification factors are the oligolayer morphology and amphiphilicity developed upon acidic treatment (NH4+ exchange/calcination, HNO3 treatment). In contrast with the readily available/abundant hydrophilic ≡Si-OH group in layer MWW, the lipophilicity generated by strong acid sites is another key to the success of emulsification. Hydrocarbon-strong acid site interaction is long known in petrochemistry and superacid research. However, to the best of our knowledge, this interaction was first introduced to gain lipophilicity in emulsion formation. Finally, the Pd-loaded acidic form of the MWW zeolite successfully stabilized the toluene/H2O emulsion system. The biphasic interfacial nitroarene hydrogenation demonstrated excellent catalytic performance. Overall, this work provided not only a new kind of intrinsic solid to emulsify the organic-aqueous biphase system but also a new mechanism to generate lipophilicity. Both are important for the applications and designs of Pickering emulsion materials.

Comparing Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prediction of Extraprostatic Extension of Prostate Cancer and Surgical Guidance: A Prospective Nonrandomized Clinical Trial.

PURPOSE: Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if 68Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach. MATERIALS AND METHODS: We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy. After mpMRI and PSMA-PET images were read for EPE prediction, surgeons prospectively answered questionnaires based on mpMRI and PSMA-PET scans on the decision for nerve-sparing or nonnerve-sparing approach. Final whole-mount pathology was the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curves were calculated and McNemar's test was used to compare imaging modalities. RESULTS: The median age and PSA were 61.5 years and 7.0 ng/dL. The sensitivity for EPE along the posterior neurovascular bundle was higher for PSMA-PET than mpMRI (86% vs 57%, P = .03). For MRI, the specificity, positive predictive value, negative predictive value, and area under the curve for the receiver operating characteristic curves were 77%, 40%, 87%, and 0.67, and for PSMA-PET were 73%, 46%, 95%, and 0.80. PSMA-PET and mpMRI reads differed on 27 nerve bundles, with PSMA-PET being correct in 20 cases and MRI being correct in 7 cases. Surgeons predicted correct nerve-sparing approach 74% of the time with PSMA-PET scan in addition to mpMRI compared to 65% with mpMRI alone (P = .01). CONCLUSIONS: PSMA-PET scan was more sensitive than mpMRI for EPE along the neurovascular bundles and improved surgical decisions for nerve-sparing approach. Further study of PSMA-PET for surgical guidance is warranted in the unfavorable intermediate-risk or worse populations. CLINICALTRIALS.GOV IDENTIFIER: NCT04936334.

Patient Navigation Plus Tailored Digital Video Disc Increases Colorectal Cancer Screening Among Low-Income and Minority Patients Who Did Not Attend a Scheduled Screening Colonoscopy: A Randomized Trial.

BACKGROUND: Up to 50% of people scheduled for screening colonoscopy do not complete this test and no studies have focused on minority and low-income populations. Interventions are needed to improve colorectal cancer (CRC) screening knowledge, reduce barriers, and provide alternative screening options. Patient navigation (PN) and tailored interventions increase CRC screening uptake, however there is limited information comparing their effectiveness or the effect of combining them. PURPOSE: Compare the effectiveness of two interventions to increase CRC screening among minority and low-income individuals who did not attend their screening colonoscopy appointment-a mailed tailored digital video disc (DVD) alone versus the mailed DVD plus telephone-based PN compared to usual care. METHODS: Patients (n = 371) aged 45-75 years at average risk for CRC who did not attend a screening colonoscopy appointment were enrolled and were randomized to: (i) a mailed tailored DVD; (ii) the mailed DVD plus phone-based PN; or (iii) usual care. CRC screening outcomes were from electronic medical records at 12 months. Multivariable logistic regression analyses were used to study intervention effects. RESULTS: Participants randomized to tailored DVD plus PN were four times more likely to complete CRC screening compared to usual care and almost two and a half times more likely than those who were sent the DVD alone. CONCLUSIONS: Combining telephone-based PN with a mailed, tailored DVD increased CRC screening among low-income and minority patients who did not attend their screening colonoscopy appointments and has potential for wide dissemination.

Up to half of people scheduled for a screening colonoscopy do not complete this test. There is a need for interventions to improve knowledge about colorectal cancer (CRC) screening, enhance access to screening by offering alternative test options, foster skills for completing screening, and mitigate barriers. The purpose of this study was to compare the effects of two interventions aimed at increasing CRC screening­a mailed tailored digital video disc (DVD) alone versus the mailed DVD plus telephone-based patient navigation (PN)­for patients who had not completed a scheduled screening colonoscopy. We enrolled 371 patients aged 45­75 years who had no CRC risk factors other than age, who were scheduled for a screening colonoscopy but did not attend their appointment. Participants were randomized to receive either: (i) a mailed tailored DVD; (ii) the mailed DVD plus phone-based PN; or (iii) usual care. Those who received the tailored DVD plus PN were four times more likely to complete CRC screening with stool test or colonoscopy compared to usual care. Combining telephone-based PN with a mailed, tailored DVD increased CRC screening among low-income and minority patients who did not attend a scheduled screening colonoscopy appointment.

Possible potential spread of Anopheles stephensi, the Asian malaria vector.

BACKGROUND: Anopheles stephensi is native to Southeast Asia and the Arabian Peninsula and has emerged as an effective and invasive malaria vector. Since invasion was reported in Djibouti in 2012, the global invasion range of An. stephensi has been expanding, and its high adaptability to the environment and the ongoing development of drug resistance have created new challenges for malaria control. Climate change is an important factor affecting the distribution and transfer of species, and understanding the distribution of An. stephensi is an important part of malaria control measures, including vector control. METHODS: In this study, we collected existing distribution data for An. stephensi, and based on the SSP1-2.6 future climate data, we used the Biomod2 package in R Studio through the use of multiple different model methods such as maximum entropy models (MAXENT) and random forest (RF) in this study to map the predicted global An. stephensi climatically suitable areas. RESULTS: According to the predictions of this study, some areas where there are no current records of An. stephensi, showed significant areas of climatically suitable for An. stephensi. In addition, the global climatically suitability areas for An. stephensi are expanding with global climate change, with some areas changing from unsuitable to suitable, suggesting a greater risk of invasion of An. stephensi in these areas, with the attendant possibility of a resurgence of malaria, as has been the case in Djibouti. CONCLUSIONS: This study provides evidence for the possible invasion and expansion of An. stephensi and serves as a reference for the optimization of targeted monitoring and control strategies for this malaria vector in potential invasion risk areas.

Longitudinal association of spirituality with depressive symptom trajectories among older adults in mainland China.

OBJECTIVES: The relationship between spirituality and depressive symptoms among the Chinese elderly is not well known. The current study explores this relationship using longitudinal data and trajectory modeling of depressive symptoms. METHODS: A longitudinal study design was used to measure depressive symptoms repeatedly from 2012 to 2021 using the Geriatric Depression Scale (GDS). Group-based trajectory modeling analysis was conducted to determine the trajectories of depressive symptoms, and multiple logistic regression was used to explore the association between spirituality and depressive symptom trajectories. RESULTS: A total of 2333 participants completed at least two GDS measures, and these were included in the Group-based trajectory modeling analysis. An optimal model of three trajectories was derived: no depressive symptoms group (75.2%), new-onset depressive symptoms group (14.4%), and persistent depressive symptoms group (10.4%). Logistic regression modeling revealed that higher spirituality was associated with a lower risk of both new-onset depressive symptoms (OR = 0.68, 95% CI = 0.49-0.93) and persistent depressive symptoms (OR = 0.32, 95% CI = 0.23-0.45). CONCLUSIONS: Spirituality predicts a lower risk of new-onset depressive symptoms and persistent symptoms among older adults in mainland China.

Assessment of the Learning Curve for a Single-Use Disposable Duodenoscope.

BACKGROUND AND AIMS: In response to documented duodenoscope-related infectious outbreaks of multidrug-resistant organisms, the Food and Drug Administration has recommended a transition to duodenoscopes with innovative designs, including duodenoscopes with disposable components or fully disposable duodenoscopes. We aim to characterize the learning curve (LC) for a single-use disposable duodenoscope. METHODS: We performed a retrospective analysis of a prospectively collected database from 31 patients who underwent ERCP by a single, experienced operator using the EXALT Model D® (Boston Scientific, Marlborough) disposable duodenoscope at a single tertiary referral center. The LC for this device was described by the number of cases needed to achieve proficiency using cumulative sum (CUSUM) analysis. Number of attempts to cannulate and time to cannulate the desired duct were assessed as separate endpoints. The overall mean number of attempts and overall mean time to cannulation were used as the target values in the respective CUSUM analyses. Proficiency was defined as the number of procedures where an inflection point was reached in the CUSUM graph. This observation indicates improving operator performance as shown by a decrease in the number of attempts and shortening of cannulation time after the defined number of procedures. RESULTS: Overall, 31 patients underwent ERCP using the EXALT Model D disposable duodenoscope by a single experienced endoscopist. 6 (19%) patients had a native papilla and the majority of these procedures were classified as ASGE complexity level 2 or above. The procedure was completed using solely the disposable duodenoscope in 27 patients (87%), while a reusable duodenoscope was required for procedure completion in 4 patients (13%). The cross-overs were distributed evenly across the performance period. Procedure-related adverse events included: post-ERCP pancreatitis (3%), bleeding (3%) and no perforations. In the analyses of both endpoints, an inflection of the CUSUM curves is achieved at 10 cases, indicating sustained reduction of cannulation attempts and time to cannulation. CONCLUSION: Among experienced pancreaticobiliary endoscopists, approximately 10 ERCPs is the threshold whereby procedure-related factors including cannulation success and procedural time improves. Procedure-related adverse events are consistent with those expected with reusable duodenoscopes. The need to cross-over from single-use duodenoscope to reusable duodenoscope did not appear to be related to the learning curve, as they were evenly distributed across the study period. These results can be used to guide adoption of single-use duodenoscopes into clinical practice.

The impact of sestamibi scan on clinical decision-making for renal masses: An observational single-center study.

Introduction: We aimed to determine whether sestamibi scan changes management of renal masses. Methods: All patients undergoing sestamibi scan for renal masses between 2008 and 2022 at a single center were retrospectively reviewed. Data were gathered on patient demographics, pre- and postoperative creatinine, sestamibi scan parameters, and cross-sectional imaging characteristics. Outcomes included whether the patient underwent renal mass biopsy or surgical resection and the final pathological diagnosis if tissue was obtained from biopsy or resection. Data regarding postbiopsy as well as postoperative complications were also collected. The odds ratio (OR) for surgery or biopsy based on sestamibi result was calculated. Results: Forty-three patients underwent sestamibi scan from 2008 to 2022, with 10 scans consistent with oncocytoma and 33 with nononcocytoma. The mean tumor size at initial presentation was 4.0 ± 1.8 cm with a median RENAL score of 7 (range: 4-11). For patients with sestamibi scans negative for oncocytoma, the OR for surgery was 12.5 (95% confidence interval [CI]: 2.1-71.2, P = 0.005), and the OR for biopsy was 0.04 (95% CI: 0.005-0.39, P = 0.005). Conversely, for patients with sestamibi scans positive for oncocytoma, the OR for surgery was 0.28 (95% CI: 0.03-2.4, P = 0.24) and the OR for biopsy was 24.0 (95% CI: 2.6-222.7, P = 0.005). Creatinine at the last follow-up was similar between patients with positive and negative sestamibi scans. No patients experienced complications from surgery or biopsy. The median follow-up was 19 months (range: 2-163). Conclusions: A sestamibi scan positive for oncocytoma led to increased use of renal mass biopsy for confirmation. Sestamibi scans that were negative for oncocytoma were more likely to result in surgical resection without biopsy.

[Establishment of a quantitative method for GC analysis of polyoxyethylene (35) castor oil in microemulsion extracts].

With the continuous exploration of microemulsions as solvents for traditional Chinese medicine extraction, polyoxyethy-lene(35) castor oil(CrEL), a commonly used surfactant, is being utilized by researchers. However, the problem of detecting residues of this surfactant in microemulsion extracts has greatly hampered the further development of microemulsion solvents. Based on the chemical structures of the components in CrEL and the content determination method of castor oil in the 2020 edition of the Chinese Pharmacopoeia(Vol. Ⅳ), this study employed gas chromatography(GC) and single-factor experiments to optimize the preparation method of methyl ricinoleate from CrEL. The conversion coefficient between the two was validated, and the optimal sample preparation method was used to process microemulsion extracts of Zexie Decoction from three batches. The content of methyl ricinoleate generated was determined, and the content of CrEL in the microemulsion extracts of Zexie Decoction was calculated using the above conversion coefficient. The results showed that the optimal preparation method for CrEL was determined. Specifically, 10 mL of 1 mol·L~(-1) KOH-methanol solution was heated at 60 ℃ for 15 min in a water bath. Subsequently, 10 mL of boron trifluoride etherate-methanol(1∶3) solution was heated at 60 ℃ for 15 min in a water bath, followed by extraction with n-hexane twice. CrEL could stably produce 20.84% methyl ricinoleate. According to this conversion coefficient, the average mass concentration of CrEL in the three batches of Zexie Decoction microemulsion extracts was 11.94 mg·mL~(-1), which was not significantly different from the CrEL mass concentration of 11.57 mg·mL~(-1) during microemulsion formulation, indicating that the established content determination method of this study was highly accurate, sensitive, and repeatable. It can be used for subsequent research on microemulsion extracts of Zexie Decoction and provide a reference for quality control of other drug formulations containing CrEL.

Understanding the Structural and Catalytic Properties of Al(IV)-2 Acidic Sites of ZSM-5.

It is crucial to identify the structures of active sites to understand how catalysts function and to use that understanding to develop better catalytic materials. ZSM-5 zeolites with dominant Al(IV)-2 sites have been developed in this work. 1H-27Al 2D HMQC and 2D 1H TQ(DQ)-SQ NMR experiments have been performed to investigate the structural properties of this acidic site. The Al(IV)-2 sites have Brønsted and Lewis acid characteristics. The catalytic performance of Al(IV)-2 sites has been tested by n-dodecane cracking reactions. The catalytic results show that the Brønsted acidic strength of the Al(IV)-2 sites is comparable to that of the Al(IV)-1 sites, but the Al(IV)-2 sites' Lewis acid characteristics provide extra catalytic activity. We have gained valuable insights into the characteristics of Al(IV)-2 acid sites within these materials.

Temporal and spatial trend analysis of all-cause depression burden based on Global Burden of Disease (GBD) 2019 study.

Depression has been reported as one of the most prevalent psychiatric illnesses globally. This study aimed to obtain information on the global burden of depression and its associated spatiotemporal variation, by exploring the correlation between the global burden of depression and the social development index (SDI) and associated risk factors. Using data from the Global Burden of Disease study from 1990 to 2019, we described the prevalence and burden of disease in 204 countries across 21 regions, including sex and age differences and the relationship between the global disease burden and SDI. The age-standardized rate and estimated annual percentage change were used to assess the global burden of depression. Individuals with documented depression globally ranged from 182,183,358 in 1990 to 290,185,742 in 2019, representing an increase of 0.59%. More patients experienced major depressive disorder than dysthymia. The incidence and disability-adjusted life years of depression were the highest in the 60-64 age group and much higher in females than in males, with this trend occurring across all ages. The age-standardized incidence and adjusted life-years-disability rates varied with different SDI levels. Relevant risk factors for depression were identified. National governments must support research to improve prevention and treatment interventions.

circSLTM knockdown attenuates chondrocyte inflammation, apoptosis and ECM degradation in osteoarthritis by regulating the miR-515-5p/VAPB axis.

Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage degeneration. Circular RNAs (circRNAs) have emerged as pivotal players in OA progression, orchestrating various biological processes such as proliferation, apoptosis, inflammation, and extracellular matrix (ECM) reorganization. Among these circRNAs, circSLTM exhibits aberrant expression in OA, yet its precise regulatory mechanism remains elusive. This study aimed to elucidate the regulatory mechanisms of circSLTM in OA pathogenesis, with a focus on its role as a competing endogenous RNA (ceRNA). Human cartilage tissues were procured from both OA patients and non-OA individuals, while human chondrocyte cells were subjected to lipopolysaccharide (LPS) treatment to mimic OA-like conditions. Our findings revealed upregulation of circSLTM in OA patients and LPS-treated chondrocytes. Loss-of-function assays were conducted, demonstrating that silencing circSLTM via shRNAs mitigated LPS-induced effects on chondrocytes, as evidenced by enhanced proliferation, reduced apoptosis, and inflammatory factors, and altered expression of extracellular matrix proteins. Further exploration into the regulatory mechanism of circSLTM unveiled its interaction with microRNA-515-5p (miR-515-5p) to modulate vesicle-associated membrane protein (VAPB) expression in chondrocytes. VAPB, also upregulated in OA, was positively regulated by circSLTM. Rescue assays corroborated that VAPB overexpression reinstated the protective effects of circSLTM knockdown on LPS-treated chondrocytes. Moreover, concurrent knockdown of both circSLTM and VAPB demonstrated synergistic protection against LPS-induced chondrocyte injury. Additionally, we delineated that LPS triggered the activation of the NF-κB pathway in chondrocytes, which was counteracted by circSLTM silencing. To assess the effects of circSLTM on OA in vivo, anterior cruciate ligament transection (ACLT) mouse models were established, revealing that circSLTM deficiency ameliorated cartilage defects in vivo. In conclusion, circSLTM exacerbates osteoarthritis progression by orchestrating the miR-515-5p/VAPB axis and activating the NF-κB pathway, providing novel insights for targeted therapy in OA management.

Progress in small-molecule inhibitors targeting PD-L1.

PD-L1 is a transmembrane protein overexpressed by tumor cells. It binds to PD-1 on the surface of T-cells, suppresses T-cell activity and hinders the immune response against cancer. Clinically, several monoclonal antibodies targeting PD-1/PD-L1 have achieved significant success in cancer immunotherapy. Nevertheless, their disadvantages, such as unchecked immune responses, high cost and long half-life, stimulated pharmacologists to develop small-molecule inhibitors targeting PD-1/PD-L1. After a batch of excellent inhibitors with a biphenyl core structure were firstly reported by BMS, more and more researchers focused on small-molecule inhibitors targeting PD-L1 rather than PD-1. Numerous small-molecule inhibitors were extensively designed and synthesized in the past few years. In this paper, the structural characteristics of PD-L1 and complexes of PD-L1 with its inhibitors are elaborated and small molecule inhibitors developed in the last decade are summarized as well. This paper aims to provide insights into further designing and synthesis of small molecule inhibitors targeting PD-L1.

Age-period-cohort analysis of ischemic stroke deaths attributable to physical inactivity in different income regions.

This study assessed the global and regional burden of IS (ischemic stroke) deaths due to LPA (low physical activity) from 1990 to 2019, analyzed regional, sex, and age differences in ASMR (age-standardized mortality rate), and provided a comprehensive understanding of the impact of age, period, and cohort on low physical activity related ischemic stroke ASMR. We conducted an APC (age-period-cohort) analysis of the global and four World Bank income level regions' IS mortality data attributed to LPA from 1990 to 2019, using the GBD2019 database, and the results showed that the global net drift of the Ischemic stroke age-standardized mortality attributable to low physical activity was - 1.085%[95% CI: - 1.168, - 1.003].The ASMR drop is most pronounced in the high-income zone, with a net drift of - 2.473% [95% CI: - 2.759, - 2.187] across the four income groups. The influence of age on mortality is increasing in the worldwide old population, while the period and cohort effects are decreasing. We also performed a Joinpoint regression analysis, which revealed that the specific time of considerable drop in ASMR of IS in the global LPA population was 2002-2007, with an APC of -2.628%. The specific period of considerable drop in ASMR in high-income regions with the highest variation was 1999-2007, with an APC = - 4.726%. The global burden of public health deaths caused by LPA is diminishing, with the most notable progress observed in high-income regions. However, in low and lower-middle income areas, the situation continues to deteriorate. Within the global elderly population, the effects of age on mortality is increasing, while the effects of period and cohort are diminishing. These trends vary across income levels, highlighting the necessity for enhanced international collaboration to formulate context-specific public health strategies aimed at enhancing cardiovascular health on a global, regional, and national scale.

Residents' future residential preference and its affecting factors in the rapid urbanization zone of rural China from a family life cycle perspective.

Understanding farmers' future residential preferences and the factors affecting these choices is crucial for tackling the issues related to hollow village management and rural planning. Despite limited research on the role of the family life cycle, this study explores how the family life cycle, characteristics of the household head, livelihood strategies, and resource availability shape farmers' future residential preferences. Data were collected from 777 households in China's main grain-producing area. The findings reveal that 52.90% of households prefer to stay in their current rural residences. Other favored options are elderly care facilities (13.90%), living with children in the village (12.36%), and ancestral homes (11.68%). The family life cycle significantly affects these preferences (p < 0.01), with changes in family structure and age leading to different living choices. Specifically, households in the initial (71.29%), burden (70.32%), and stable stages (40.14%) prefer their current rural residences, while those in the maintenance and empty-nest stages opt for living with their children's residences (22.22% and 16.96%, respectively) or in elderly care facilities (30.00% and 33.93%). Meanwhile, age, health, income, livelihood strategies, and land ownership also markedly influence the choice of residence. Recommendations include educational programs for elderly rural residents, improving older individuals' adaptability to rural changes, creating more rural employment opportunities, and enhancing medical and infrastructural services for the sustainable rural development.

Bacterial lipase-responsive polydopamine nanoparticles for detection and synergistic therapy of wound biofilms infection.

Wound biofilms represent an elusive conundrum in contemporary treatment and diagnostic options, accredited to their escalating antibiotic resistance and interference in chronic wound healing processes. Here, we developed mesoporous polydopamine (mPDA) nanoparticles, and grafted with rhodamine B (Rb) as biofilm lipase responsive detection probe, followed by π - π stacking mediated ciprofloxacin (CIP) loading to create mP-Rb@CIP nanoparticles. mPDA NPs with a melanin structure could quench fluorescence emissions of Rb. Once encountering biofilm in vivo, the ester bond in Rb and mPDA is hydrolyzed by elevated lipase concentrations, triggering the liberation of Rb and restore fluorescence emissions to achieve real-time imaging of biofilm-infected wounds. Afterwards, the 808 nm near-infrared (NIR) illumination initiates a spatiotemporal controlled antibacterial photothermal therapy (PTT), boosting its effectiveness through photothermal-triggered CIP release for synergistic biofilm eradication. The mP-Rb@CIP platform exhibits dual diagnostic and therapeutic functions, efficaciously treating biofilm-infected wounds in vivo and in vitro. Particularly, the mP-Rb@CIP/NIR procedure expedites wound-healing by alleviating oxidative stress, modulating inflammatory mediators, boosting collagen synthesis, and promoting angiogenesis. Taken together, the theranostic nanosystem strategy holds significant potential for addressing wound biofilm-associated infections.

3D multi-robot olfaction in naturally ventilated indoor environments: Locating a time-varying source at unknown heights.

Source localization is significant for mitigating indoor air pollution and safeguarding the well-being and safety of occupants. While most study focuses on mechanical ventilation and static sources, this study explores the less-explored domain of locating time-varying sources in naturally ventilated spaces. We have developed an innovative 3D localization system that adjusts to varying heights, significantly enhancing capabilities beyond traditional fixed-height 2D systems. To ensure consistency in experimental conditions, we conducted comparative analyses of 2D and 3D methods, using a swinging fan to simulate natural ventilation. Our findings reveal a substantial disparity in performance: the 2D method had a success rate below 46.7% in cases of height mismatches, while our 3D methods consistently achieved success rates above 66.7%, demonstrating their superior effectiveness in complex environments. Furthermore, we validated the 3D strategies in real naturally ventilated settings, confirming their wider applicability. This research extends the scope of indoor source localization and offers valuable insights and strategies for more effective pollution control.

Low Concentration of Wenyang Tonglin Decoction Promotes Conjugation and Transfer of Drug-Resistant Plasmids among Heterologous Strains.

OBJECTIVE: To investigate the effect of low concentration of Wenyang Tonglin Decoction (WTD) on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its mechanism. METHODS: Escherichia coli CP9 (R45) and Staphylococcus aureus RN450RF were cultured in medium containing WTD, and their minimum inhibitory concentration (MIC) values were obtained. Using promoter fusion technology, E. coli CP9 (R45) containing a promoter fusion was obtained. ß-Galactosidase activity of TrfAp and TrbBp was tested, and the mRNA expression of regulatory factors (TrbA, KorA, and KorB) was detected by real-time fluorescent quantitative polymerase chain reaction. RESULTS: The MIC of E. coli CP9 (R45) was 400 g/L and that of S. aureus RN450RF was 200 g/L. When the drug concentration in the culture medium was 200 g/L, the highest number of conjugants was (3.47 ±0.20) × 107 CFU/mL At 90 h of conjugation, the maximum number of conjugants was (1.15 ±0.06) × 108 CFU/mL When the initial bacterial concentration was 108 CFU/mL, the maximum number of conjugants was (3.47 ± 0.20) × 107 CFU/mL. When the drug concentration was 200 g/L, the ß-galactosidase activity of TrfAp and TrbBp significantly increased; the relative quantification of TrbA, KorA and KorB were significantly inhibited. CONCLUSION: Low concentration of WTD promoted the development of bacterial resistance by affecting promoters and inhibiting the expression of regulatory factors.

Ultrasound molecular imaging for early detection of acute renal ischemia-reperfusion injury.

Background: Microcirculatory perfusion disorder and inflammatory response are critical links in acute kidney injury (AKI). We aim to construct anti-vascular cell adhesion molecule-1(VCAM-1) targeted microbubbles (TM) to monitor renal microcirculatory perfusion and inflammatory response. Methods: TM carrying VCAM-1 polypeptide was constructed by biological coupling. The binding ability of TM to human umbilical vein endothelial cells (HUVECs) was detected. Bilateral renal ischemia-reperfusion injury (IRI) models of mice were established to evaluate microcirculatory perfusion and inflammatory response using TM. Thirty-six mice were randomly divided into six groups according to the different reperfusion time (0.5, 2, 6, 12, and 24 h) and sham-operated group (Sham group). The correlation of TM imaging with serum and histopathological biomarkers was investigated. Results: TM has advantages such as uniform distribution, regular shape, high stability, and good biosafety. TM could bind specifically to VCAM-1 molecule expressed by tumor necrosis factor-alpha (TNF-α)-treated HUVECs. In the renal IRI-AKI model, the area under the curve (AUC) of TM significantly decreased both in the renal cortical and medullary after 2 h of reperfusion compared with the Sham group (p < 0.05). Normalized intensity difference (NID) of TM at different reperfusion time was all higher than that of blank microbubbles (BM) and the Sham group (p < 0.05). Ultrasound molecular imaging of TM could detect AKI early before commonly used renal function markers, histopathological biomarkers, and BM imaging. AUC of TM was negatively correlated with serum creatinine (Scr), blood urea nitrogen (BUN), and Cystatin C (Cys-C) levels, and NID of TM was linearly correlated with VCAM-1, TNF-α, and interleukin-6 (IL-6) expression (p < 0.05). Conclusions: Ultrasound molecular imaging based on TM carrying VCAM-1 polypeptide can accurately evaluate the changes in renal microcirculatory perfusion and inflammatory response, which might be a promising modality for early diagnosis of AKI.

Revitalizing premature ovarian failure: quercetin counteracts imatinib-induced apoptosis via the PI3K/AKT signaling pathway based on network pharmacology.

As a commonly used first-line targeted drug, imatinib (Ima) is widely used first-line treatment for cancer patients. Patient survival is significantly prolonged, but Ima can cause premature ovarian failure (POF) and affect fertility. However, the underlying mechanism is unknown, and no effective method can be employed to improve this process. To investigate the effect of quercetin (Que) on Ima-induced POF and the underlying mechanism. The therapeutic impact of Que on Ima-induced POF in mice was clarified via molecular biology experiments and in vivo experiments in animals. To verify the underlying mechanism, network pharmacology was employed to construct a signaling network of Que-Ima-POF-related genes, followed by molecular biology and docking analysis. Network pharmacology analysis identified 38 therapeutic targets of Que in Ima-induced POF. The KEGG pathways of these genes were enriched for the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Molecular docking analysis revealed that the epidermal growth factor receptor (EGFR) is a shared target of Que, Ima, and POF and has strong binding affinity. Hematoxylin-eosin (HE) staining and ELISA confirmed that Que can partially restore the ovarian index and function of mice with Ima-induced POF. Western blot, TUNEL, and immunohistochemical staining confirmed that Que promoted the PI3K/Akt signaling pathway and reduced apoptosis in Ima-induced POF mice. Thus, Que could inhibit apoptosis in Ima-induced POF by activating the PI3K/Akt pathway.