Search

P21-activated kinases (PAKs) are crucial regulators within cellular signaling pathways and have been implicated in a range of human diseases, including cancer. Among the PAK family, PAK2 is widely expressed across various tissues and has emerged as a significant driver of cancer progression. However, systematic studies on PAK2 remain limited. This review provides a comprehensive overview of PAK2's role in cancer, focusing on its involvement in processes such as angiogenesis, metastasis, cell survival, metabolism, immune response, and drug resistance. We also explore its function in key cancer signaling pathways and the potential of small-molecule inhibitors targeting PAK2 for therapeutic purposes. Despite promising preclinical data, no PAK2 inhibitors have reached clinical practice, underscoring challenges related to their specificity and therapeutic application. This review highlights the biological significance of PAK2 in cancer and its interactions with critical signaling pathways, offering valuable insights for future research. We also discuss the major obstacles in developing PAK inhibitors and propose strategies to overcome these barriers, paving the way for their clinical translation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Recent evidence indicates that general anesthesia and sleep-wake behavior share some overlapping neural substrates. GABAergic neurons in the central amygdala (CeA) have a high firing rate during wakefulness and play a role in regulating arousal-related behaviors. The objective of this study is to investigate whether CeA GABAergic neurons participate in the regulation of isoflurane general anesthesia and uncover the underlying neural circuitry., Methods: Fiber photometry recording was used to determine the changes in calcium signals of CeA GABAergic neurons during isoflurane anesthesia in Vgat-Cre mice. Chemogenetic and optogenetic approaches were used to manipulate the activity of CeA GABAergic neurons, and a righting reflex test was used to determine the induction and emergence from isoflurane anesthesia. Cortical electroencephalogram (EEG) recording was used to assess the changes in EEG spectral power and burst-suppression ratio during 0.8% and 1.4% isoflurane anesthesia, respectively. Both male and female mice were used in this study., Results: The calcium signals of CeA GABAergic neurons decreased during the induction of isoflurane anesthesia and was restored during the emergence. Chemogenetic activation of CeA GABAergic neurons delayed induction time (mean ± SD, vehicle vs. clozapine-N-oxide: 58.75±5.42 s vs. 67.63±5.01 s; n=8, P=0.0017) and shortened emergence time (385.50±66.26 s vs. 214.60±40.21 s; n=8, P=0.0017) from isoflurane anesthesia. Optogenetic activation of CeA GABAergic neurons produced a similar effect. Furthermore, optogenetic activation decreased EEG delta power (Pre-stim vs. Stim: 46.63%±4.40% vs. 34.16%±6.47%; n=8, P=0.0195) and burst-suppression ratio (83.39%±5.15% vs. 52.60%±12.98%; n=8, P=0.0002). Moreover, optogenetic stimulation of terminals of CeA GABAergic neurons in the basal forebrain (BF) also promoted cortical activation and accelerated behavioral emergence from isoflurane anesthesia., Conclusions: Our results suggest that CeA GABAergic neurons play a role in general anesthesia regulation, which facilitates behavioral and cortical emergence from isoflurane anesthesia through the GABAergic CeA-BF pathway., Competing Interests: Conflicts of Interest: The authors have no competing financial interests or potential conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Anesthesiologists.)

Objectives: To explore the role of nodule-pleural relationship, including nodule with pleural tail sign (PTS), nodule with pleural contact and nodule with pleural unrelated in CT-guided percutaneous transthoracic needle biopsy (PTNB)-induced pneumothorax, and whether employing different puncture routes has an impact on the incidence of pneumothorax in PTNB of nodules with PTS., Methods: Between April 1, 2019, to June 30, 2021, 775 consecutive PTNB procedures of pulmonary nodules in the Peking University Cancer Hospital were retrospectively reviewed. The univariate and multivariate regression analysis were used to identify the risk factors for pneumothorax in PTNB., Results: The nodule with pleural contact group has a lower incidence of pneumothorax than the nodule with PTS group (p = 0.001) and the nodule with pleural unrelated group (p = 0.002). It was observed that a higher incidence of pneumothorax caused by crossing PTS compared with no crossing PTS (p < 0.001). Independent risk factors for pneumothorax included crossing PTS (p < 0.001), perifocal emphysema (p < 0.001), biopsy side up (p < 0.001), longer puncture time (p < 0.001), deeper needle insertion depth (intrapulmonary) (p < 0.001) and nodules in the middle or lower lobe (p = 0.007)., Conclusion: Patients with crossing PTS, a nodule in the middle or lower lobe, longer puncture time, biopsy side up, deeper needle insertion depth (intrapulmonary), and perifocal emphysema were more likely to experience pneumothorax in PTNB. When performing the biopsy on a nodule with PTS, selecting a route that avoids crossing through the PTS may be advisable to reduce the risk of pneumothorax., (© 2024. The Author(s).)

Objective: To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML). Methods: A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping. Results: Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z= -2.381, P =0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2 =6.760, P =0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR =2.54, 95% CI : 1.68-3.84, P <0.001), hemoglobin (HB) ( OR =0.96, 95% CI : 0.93-0.99, P <0.05), and bone marrow blast (BM blast) ( OR =1.07, 95% CI : 1.02-1.13, P <0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI : 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI : 0.890-0.973); C-index=0.925 (95% CI : 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z= 1.693, P >0.05). Conclusion: Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

Considering animal welfare, the free-range laying hen farming model is increasingly gaining attention. However, in some countries, large-scale farming still relies on the cage-rearing model, making the focus on the welfare of caged laying hens equally important. To evaluate the health status of caged laying hens, a dataset comprising visible light and thermal infrared images was established for analyses, including morphological, thermographic, comb, and behavioral assessments, enabling a comprehensive evaluation of the hens' health, behavior, and population counts. To address the issue of insufficient data samples in the health detection process for individual and group hens, a dataset named BClayinghens was constructed containing 61,133 images of visible light and thermal infrared images. The BClayinghens dataset was completed using three types of devices: smartphones, visible light cameras, and infrared thermal cameras. All thermal infrared images correspond to visible light images and have achieved positional alignment through coordinate correction. Additionally, the visible light images were annotated with chicken head labels, obtaining 63,693 chicken head labels, which can be directly used for training deep learning models for chicken head object detection and combined with corresponding thermal infrared data to analyze the temperature of the chicken heads. To enable the constructed deep-learning object detection and recognition models to adapt to different breeding environments, various data enhancement methods such as rotation, shearing, color enhancement, and noise addition were used for image processing. The BClayinghens dataset is important for applying visible light images and corresponding thermal infrared images in the health detection, behavioral analysis, and counting of caged laying hens under large-scale farming.

Three previously undescribed protoilludane-type sesquiterpene aryl esters, armillanals A-C (1-3), along with seven known ones (4-10) were obtained from Armillaria gallica Marxm. & Romagn. Compounds 1 and 2 were a rare class of sesquiterpenes featuring the Δ 2(3) and Δ 12(13) -protoilludane skeleton. Their structures were established by extensive spectroscopic methods. Based on electronic circular dichroism (ECD) calculations, the absolute configurations of three new compounds (1-3) were determined. The anti-inflammatory activity of compounds 1-10 was screened and compound 3 could dose-dependently decrease the level of lactate dehydrogenase, showing IC 50 value of 4.525 μM., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Ethnopharmacological Relevance: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia., Aim of the Study: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia., Materials and Methods: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR)., Results: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 μg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS., Conclusions: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Robust constrained formation tracking control of underactuated underwater vehicles (UUVs) fleet in 3-D space is a challenging but practical problem. To address this problem, this article develops a novel consensus-based optimal coordination protocol and a robust controller, which adopts a hierarchical architecture. On the top layer, the spherical coordinate transform is introduced to tackle the nonholonomic constraint, and then a distributed optimal motion coordination strategy is developed. As a result, the optimal formation tracking of UUVs fleet can be achieved, and the constraints are fulfilled. To realize the generated optimal commands better and, meanwhile, deal with the underactuation, at the lower-level control loop a neurodynamics-based robust backstepping controller is designed, and in particular, the issue of "explosion of terms" appearing in conventional backstepping-based controllers is avoided and control activities are improved. The stability of the overall UUVs formation system is established to ensure that all the states of the UUVs are uniformly ultimately bounded in the presence of unknown disturbances. Finally, extensive simulation comparisons are made to illustrate the superiority and effectiveness of the derived optimal formation tracking protocol.

Isobavachalcone (IBC) is a natural small molecule with various biological activities; however, its inhibitory effects on Cryptococcus neoformans remain unclear. In our study, IBC showed a good antifungal effect. Through in vitro experiments, its minimum inhibitory concentration was 0.5-1 µg/mL. It exhibited the same antifungal effect as Amphotericin B in brain and lung infections in in vivo experiments. IBC also showed a synergistic antifungal effect with emodin with lower toxicity, and C. neoformans did not develop drug resistance to IBC. In the mechanistic study, significantly damaged mitochondria of C. neoformans, a significant reduction in mitochondrial membrane potential and adenosine triphosphate production, and an increase in hydrogen peroxide (H 2 O 2 ) caused by IBC were observed using transmission electron microscopy. Through drug affinity-responsive target stability combined with phenotype detection, riboflavin synthases of aconitase and succinate dehydrogenase were screened. Molecular docking, quantitative polymerase chain reaction experiments, target inhibitor and agonist intervention, molecular interaction measurements, and minimum inhibitory concentration detection of the constructed expression strains revealed that IBC targeted the activity of these two enzymes, interfered by the tricarboxylic acid cycle, inhibited the production of adenosine triphosphate, blocked electron transport, reduced mitochondrial membrane potential, and induced antioxidation imbalance and reactive oxygen species accumulation, thus producing an antifungal effect. Therefore, IBC is a promising lead drug and redox antifungal agent for C. neoformans., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Ten-eleven-translocation (TET) 2 is a member of the TET family of proteins (TET1-3). DNMT1 gene deletion confers resistance to DNA methyltransferase (DNMT) inhibitors in colorectal, breast, and ovarian cancer cells. Currently, the effect of DNMT1 gene status on TET2 phenotype following DNMT inhibitor treatment is unclear in human malignancies., Methods: Human colorectal carcinoma HCT116 cells ( DNMT +/+ ) and their isogenic DNMT1 knockout ( DNMT1 -/- ) counterpart were treated with DNMT inhibitors. Expression of TET2 and tumor suppressor (p16 ink4A and p15 ink4B ) proteins were examined by Western blot. Apoptosis and CDKN2A promoter demethylation following drug treatment were detected by Annexin-V apoptosis assay and methylation-specific PCR., Results: TET2 expression was robustly increased in DNMT1 -/- cells by 0.5 µM and 5 µM decitabine and azacitidine treatment. Augmentation of TET2 expression was accompanied by re-expression of p16 ink4A and p15 ink4B proteins and CDKN2A promoter demethylation. TET2 upregulation and tumor suppressor re-expression were associated with resistance conferred by DNMT1 deletion. Treatment with 5-aza-4'-thio-2'-deoxycytidine at a low 0.5 µM dose only upregulated TET2 and reduced CDKN2A promoter methylation, and re-expression of p16 ink4A in DNMT1 -/- cells. DNMT inhibitors showed minimal effects on TET2 upregulation and re-expression of tumor suppressor proteins in cells with intact DNMT1 ., Conclusions: DNMT1 gene deletion made cancer cells prone to TET2 upregulation and activation of tumor suppressor expression upon DNMT inhibitor challenge. TET2 augmentation is concomitant with resistance to DNMT inhibitors in a DNMT1 -deleted state.

Background: Recurrence score (RS) based on a 21-gene genomic assay is frequently used to estimate risk of distant recurrence for choice of adjuvant chemotherapy in breast cancer. It remains unclear whether RS is an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) in the TAILORx trial population., Methods: We evaluated the association of RS with BCSS and OS plus recurrence-free interval (RFI) and invasive disease-free survival (DFS) using multivariable Cox proportional hazards regression analysis, adjusting for clinicopathologic measures, in 8,916 patients with hormone receptor-positive, HER2-negative, node-negative breast cancer. Likelihood ratio (LR) test was used to assess the relative amount of prognostic information provided by RS to BCSS, OS, RFI, and DFS, comparatively., Results: Event rates for BCSS, OS, RFI, and DFS were 1.7%, 5.2%, 5.6%, and 12.6%, respectively, by up to 11.6 years of follow-up. Compared with low-range RS (0-10), patients with midrange (11-25) and high-range (26-100) RS had inferior BCSS (adjusted hazard ratio [aHR], 5.12 [95% CI, 2.09-16.92] and 8.03 [95% CI, 2.91-28.47], respectively) and RFI (aHR, 1.68 [95% CI, 1.23-2.36] and 3.05 [95% CI, 2.02-4.67], respectively), independent of clinicopathologic factors. High-range score was associated with an increased risk of DFS (aHR, 1.56 [95% CI, 1.20-2.04]) but not significantly associated with OS (aHR, 1.44 [95% CI, 0.95-2.18]). Midrange score was associated with neither DFS (aHR, 1.15 [95% CI, 0.96-1.38]) nor OS (HR 1.14 [95% CI, 0.87-1.52]). LR-χ2 values were 83.0 and 65.1 for RFI and BCSS, respectively, and 17.5 and 33.6 for OS and DFS, respectively (P<.0001)., Conclusions: RS is an independent measure for BCSS and recurrence prognoses relative to OS in early-stage breast cancer. It carries more prognostic information for breast cancer-specific outcomes.

The research on automatic monitoring methods for greenhouse gases and hazardous gas emissions is currently a focal point in the fields of environmental science and climatology. Until 2023, the amount of greenhouse gases emitted by the livestock sector accounts for about 11-17% of total global emissions, with enteric fermentation in ruminants being the main source of the gases. With the escalating problem of global climate change, accurate and effective monitoring of gas emissions has become a top priority. Presently, the determination of gas emission indices relies on specialized instrumentation such as breathing chambers, greenfeed systems, methane laser detectors, etc., each characterized by distinct principles, applicability, and accuracy levels. This paper first explains the mechanisms and effects of gas production by ruminant production systems, focusing on the monitoring methods, principles, advantages, and disadvantages of monitoring gas concentrations, and a summary of existing methods reveals their shortcomings, such as limited applicability, low accuracy, and high cost. In response to the current challenges in the field of equipment for monitoring greenhouse and hazardous gas emissions from ruminant production systems, this paper outlines future perspectives with the aim of developing more efficient, user-friendly, and cost-effective monitoring instruments.

INTRODUCTION: Most airline pilots reported having suffered from sleep disorders and fatigue due to circadian disruption, a potential risk to flight safety. This study attempted to uncover the actual scenario of circadian disruption and working load status among airline pilots. METHODS: In study 1, 21 pilots were invited to participate in a 14-d sleep monitoring and a dual 2-back test to monitor their sleep patterns and cognitive function level. To provide an in-depth view, data from scheduled flights, including 567 airline pilots, was analyzed in Study 2. The present study used cluster analysis to reflect the distribution of the flight scheduling characteristics, including working time and actual working hours. A simulation model was then developed to predict the pilots' 1-mo sleep-wake pattern. RESULTS: The results indicated that sleep problems were prevalent in this population, especially the night before an earlier morning shift. Regarding the cognitive test, they scored the lowest on earlier morning shifts compared with daytime and evening shifts. It was found that over 70% of the flight schedules can lead to circadian disruption, and 47.44% of the pilots worked under high-load status. DISCUSSION: Airline pilots inevitably work irregular hours and the current policies for coping with circadian disruption seem inefficient. This study thus calls for urgency in improving scheduling and fatigue management systems from the circadian rhythm perspective. Yang SX, Cheng S, Sun Y, Tang X, Huang Z. Circadian disruption in civilian airline pilots . Aerosp Med Hum Perform. 2024; 95(7):381-389.

Two new triterpenes mayteneri A ( 1 ), mayteneri B ( 2 ), and seven known compounds ( 3-9 ) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3 - 9 were determined by comparison of their spectral with those reported. Compounds 4 - 7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC 50 values of 2.36-3.44  μ M.

Environmental lipids are essential for fueling tumor energetics, but whether these exogenous lipids transported into cancer cells facilitate immune escape remains unclear. Here, we find that CD36, a transporter for exogenous lipids, promotes acute myeloid leukemia (AML) immune evasion. We show that, separately from its established role in lipid oxidation, CD36 on AML cells senses oxidized low-density lipoprotein (OxLDL) to prime the TLR4-LYN-MYD88-nuclear factor κB (NF-κB) pathway, and exogenous palmitate transfer via CD36 further potentiates this innate immune pathway by supporting ZDHHC6-mediated MYD88 palmitoylation. Subsequently, NF-κB drives the expression of immunosuppressive genes that inhibit anti-tumor T cell responses. Notably, high-fat-diet or hypomethylating agent decitabine treatment boosts the immunosuppressive potential of AML cells by hijacking CD36-dependent innate immune signaling, leading to a dampened therapeutic effect. This work is of translational interest because lipid restriction by US Food and Drug Administration (FDA)-approved lipid-lowering statin drugs improves the efficacy of decitabine therapy by weakening leukemic CD36-mediated immunosuppression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Accumulating salinity in soil critically affected growth, development, and yield in plant. However, the mechanisms of plant against salt stress largely remain unknown. Herein, we identified a gene named SmCYP78A7a, which encoded a cytochrome P450 monooxygenase and belonged to the CYP78A sub-family, and its transcript level was significantly up-regulated by salt stress and down-regulated by dehydration stress. SmCYP78A7a located in the endoplasmic reticulum. Silencing of SmCYP78A7a enhanced susceptibility of eggplant to salt stress, and significantly down-regulated the transcript levels of salt stress defense related genes SmGSTU10 and SmWRKY11 as well as increased hydrogen peroxide (H 2 O 2 ) content and decreased catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) enzyme activities. In addition, SmCYP78A7a transient expression enhanced eggplant tolerance to salt stress. By chromatin immunoprecipitation PCR (ChIP-PCR), luciferase reporter assay, and electrophoretic mobility shift assay (EMSA), SmWRKY11 activated SmCYP78A7a expression by directly binding to the W-box 6-8 (W-box 6, W-box 7, and W-box 8) within SmCYP78A7a promoter to confer eggplant tolerance to salt stress. In summary, our finds reveal that SmCYP78A7a positively functions in eggplant response to salt stress via forming a positive feedback loop with SmWRKY11, and provide a new insight into regulatory mechanisms of eggplant to salt stress., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Both neuroinflammation and iron accumulation play roles in the pathogenesis of Parkinson's disease (PD). However, whether inflammation induces iron dyshomeostasis in dopaminergic neurons at an early stage of PD, at which no quantifiable dopaminergic neuron loss can be observed, is still unknown. As for the inflammation mediators, although several cytokines have been reported to increase in PD, the functions of these cytokines in the SN are double-edged and controversial. In this study, whether inflammation could induce iron dyshomeostasis in dopaminergic neurons through high mobility group protein B1 (HMGB1) in the early stage of PD is explored. Lipopolysaccharide (LPS), a toxin that primarily activates glia cells, and 6-hydroxydopamine (6-OHDA), the neurotoxin that firstly impacts dopaminergic neurons, were utilized to mimic PD in rats. We found a common and exceedingly early over-production of HMGB1, followed by an increase of divalent metal transporter 1 with iron responsive element (DMT1+) in the dopaminergic neurons before quantifiable neuronal loss. HMGB1 neutralizing antibody suppressed inflammation in the SN, DMT1+ elevation in dopaminergic neurons, and dopaminergic neuronal loss in both LPS and 6-OHDA administration- induced PD models. On the contrary, interleukin-1β inhibitor diacerein failed to suppress these outcomes induced by 6-OHDA. Our findings not only demonstrate that inflammation could be one of the causes of DMT1+ increase in dopaminergic neurons, but also highlight HMGB1 as a pivotal early mediator of inflammation-induced iron increase and subsequent neurodegeneration, thereby HMGB1 could serve as a potential target for early-stage PD treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This article addresses distributed robust learning-based control for consensus formation tracking of multiple underwater vessels, in which the system parameters of the marine vessels are assumed to be entirely unknown and subject to the modeling mismatch, oceanic disturbances, and noises. Toward this end, graph theory is used to allow us to synthesize the distributed controller with a stability guarantee. Due to the fact that the parameter uncertainties only arise in the vessels' dynamic model, the backstepping control technique is then employed. Subsequently, to overcome the difficulties in handling time-varying and unknown systems, an online learning procedure is developed in the proposed distributed formation control protocol. Moreover, modeling errors, environmental disturbances, and measurement noises are considered and tackled by introducing a neurodynamics model in the controller design to obtain a robust solution. Then, the stability analysis of the overall closed-loop system under the proposed scheme is provided to ensure the robust adaptive performance at the theoretical level. Finally, extensive simulation experiments are conducted to further verify the efficacy of the presented distributed control protocol.

Cochlioquinones are a member of meroterpenoids that partially possessed phenolic hydroxyls with potential antioxidant activities. This study investigated the mass fragmentation pathways, antioxidant, cytotoxic, and phytotoxic activities of cochlioquinone analogs. The mass fragmentation pathways of cochlioquinones (1-7) were firstly analyzed using UPLC-Q-TOF-MS/MS, in which Retro Diels-Alder reaction, neutral loss, and McLafferty rearrangement were the main cleavage patterns. Compound 8 and 9 (a unique new analog) were then isolated in target. Cochlioquinones (4-6, 9) displayed strong antioxidant activities for DPPH radical scavenging assay as the first antioxidant effects report. In addition, 1-9 exhibited cytotoxic activities against B16 cells (IC50 from 1.91 to 12.33 μM) and Hep G2 cells (IC50 from 3.21 to 77.15 μM), and 5, 7, and 8 showed phytotoxic activities against foxtail leaves. These biological activities imply that cochlioquinones can be as antioxidant agents for food additives or bioactive molecules for cancer drugs and pesticides., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In complex and dynamic environments, traditional pursuit-evasion studies may face challenges in offering effective solutions to sudden environmental changes. In this paper, a bio-inspired neural network (BINN) is proposed that approximates a pursuit-evasion game from a neurodynamic perspective instead of formulating the problem as a differential game. The BINN is topologically organized to represent the environment with only local connections. The dynamics of neural activity, characterized by the neurodynamic shunting model, enable the generation of real-time evasive trajectories with moving or sudden-change obstacles. Several simulation and experimental results indicate that the proposed approach is effective and efficient in complex and dynamic environments.

The geographic expansion of Homo sapiens populations into southeastern Europe occurred by ∼47,000 years ago (∼47 ka), marked by Initial Upper Palaeolithic (IUP) technology. H. sapiens was present in western Siberia by ∼45 ka, and IUP industries indicate early entries by ∼50 ka in the Russian Altai and 46-45 ka in northern Mongolia. H. sapiens was in northeastern Asia by ∼40 ka, with a single IUP site in China dating to 43-41 ka. Here we describe an IUP assemblage from Shiyu in northern China, dating to ∼45 ka. Shiyu contains a stone tool assemblage produced by Levallois and Volumetric Blade Reduction methods, the long-distance transfer of obsidian from sources in China and the Russian Far East (800-1,000 km away), increased hunting skills denoted by the selective culling of adult equids and the recovery of tanged and hafted projectile points with evidence of impact fractures, and the presence of a worked bone tool and a shaped graphite disc. Shiyu exhibits a set of advanced cultural behaviours, and together with the recovery of a now-lost human cranial bone, the record supports an expansion of H. sapiens into eastern Asia by about 45 ka., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To explore the effects and improvement needs of an outreach dental care programme (ODCP) for older adults using residential care or daycare services from the perspectives of the caregivers, the dentists and administrative staff involved in the implementation of the ODCP., Methods: A qualitative study was conducted through semi-structured interviews with three stakeholders, long-term care (LTC) facility caregivers, administrative staff and dentists working for the ODCP. Combined maximum variation and snowball sampling strategies were adopted, and 22, 9 and 7 participants were interviewed from each stakeholder, respectively. The interviews were conducted via telephone, which were audio-recorded and transcribed verbatim for analysis. NVivo software was used for storing and analysing the data. Data analysis was conducted continuously during the study., Results: Most participants opined that the ODCP benefited older adults by raising their oral health conditions and awareness. However, they complained of the complicated administrative procedures, unmet dental treatment needs, inefficient coordination, unclear work guidelines and shortage of dental manpower. More advanced dental treatment options, better coordination among different parties, simpler administrative processes and better incentives for dentists were proposed to further improve the programme., Conclusions: According to the stakeholders, ODCP seems beneficial to older adults using LTC services. Further improvements in the scope of dental treatments, cooperation between the outreach dental teams and caregivers, and streamlining of the administrative process are needed for the provision of effective outreach dental care to satisfy the unmet treatment needs of older adults who use LTC services. Better incentives are needed to attract and retain dentists., (© 2023 The Authors. Gerodontology published by Gerodontology Association and John Wiley & Sons Ltd.)

Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were administered a single dose of gefitinib and the blood samples were used for quantifying the concentration of gefitinib and genotyping fifteen single-nucleotide polymorphisms of cytochrome P450 enzymes (CYP3A4, CYP3A5, CYP2D6, CYP2C9 and CYP2C19) and drug transporters (ABCB1 and ABCG2).CYP3A5*3 (rs776746) polymorphism showed a significant influence, with higher gefitinib AUC 0-t in carrier of CC genotype than in CT/TT genotype (BH-adjusted p value <0.05). For CYP2C9*3 (rs1057910), significant differences in pharmacokinetics of gefitinib were detected between carriers of AA and AC genotypes, with higher AUC 0-t, AUC 0-∞ and C max in carrier of AC genotype than in AA gen-otype (BH-adjusted p value <0.05). No associations were found between SNPs in CYP3A4, CYP2D6, CYP2C19, ABCB1, ABCG2 and the pharmacokinetics of gefitinib.The SNPs in CYP3A5*3 (rs776746) and CYP2C9*3 (rs1057910) were found to be associated with altered gefitinib pharmacokinetics in healthy Chinese volunteers.

This paper proposes a novel intelligent approach to swarm robotics, drawing inspiration from the collective foraging behavior exhibited by fish schools. A bio-inspired neural network (BINN) and a self-organizing map (SOM) algorithm are used to enable the swarm to emulate fish-like behaviors such as collision-free navigation and dynamic sub-group formation. The swarm robots are designed to adaptively reconfigure their movements in response to environmental changes, mimicking the flexibility and robustness of fish foraging patterns. The simulation results show that the proposed approach demonstrates improved cooperation, efficiency, and adaptability in various scenarios. The proposed approach shows significant strides in the field of swarm robotics by successfully implementing fish-inspired foraging strategies. The integration of neurodynamic models with swarm intelligence not only enhances the autonomous capabilities of individual robots, but also improves the collective efficiency of the swarm robots.

Ubiquitin-specific protease 22 (USP22) is a member of the ubiquitin specific protease family (ubiquitin-specific protease, USPs), the largest subfamily of deubiquitinating enzymes, and plays an important role in the treatment of tumors. USP22 is also expressed in the heart. However, the role of USP22 in heart disease remains unclear. In this study, we found that USP22 was elevated in hypertrophic mouse hearts and in angiotensin II (Ang II)-induced cardiomyocytes. The inhibition of USP22 expression with adenovirus significantly rescued hypertrophic phenotype and cardiac dysfunction induced by pressure overloaded. Consistent with in vivo study, silencing by USP22 shRNA expression in vitro had similar results. Molecular analysis revealed that transforming growth factor-β-activating protein 1 (TAK1)-(JNK1/2)/P38 signaling pathway and HIF-1α was activated in the Ang II-induced hypertrophic cardiomyocytes, whereas HIF-1α expression was decreased after the inhibition of USP22. Inhibition of HIF-1α expression reduces TAK1 expression. Co-immunoprecipitation and ubiquitination studies revealed the regulatory mechanism between USP22 and HIF1α.Under hypertrophic stress conditions, USP22 enhances the stability of HIF-1α through its deubiquitination activity, which further activates the TAK1-(JNK1/2)/P38 signaling pathway to lead to cardiac hypertrophy. Inhibition of HIF-1α expression further potentiates the in vivo pathological effects caused by USP22 deficiency. In summary, this study suggests that USP22, through HIF-1α-TAK1-(JNK1/2)/P38 signaling pathway, may be potential targets for inhibiting pathological cardiac hypertrophy induced by pressure overload., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Gene tree discordance is a significant legacy of biological evolution. Multiple factors can result in incongruence among genes, such as introgression, incomplete lineage sorting (ILS), gene duplication or loss. Resolving the background of gene tree discordance is a critical way to uncover the process of species diversification. Camellia, the largest genus in Theaceae, has controversial taxonomy and systematics due in part to a complex evolutionary history. We used 60 transcriptomes of 55 species, which represented 15 sections of Camellia to investigate its phylogeny and the possible causes of gene tree discordance. We conducted gene tree discordance analysis based on 1,617 orthologous low-copy nuclear genes, primarily using coalescent species trees and polytomy tests to distinguish hard and soft conflict. A selective pressure analysis was also performed to assess the impact of selection on phylogenetic topology reconstruction. Our results detected different levels of gene tree discordance in the backbone of Camellia, and recovered rapid diversification as one of the possible causes of gene tree discordance. Furthermore, we confirmed that none of the currently proposed sections of Camellia was monophyletic. Comparisons among datasets partitioned under different selective pressure regimes showed that integrating all orthologous genes provided the best phylogenetic resolution of the species tree of Camellia. The findings of this study reveal rapid diversification as a major source of gene tree discordance in Camellia and will facilitate future investigation of reticulate relationships at the species level in this important plant genus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: To evaluate the effects of an outreach dental care program (ODCP) on the oral health status and oral health-related quality of life (OHRQoL) of older adults who used residential or day care services in Hong Kong., Methods: Older adults who had received dental treatments provided in the ODCP were recruited. Clinical examinations were performed by one calibrated examiner (SXY) at baseline and 1-year follow-up in the residential homes or day care centres. Face-to-face interviews were conducted using the transition scale of the Oral Health Impacts on Daily Living (OHIDL) questionnaire to investigate the perceived change in OHRQoL at baseline, 2-month and 1-year follow-ups. The Wilcoxon matched-pair signed-rank test or McNemar/McNemar-Bowker test was used to explore the change in oral health status after dental treatments. Factors associated with the perceived change in OHRQoL were explored with binary logistic regression., Results: Four hundred and thirteen older adults (mean age = 83.8 years) participated in the study at baseline, and 377 (91.3%) and 359 (86.9%) were successfully followed 2 months and 1 year after receiving the outreach dental service, respectively. At the 1-year follow-up, the number of decayed teeth and functional tooth units, and the prevalence of poor denture hygiene decreased while there was more dental plaque deposition and a higher proportion of participants with gingival bleeding upon probing. More than 50% of the participants perceived no change or an improvement in OHRQoL in all domains at both follow-ups. Older adults who perceived their oral health status as 'healthy or fair' and those who suffered from toothache at baseline had a higher chance to perceive having a better or at least the same OHRQoL at the 2-month and 1-year follow-ups, respectively., Conclusions: The ODCP in Hong Kong can solve some of the dental problems of older adults using long-term care services and keep most of them from deterioration in OHRQoL, especially those suffering from toothache., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Reducing losses caused by pathogens is an effective strategy for stabilizing crop yields. Daunting challenges remain in cloning and characterizing genes that inhibit stripe rust, a devastating disease of wheat (Triticum aestivum) caused by Puccinia striiformis f. sp. tritici (Pst). We found that suppression of wheat zeaxanthin epoxidase 1 (ZEP1) increased wheat defense against Pst. We isolated the yellow rust slower 1 (yrs1) mutant of tetraploid wheat in which a premature stop mutation in ZEP1-B underpins the phenotype. Genetic analyses revealed increased H 2 O 2 accumulation in zep1 mutants and demonstrated a correlation between ZEP1 dysfunction and slower Pst growth in wheat. Moreover, wheat kinase START 1.1 (WKS1.1, Yr36) bound, phosphorylated, and suppressed the biochemical activity of ZEP1. A rare natural allele in the hexaploid wheat ZEP1-B promoter reduced its transcription and Pst growth. Our study thus identified a novel suppressor of Pst, characterized its mechanism of action, and revealed beneficial variants for wheat disease control. This work opens the door to stacking wheat ZEP1 variants with other known Pst resistance genes in future breeding programs to enhance wheat tolerance to pathogens., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

River ecological health assessments are the premise for protecting river biodiversity and curbing river water environment deterioration. To explore the river ecosystem health status and its response mechanism to water environmental factors in the middle reaches of the Yarlung Zangbo River, phytoplankton samples were collected during July and October 2021, and water environmental factors were measured. The phytoplankton species were identified, and their cell abundance and biomass were calculated. The phytoplankton integrity index was constructed to evaluate the ecological health status of the river. The temporal and spatial distribution characteristics of water environmental factors and phytoplankton community, as well as the correlation between P-IBI value and community parameters and water environmental factors were analyzed. The results showed that the difference in water environmental factors was not evident in time but was significant in space. The average cell abundance and biomass of phytoplankton were in the order of wet season>dry season and main stream>tributaries. Diatoms dominated the community, and pH and WT were the major water environmental factors driving the spatial and temporal distributions of phytoplankton. The ecological health status of the middle reaches of the Yarlung Zangbo River was "healthy to sub-healthy." The river health status was better than that of the dry season, and that of the tributaries was better than that of the main stream. EC, TUR, WT, NO 3 - -N, and NH 4 + -N were the major water environmental factors affecting the ecological health status of the river reach, which could be affected by the direction and rate of phytoplankton community succession. It is involved in and affects the process of material circulation and energy flow of the river ecosystem, thereby driving the ecological health of the middle reaches of the Yarlung Zangbo River.

Background: Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori ( H. pylori ) infections. Therefore, there is an urgent need to develop new antimicrobial agents to replace antibiotics. Our previous study found that linolenic acid-metronidazole (Lla-Met) has a good antibacterial effect against H. pylori, both antibiotic-resistant and sensitive H. pylori . Also, H. pylori does not develop resistance to Lla-Met. Therefore, it could be used for preparing broad-spectrum antibacterial agents. However, since the antibacterial mechanism of Lla-Met is not well understood, we explored this phenomenon in the present study., Aim: To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections., Methods: H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified., Results: Lla-Met treatment induced several changes in H. pylori cells, including roughening and swelling. In vivo experiments revealed that Lla-Met induced oxidation, DNA fragmentation, and phosphatidylserine ectropionation in H. pylori cells. Inhibiting Lla-Met with L-cysteine abrogated the above phenomena. Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes, both anti-oxidation-related genes., Conclusion: Lla-Met kills H. pylori mainly by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the feasibility and safety of a robotic surgical system (or laparoscopy) in combination with colonoscopy (combined) for the treatment of stage T1N0M0 colorectal cancer. Methods: This was a descriptive case series. Indications for combined dual-scope surgery in this study were as follows: (1) preoperative colonoscopic examination of lesions in the middle and upper rectum and colon with pathologically confirmed high-grade intraepithelial neoplasia, intramucosal adenocarcinoma, or adenocarcinoma; (2) no distant or local lymph node metastases; and (3) endoscopic ultrasound and magnetic resonance imaging evidence of tumor invasion of the mucosal or submucosal, but not the muscular, layer (i.e., T1). The clinical data of 13 patients with stage T1 colorectal cancer who had undergone dual-scope combined resection using a robotic surgery system or laparoscope-assisted combined colonoscopy surgery at the First Affiliated Hospital of Zhengzhou University from April to October 2022 were retrospectively collected, including 6 males and 7 females, with a median age of 59 (48~88) years old. The tumors were located in the upper and middle rectum in six patients, in the sigmoid colon in three, and in the ascending colon in four. The median maximum diameter of the tumors was 3.0 (1.8-5.0) cm. The surgery was performed by a robotic surgery system (or laparoscopy) with peritumoral D1 lymph node dissection at the first station in the tumor area. The tumors were resected under direct vision and the defects in the intestinal wall were using a robotic surgery system (or laparoscopy). A robotic surgery system was combined with colonoscopy in eight cases and laparoscopy combined with colonoscopy in the remaining five. Studied variables includes surgical and pathological features, postoperative factors, and outcomes. Results: Surgery was successful in all 13 patients with no need for conversion to open surgery or intraoperative blood transfusion. The median operating time was 85 (60-120) minutes, median intraoperative bleeding 3 (2-5) mL, median number of lymph nodes harvested 3 (1-5), and the median circumferential resection margin 0.8 (0.5-1.0) cm. Postoperative pathological examination showed lymph node metastasis in one patient, who therefore underwent additional radical surgery. The median postoperative time to ambulation was 1 (1-2) days. The urinary catheters of all patients were removed 1 day after surgery and the median length of stay was 4 (3-5) days. No abdominal infection, anastomotic leakage or bleeding occurred in any of the study patients. The median follow-up time was 10 (6-12) months, during which no tumor recurrence or metastasis was found, and the quality of life was satisfactory. Conclusions: The combination of two minimally invasive platforms, a robotic surgery system (or laparoscopy) and colonoscopy, is safe and feasible for resection of stage T1 colorectal cancer and has a good short-term prognosis.

Background: The existing data on the degree of pain in patients during CT-guided percutaneous transthoracic needle biopsy (PTNB) of lung lesions are limited and the factors related to pain are unclear. In this study, we aimed to evaluate the prevalence and severity of pain reported during PTNB and to identify factors associated with increased reported pain., Methods: Patients who underwent PTNB from April 2022 to November 2022 were prospectively evaluated using the numeric rating scale, which assesses subjective pain based on a 0-10 scoring system (0 = no pain; 10 = the worst pain imaginable). The scale divides the scores into three categories: mild pain (1-3 points), moderate pain (4-6 points), and severe pain (7-10 points). Pain scores from 4 to 10 were considered significant pain. Demographic data of patients, lesion characteristics, biopsy variables, complications, the patient's subjective feelings, and pathological result data were analyzed by multivariable logistic regression analysis to identify variables associated with significant pain., Results: We enrolled 215 participants who underwent 215 biopsy procedures (mean age: 64.5 ± 9.3 years, 123 were men). The mean procedure-related pain score was 2 ± 2. Overall, 20% (43/215) of participants reported no pain (score of 0), 67.9% (146/215) reported pain scores of 1-3, 11.2% (24/215) reported scores of 4-6, and 0.9% (2/215) reported scores of 7 or higher. Furthermore, non-significant pain (scores of 0-3) was reported during 87.9% (189/215) of the procedures. In the adjusted model, significant pain was positively associated with lesions ≥ 34 mm (p = 0.001, odds ratio [OR] = 6.90; 95% confidence interval [CI]: 2.18, 21.85), a needle-pleural angle ≥ 77° (p = 0.047, OR = 2.44; 95% CI: 1.01, 5.89), and a procedure time ≥ 26.5 min (p = 0.031, OR = 3.11; 95% CI: 1.11, 8.73)., Conclusions: Most participants reported no pain or mild pain from CT-guided percutaneous transthoracic needle biopsies of lung lesions. However, those with a larger lesion, a greater needle-pleural angle, and a longer procedure time reported greater pain., (© 2023. The Author(s).)

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01&#95;AE,CRF07&#95;BC,and CRF08&#95;BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs. 1.3%; χ 2 =3.929, P =0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01&#95;AE,CRF07&#95;BC,and CRF08&#95;BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

Overexpression of the Phosphatidylinositol 3-kinase (PI3K) proteins have been observed in cancer cells. Targeting the phosphatidylinositol 3-kinase (PI3K) signaling transduction pathway by inhibition of the PI3K substrate recognition sites has been proved to be an effective approach to block cancer progression. Many PI3K inhibitors have been developed. Seven drugs have been approved by the US FDA with a mechanism of targeting the phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. In this study, we used docking tools to investigate selective binding of ligands toward four different subtypes of PI3Ks (PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ). The affinity predicted from both the Glide dock and the Movable-Type (MT)-based free energy calculations agreed well with the experimental data. The validation of our predicted methods with a large dataset of 147 ligands showed very small mean errors. We identified residues that may dictate the subtype-specific binding. Particularly, residues Asp964, Ser806, Lys890 and Thr886 of PI3Kγ might be utilized for PI3Kγ-selective inhibitor design. Residues Val828, Trp760, Glu826 and Tyr813 may be important for PI3Kδ-selective inhibitor binding., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The mode of human immunodeficiency virus (HIV) transmission via injection drug use (IDU) still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi., Methods: We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data., Results: Among the 535 subjects, CRF08&#95;BC (57.4%), CRF01&#95;AE (28.4%), and CRF07&#95;BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs., Conclusion: HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces. Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Ferroptosis is a new form of regulated cell death characterized by excessive iron accumulation and uncontrollable lipid peroxidation. The role of ferroptosis in metabolic dysfunction-associated fatty liver disease (MAFLD) is not fully elucidated. In this study we compared the therapeutic effects of ferroptosis inhibitor liproxstatin-1 (LPT1) and iron chelator deferiprone (DFP) in MAFLD mouse models. This model was established in mice by feeding a high-fat diet with 30% fructose in water (HFHF) for 16 weeks. The mice then received LPT1 (10 mg·kg -1 ·d -1 , ip) or DFP (100 mg·kg -1 ·d -1 , ig) for another 2 weeks. We showed that both LPT1 and DFP treatment blocked the ferroptosis markers ACSL4 and ALOX15 in MAFLD mice. Furthermore, LPT1 treatment significantly reduced the liver levels of triglycerides and cholesterol, lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), and ameliorated the expression of lipid synthesis/oxidation genes (Pparα, Scd1, Fasn, Hmgcr and Cpt1a), insulin resistance, mitochondrial ROS content and liver fibrosis. Importantly, LPT1 treatment potently inhibited hepatic apoptosis (Bax/Bcl-xL ratio and TUNEL + cell number), pyroptosis (cleavages of Caspase-1 and GSDMD) and necroptosis (phosphorylation of MLKL). Moreover, LPT1 treatment markedly inhibited cleavages of PANoptosis-related caspase-8 and caspase-6 in MAFLD mouse liver. In an in vitro MAFLD model, treatment with LPT1 (100 nM) prevented cultured hepatocyte against cell death induced by pro-PANoptosis molecules (TNF-α, LPS and nigericin) upon lipid stress. On the contrary, DFP treatment only mildly attenuated hepatic inflammation but failed to alleviate lipid deposition, insulin resistance, apoptosis, pyroptosis and necroptosis in MAFLD mice. We conclude that ferroptosis inhibitor LPT1 protects against steatosis and steatohepatitis in MAFLD mice, which may involve regulation of PANoptosis, a coordinated cell death pathway that involves apoptosis, pyroptosis and necroptosis. These results suggest a potential link between ferroptosis and PANoptosis., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Role of DNA damage and demethylation on anticancer activity of DNA methyltransferase inhibitors (DNMTi) remains undefined. We report the effects of DNMT1 gene deletion/disruption (DNMT1 -/- ) on anticancer activity of a class of DNMTi in vitro, in vivo and in human cancers. The gene deletion markedly attenuated cytotoxicity and growth inhibition mediated by decitabine, azacitidine and 5-aza-4'-thio-2'-deoxycytidine (aza-T-dCyd) in colon and breast cancer cells. The drugs induced DNA damage that concurred with DNMT1 inhibition, subsequent G 2 /M cell-cycle arrest and apoptosis, and upregulated p21 in DNMT1 +/+  versus DNMT1 -/- status, with aza-T-dCyd the most potent. Tumor growth and DNMT1 were significantly inhibited, and p21 was upmodulated in mice bearing HCT116 DNMT1 +/+  xenograft and bladder PDX tumors. DNMT1 gene deletion occurred in ~ 9% human colon cancers and other cancer types at varying degrees. Decitabine and azacitidine demethylated CDKN2A/CDKN2B genes in DNMT1 +/+  and DNMT1 -/- conditions and increased histone-H3 acetylation with re-expression of p16 INK4A /p15 INK4B in DNMT1 -/- state. Thus, DNMT1 deletion confers resistance to DNMTi, and their anti-cancer activity is determined by DNA damage effects. Patients with DNMT1 gene deletions may not respond to DNMTi treatment., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Endophytic fungi from desert plants belong to a unique microbial community that has been scarcely investigated chemically and could be a new resource for bioactive natural products. In this study, 13 secondary metabolites ( 1-13 ) with diverse carbon skeletons, including a novel polyketide (1) with a unique 5,6-dihydro-4 H ,7 H -2,6-methanopyrano[4,3- d ][1,3]dioxocin-7-one ring system and three undescribed polyketides ( 2 , 7 , and 11 ), were obtained from the endophytic fungus Neocamarosporium betae isolated from two desert plant species. Different approaches, including HR-ESI-MS, UV spectroscopy, IR spectroscopy, NMR, and CD, were used to determine the planar and absolute configurations of the compounds. The possible biosynthetic pathways were proposed based on the structural characteristics of compounds 1-13 . Compounds 1 , 3 , 4 , and 9 exhibited strong cytotoxicity toward HepG2 cells compared with the positive control. Several metabolites ( 2 , 4-5 , 7-9 , and 11-13 ) were phytotoxic to foxtail leaves. The results support the hypothesis that endophytic fungi from special environments, such as desert areas, produce novel bioactive secondary metabolites., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Tan, Yang, Wang, Li, Sun, Xing, Sun, Yang and Ding.)

In this article, an extended state observer (ESO) design problem is investigated for uncertain nonlinear systems subject to limited network bandwidth. First, for rational information exchange scheduling, a dynamic event-triggered (DET) communication protocol is proposed. Different from the traditional static event-triggered strategies with fixed thresholds, an internal dynamic variable is introduced to be adaptively adjusted by a dual-directional regulating mechanism. Thus, more desirable tradeoff between observation performance and communication resource efficiency is achieved. Second, inspired by our early work on Takagi-Sugeno fuzzy ESO (TSFESO), a novel paradigm of event-triggered TSFESO is initially proposed. Third, under the DET mechanism, the TSFESO design approach is derived to carry out exponential convergence for estimation error dynamics. Finally, the effectiveness of the proposed method is verified by numerical examples. The nonlinear estimating efficiency and linear numerical tractability are integrated in TSFESO. In addition, a generalized ESO formulation is developed to allow some nonadditive uncertainties incompatible with total disturbance, such as improved event-triggered strategy, and thus, the application sphere of ESO is further expanded.

Motion control is critical in mobile robot systems, which determines the reliability and accuracy of a robot. Due to model uncertainties and widespread external disturbances, a simple control strategy cannot match tracking accuracy with disturbance immunity, while a complex controller will consume excessive energy. For precise motion control with disturbance immunity and low energy consumption, a control method based on an enhanced reduced-order extended state observer (ERESOBC) is proposed to control the motor-wheels dynamic model of a differential driven mobile robot (DDMR). In this method, only unknown state error and negative disturbance are estimated by the enhanced reduced-order extended state observer (ERESO), which reduces the required energy of the observer. In addition, a simple state-feedback-feedforward controller is used to track the reference signal and compensate for negative disturbance. Through numerical simulation and application example, the tracking performance and disturbance rejection performance of DDMR are compared with the traditional control method based on enhanced extended state observer (EESOBC), and the results show the superiority of the ERESOBC method.

The images acquired by a single visible light sensor are very susceptible to light conditions, weather changes, and other factors, while the images acquired by a single infrared light sensor generally have poor resolution, low contrast, low signal-to-noise ratio, and blurred visual effects. The fusion of visible and infrared light can avoid the disadvantages of two single sensors and, in fusing the advantages of both sensors, significantly improve the quality of the images. The fusion of infrared and visible images is widely used in agriculture, industry, medicine, and other fields. In this study, firstly, the architecture of mainstream infrared and visible image fusion technology and application was reviewed; secondly, the application status in robot vision, medical imaging, agricultural remote sensing, and industrial defect detection fields was discussed; thirdly, the evaluation indicators of the main image fusion methods were combined into the subjective evaluation and the objective evaluation, the properties of current mainstream technologies were then specifically analyzed and compared, and the outlook for image fusion was assessed; finally, infrared and visible image fusion was summarized. The results show that the definition and efficiency of the fused infrared and visible image had been improved significantly. However, there were still some problems, such as the poor accuracy of the fused image, and irretrievably lost pixels. There is a need to improve the adaptive design of the traditional algorithm parameters, to combine the innovation of the fusion algorithm and the optimization of the neural network, so as to further improve the image fusion accuracy, reduce noise interference, and improve the real-time performance of the algorithm.

Plastid genome and nuclear ribosomal DNA (nrDNA) arrays, proposed recently as "super-barcodes," might provide additional discriminatory power and overcome the limitations of traditional barcoding loci, yet super-barcodes need to be tested for their effectiveness in more plant groups. Morphological homoplasy among Schima species makes the genus a model for testing the efficacy of super-barcodes. In this study, we generated multiple data sets comprising standard DNA barcodes (matK, rbcL, trnH-psbA, nrITS) and super-barcodes (plastid genome, nrDNA arrays) across 58 individuals from 12 out of 13 species of Schima from China. No samples were correctly assigned to species using standard DNA barcodes and nrDNA arrays, while only 27.27% of species with multiple accessions were distinguished using the plastid genome and its partitioned data sets-the lowest estimated rate of super-barcode success in the literature so far. For Schima and other taxa with similarly recently divergence and low levels of genetic variation, incomplete lineage sorting, hybridization or taxonomic oversplitting are all possible causes of the failure. Taken together, our study suggests that by no means are super-barcodes immune to the challenges imposed by evolutionary complexity. We therefore call for developing multilocus nuclear markers for species discrimination in plant groups., (© 2022 John Wiley & Sons Ltd.)

Tuberculosis (TB) is one of the world's deadliest infectious disease killers today, and despite China's increasing efforts to prevent and control TB, the TB epidemic is still very serious. In the context of the COVID-19 pandemic, if reliable forecasts of TB epidemic trends can be made, they can help policymakers with early warning and contribute to the prevention and control of TB. In this study, we collected monthly reports of pulmonary tuberculosis (PTB) in Guiyang, China, from January 1, 2010 to December 31, 2020, and monthly meteorological data for the same period, and used LASSO regression to screen four meteorological factors that had an influence on the monthly reports of PTB in Guiyang, including sunshine hours, relative humidity, average atmospheric pressure, and annual highest temperature, of which relative humidity (6-month lag) and average atmospheric pressure (7-month lag) have a lagging effect with the number of TB reports in Guiyang. Based on these data, we constructed ARIMA, Holt-Winters (additive and multiplicative), ARIMAX (with meteorological factors), LSTM, and multivariable LSTM (with meteorological factors). We found that the addition of meteorological factors significantly improved the performance of the time series prediction model, which, after comprehensive consideration, included the ARIMAX (1,1,1) (0,1,2) 12 model with a lag of 7 months at the average atmospheric pressure, outperforms the other models in terms of both fit (RMSE = 37.570, MAPE = 10.164%, MAE = 28.511) and forecast sensitivity (RMSE = 20.724, MAPE = 6.901%, MAE = 17.306), so the ARIMAX (1,1,1) (0,1,2) 12 model with a lag of 7 months can be used as a predictor tool for predicting the number of monthly reports of PTB in Guiyang, China., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2022 Sheng-xiong Yang et al.)

The fungus Emericella sp. XL029 isolated from leaves of Panax notoginseng was investigated for agents with potential antibacterial and antifungal activities using a one strain-many compounds (OSMAC) strategy. Fifteen compounds, including seven undescribed structures, were obtained from this species. Their structures were confirmed by extensive spectroscopic data, single-crystal X-ray crystallography and quantum chemistry calculations. Emerlactam A exhibited better antibacterial activity against multidrug-resistant Enterococcus faecium and antifungal activity against Helminthosporium maydis, with an MIC value of 12.5 μg/mL. Quiannulatic acid displayed significant antibacterial activity against multidrug-resistant Enterococcus faecium and multidrug-resistant Enterococcus faecalis with MIC values of 1.56 μg/mL and 3.13 μg/mL, respectively. 5-alkenylresorcinol exhibited significant antifungal activity against all tested phytopathogenic fungi with MIC values ranging from 6.25 to 12.5 μg/mL., (Copyright © 2022 Elsevier Ltd. All rights reserved.)