Semantic-oriented Visual Prompt Learning for Diabetic Retinopathy Grading on Fundus Images.

Diabetic retinopathy (DR) is a serious ocular condition that requires effective monitoring and treatment by ophthalmologists. However, constructing a reliable DR grading model remains a challenging and costly task, heavily reliant on high-quality training sets and adequate hardware resources. In this paper, we investigate the knowledge transferability of large-scale pre-trained models (LPMs) to fundus images based on prompt learning to construct a DR grading model efficiently. Unlike full-tuning which fine-tunes all parameters of LPMs, prompt learning only involves a minimal number of additional learnable parameters while achieving a competitive effect as full-tuning. Inspired by visual prompt tuning, we propose Semantic-oriented Visual Prompt Learning (SVPL) to enhance the semantic perception ability for better extracting task-specific knowledge from LPMs, without any additional annotations. Specifically, SVPL assigns a group of learnable prompts for each DR level to fit the complex pathological manifestations and then aligns each prompt group to task-specific semantic space via a contrastive group alignment (CGA) module. We also propose a plug-and-play adapter module, Hierarchical Semantic Delivery (HSD), which allows the semantic transition of prompt groups from shallow to deep layers to facilitate efficient knowledge mining and model convergence. Our extensive experiments on three public DR grading datasets demonstrate that SVPL achieves superior results compared to other transfer tuning and DR grading methods. Further analysis suggests that the generalized knowledge from LPMs is advantageous for constructing the DR grading model on fundus images.

Peripheral nerve-derived Sema3A promotes osteogenic differentiation of mesenchymal stem cells through the Wnt/ß-catenin/Nrp1 positive feedback loop.

Sensory nerves play a crucial role in maintaining bone homeostasis by releasing Semaphorin 3A (Sema3A). However, the specific mechanism of Sema3A in regulation of bone marrow mesenchymal stem cells (BMMSCs) during bone remodelling remains unclear. The tibial denervation model was used and the denervated tibia exhibited significantly lower mass as compared to sham operated bones. In vitro, BMMSCs cocultured with dorsal root ganglion cells (DRGs) or stimulated by Sema3A could promote osteogenic differentiation through the Wnt/ß-catenin/Nrp1 positive feedback loop, and the enhancement of osteogenic activity could be inhibited by SM345431 (Sema3A-specific inhibitor). In addition, Sema3A-stimulated BMMSCs or intravenous injection of Sema3A could promote new bone formation in vivo. To sum up, the coregulation of bone remodelling is due to the ageing of BMMSCs and increased osteoclast activity. Furthermore, the sensory neurotransmitter Sema3A promotes osteogenic differentiation of BMMSCs via Wnt/ß-catenin/Nrp1 positive feedback loop, thus promoting osteogenesis in vivo and in vitro.

Diverse Data Generation for Retinal Layer Segmentation with Potential Structure Modelling.

Accurate retinal layer segmentation on optical coherence tomography (OCT) images is hampered by the challenges of collecting OCT images with diverse pathological characterization and balanced distribution. Current generative models can produce high-realistic images and corresponding labels without quantitative limitations by fitting distributions of real collected data. Nevertheless, the diversity of their generated data is still limited due to the inherent imbalance of training data. To address these issues, we propose an image-label pair generation framework that generates diverse and balanced potential data from imbalanced real samples. Specifically, the framework first generates diverse layer masks, and then generates plausible OCT images corresponding to these layer masks using two customized diffusion probabilistic models respectively. To learn from imbalanced data and facilitate balanced generation, we introduce pathological-related conditions to guide the generation processes. To enhance the diversity of the generated image-label pairs, we propose a potential structure modeling technique that transfers the knowledge of diverse sub-structures from lowly- or non-pathological samples to highly pathological samples. We conducted extensive experiments on two public datasets for retinal layer segmentation. Firstly, our method generates OCT images with higher image quality and diversity compared to other generative methods. Furthermore, based on the extensive training with the generated OCT images, downstream retinal layer segmentation tasks demonstrate improved results. The code is publicly available at: https://github.com/nicetomeetu21/GenPSM.

Linking bacterial life strategies with the distribution pattern of antibiotic resistance genes in soil aggregates after straw addition.

Straw addition markedly affects the soil aggregates and microbial community structure. However, its influence on the profile of antibiotic resistance genes (ARGs), which are likely associated with changes in bacterial life strategies, remains unclear. To clarify this issue, a soil microcosm experiment was incubated under aerobic (WS) or anaerobic (AnWS) conditions after straw addition, and metagenomic sequencing was used to characterise ARGs and bacterial communities in soil aggregates. The results showed that straw addition shifted the bacterial life strategies from K- to r-strategists in all aggregates, and the aerobic and anaerobic conditions stimulated the growth of aerobic and anaerobic r-strategist bacteria, respectively. The WS decreased the relative abundances of dominant ARGs such as QnrS5, whereas the AnWS increased their abundance. After straw addition, the macroaggregates consistently exhibited a higher number of significantly altered bacteria and ARGs than the silt+clay fractions. Network analysis revealed that the WS increased the number of aerobic r-strategist bacterial nodes and fostered more interactions between r-and K-strategist bacteria, thus promoting ARGs prevalence, whereas AnWS exhibited an opposite trend. These findings provide a new perspective for understanding the fate of ARGs and their controlling factors in soil ecosystems after straw addition. ENVIRONMENTAL IMPLICATIONS: Straw soil amendment has been recommended to mitigate soil fertility degradation, improve soil structure, and ultimately increase crop yields. However, our findings highlight the importance of the elevated prevalence of ARGs associated with r-strategist bacteria in macroaggregates following the addition of organic matter, particularly fresh substrates. In addition, when assessing the environmental risk posed by ARGs in soil that receives crop straw, it is essential to account for the soil moisture content. This is because the species of r-strategist bacteria that thrive under aerobic and anaerobic conditions play a dominant role in the dissemination and accumulation of ARG.

Five new eremophilane-type sesquiterpenes from the fresh roots of Rehmannia glutinosa.

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.

Anti-inflammatory monomeric sorbicillinoids from the marine-fish-derived fungus Trichoderma sp. G13.

Four new monomeric sorbicillinoids, trichillinoids A - D (1-4), along with two known dimeric sorbicillinoids (5 and 6), and five known monomeric sorbicillinoids (7-11), were obtained from the marine-fish-derived fungus Trichoderma sp. G13. They were structurally characterized on the basis of comprehensive spectroscopic investigations (NMR, HRESIMS, and ECD). Compounds 1-4 displayed moderate anti-inflammatory activities, according to inhibiting the production of NO in RAW264.7 cells activated with IC50 values ranging from 14 to 20 µM.

Protective Effect of Resveratrol Combined with Levodopa Against Oxidative Damage in Dopaminergic Neurons.

Levodopa (L-3,4-dihydroxyphenylalanine, L-Dopa) alleviates the symptoms of Parkinson's disease (PD), yet prolonged usage may give rise to severe adverse effects. Resveratrol (RSV) is a potent antioxidant, anticancer and anti-inflammatory agent. And a variety of polyphenol antioxidant compounds derived from RSV combined with levodopa have demonstrated neuroprotective activity against neuronal cell death. The purpose of this study was to examine the impact of this combination of RSV and L-Dopa on the survival rate, growth status, and reactive oxygen species (ROS) of MES23.5 dopamine (DA) neuron cells. In this study, we induced MPP+ in MES23.5 dopamine neuron cells and observed their survival rate, growth status, ROS content, as well as the effect of RSV combined with L-Dopa on cell survival. We also measured malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels as indicators of mitochondrial function, oxidative stress, and oxidative damage in the cells. Our results indicated that the MES23.5 dopamine neurons had decreased survival, poor growth status, and increased ROS content after MPP+ induction. Moreover, we found that MDA levels were elevated, and SOD activity levels were decreased, suggesting that the cells experienced abnormal mitochondrial function. However, when RSV was combined with L-Dopa, the cells showed a reduced level of MPP + -induced oxidative damage, with a more significant inhibitory effect observed in the RSV group at a concentration of 50 µmol/L. In conclusion, we found that the effects of co-administration of RSV with L-Dopa (100 µmol/L) was more effective than L-Dopa administered at the high dose. Thus, we found that RSV has the potential to reduce the dose of L-Dopa required to improve PD symptoms.

Liver kinase B-1 modulates the activity of dopamine neurons in the ventral tegmental area and regulates social memory formation.

Social memory is the ability to discriminate between familiar and unknown conspecifics. It is an important component of social cognition and is therefore essential for the establishment of social relationships. Although the neural circuit mechanisms underlying social memory encoding have been well investigated, little focus has been placed on the regulatory mechanisms of social memory processing. The dopaminergic system, originating from the midbrain ventral tegmental area (VTA), is a key modulator of cognitive function. This study aimed to illustrate its role in modulating social memory and explore the possible molecular mechanisms. Here, we show that the activation of VTA dopamine (DA) neurons is required for the formation, but not the retrieval, of social memory. Inhibition of VTA DA neurons before social interaction, but not 24 h after social interaction, significantly impaired social discrimination the following day. In addition, we showed that the activation of VTA DA neurons was regulated by the serine/threonine protein kinase liver kinase B1 (Lkb1). Deletion of Lkb1 in VTA DA neurons reduced the frequency of burst firing of dopaminergic neurons. Furthermore, Lkb1 plays an important role in regulating social behaviors. Both genetic and virus-mediated deletions of Lkb1 in the VTA of adult mice impaired social memory and subsequently attenuated social familiarization. Altogether, our results provide direct evidence linking social memory formation to the activation of VTA DA neurons in mice and illustrate the crucial role of Lkb1 in regulating VTA DA neuron function.

Intensity-dependent effects of tDCS on motor learning are related to dopamine.

Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), are popular methods for inducing neuroplastic changes to alter cognition and behaviour. One challenge for the field is to optimise stimulation protocols to maximise benefits. For this to happen, we need a better understanding of how stimulation modulates cortical functioning/behaviour. To date, there is increasing evidence for a dose-response relationship between tDCS and brain excitability, however how this relates to behaviour is not well understood. Even less is known about the neurochemical mechanisms which may drive the dose-response relationship between stimulation intensities and behaviour. Here, we examine the effect of three different tDCS stimulation intensities (1 mA, 2 mA, 4 mA anodal motor cortex tDCS) administered during the explicit learning of motor sequences. Further, to assess the role of dopamine in the dose-response relationship between tDCS intensities and behaviour, we examined how pharmacologically increasing dopamine availability, via 100 mg of levodopa, modulated the effect of stimulation on learning. In the absence of levodopa, we found that 4 mA tDCS improved and 1 mA tDCS impaired acquisition of motor sequences relative to sham stimulation. Conversely, levodopa reversed the beneficial effect of 4 mA tDCS. This effect of levodopa was no longer evident at the 48-h follow-up, consistent with previous work characterising the persistence of neuroplastic changes in the motor cortex resulting from combining levodopa with tDCS. These results provide the first direct evidence for a role of dopamine in the intensity-dependent effects of tDCS on behaviour.

[Effect of Biochar on NO3--N Transport in Loessial Soil and Its Simulation].

The objective of this study was to explore the effects of different amounts of biochar on the migration process and characteristics of NO3--N in loessial soil. In this study, six groups of mixed soil samples with biochar and loessial soil mass ratios of 0% (T0), 1% (T1), 2% (T2), 3% (T3), 4% (T4), and 5% (T5) were used as research objects. NO3--N was used as the tracer. Through the indoor soil column solute transport simulation tests, the effects of different biochar application amounts on the NO3--N transport process in loessial soil were simulated and studied. The results showed that the breakthrough curve of NO3--N in loessial soil shifted to the right with the increasing of biochar application, and the peak value gradually decreased. The initial penetration time, complete penetration time, and total penetration time increased with the increasing of biochar application amount. The total penetration time of NO3- in the T1, T2, T3, T4, and T5 treatments was 1.26, 2.31, 2.72, 3.22, and 3.57 times that of T0, respectively. The R2 was > 0.997 and RMSE was < 2.083 of the two-zone model (TRM). Compared with the convection-dispersion equation (CDE), the TRM model had higher fitting accuracy and could better simulate the NO3--N migration process in loessial soil after the application of different contents of biochar. The analysis of the fitting parameters of the TRM model showed that the average pore velocity, hydrodynamic dispersion coefficient, and water content ratio in the movable zone gradually decreased with the increasing of biochar application, whereas the dispersion and mass exchange coefficient showed an increasing trend. The results showed that biochar application could effectively enhance the ability of loessial soil to fix NO3--N, reduce the leakage of NO3--N to groundwater, and play an important role in maintaining soil fertility and preventing groundwater pollution.

The relationship between childhood maltreatment subtypes and adolescent internalizing problems: The mediating role of maladaptive cognitive emotion regulation strategies.

BACKGROUND: While childhood maltreatment is understood to be a significant risk factor for adolescent internalizing problems (depression and anxiety), underlying mechanisms linking each type of maltreatment to internalizing problems in adolescents remain unclear. Moreover, the current state of knowledge regarding the associations between maladaptive cognitive emotion regulation strategies and each type of maltreatment, as well as their impact on adolescent internalizing problems, is limited. Additionally, it remains unclear whether these maladaptive strategies mediate this relationship. OBJECTIVE: This study sought to investigate the effects of childhood maltreatment types on adolescent internalizing problems and to explore whether the overall and specific types of maladaptive strategies mediate these associations. METHODS: Using a cross-sectional design, adolescents (N = 7071, Mage = 14.05 years, SDage = 1.54) completed online questionnaires assessing childhood maltreatment, maladaptive cognitive emotion regulation strategies (including rumination, catastrophizing, self-blame, and other-blame), anxiety, and depression. The hypothesized mediating effects were tested using the Lavaan package in R software (4.1.2). RESULTS: Different maltreatment types had varying effects on adolescent internalizing problems. Emotional neglect, emotional abuse, and sexual abuse significantly affected anxiety and depression, whereas physical neglect and physical abuse did not. Other than physical neglect and physical abuse, overall maladaptive strategies mediated the relationship between the other three types of maltreatment (emotional abuse, emotional neglect, and sexual abuse) and internalizing problems (anxiety and depression). For specific maladaptive strategies, rumination mediated the effects of physical abuse, emotional abuse, emotional neglect, and sexual abuse on internalizing problems (anxiety and depression). In contrast, catastrophizing mediated the relationship between physical neglect, emotional abuse, emotional neglect, sexual abuse and internalizing problems (anxiety and depression). CONCLUSIONS: These results suggest that the effects of maltreatment types on internalizing problems are different and that maladaptive strategies, particularly rumination and catastrophizing, are important mechanisms through which childhood maltreatment affects internalizing problems. This is a reminder that mental health workers need to consider the different effects of maltreatment types when intervening and recognize the importance of prioritizing interventions for rumination and catastrophizing.

Genome-wide identification of ZmMYC2 binding sites and target genes in maize.

BACKGROUND: Jasmonate (JA) is the important phytohormone to regulate plant growth and adaption to stress signals. MYC2, an bHLH transcription factor, is the master regulator of JA signaling. Although MYC2 in maize has been identified, its function remains to be clarified. RESULTS: To understand the function and regulatory mechanism of MYC2 in maize, the joint analysis of DAP-seq and RNA-seq is conducted to identify the binding sites and target genes of ZmMYC2. A total of 3183 genes are detected both in DAP-seq and RNA-seq data, potentially as the directly regulating genes of ZmMYC2. These genes are involved in various biological processes including plant growth and stress response. Besides the classic cis-elements like the G-box and E-box that are bound by MYC2, some new motifs are also revealed to be recognized by ZmMYC2, such as nGCATGCAnn, AAAAAAAA, CACGTGCGTGCG. The binding sites of many ZmMYC2 regulating genes are identified by IGV-sRNA. CONCLUSIONS: All together, abundant target genes of ZmMYC2 are characterized with their binding sites, providing the basis to construct the regulatory network of ZmMYC2 and better understanding for JA signaling in maize.

Changes of soil nutrients and organic carbon fractions in Caragana korshinskii forests with different restoration years in mountainous areas of southern Ningxia, China.

Vegetation restoration can effectively enhance soil quality and soil organic carbon (SOC) sequestration. In this study, the distribution characteristics of soil nutrients and SOC along soil profile (0-100 cm), and their responses to restoration years (16, 28, 38 years) were studied in Caragana korshinskii plantations in the southern mountainous area of Ningxia, compared with cropland and natural grassland. The results showed that: 1) the contents of SOC, soil total nitrogen (TN), total phosphorus (TP), particulate organic carbon (POC), mineral-associated organic carbon (MAOC) and the proportion of particulate organic carbon to total organic carbon (POC/SOC) all decreased with increasing soil depth. The ratio of mineral-associated organic carbon to total organic carbon (MAOC/SOC) exhibited an opposite trend. 2) The contents of SOC, TN, TP, C:P, N:P, POC and MAOC gra-dually decreased as the restoration years increased. However, the C:N ratio showed no significant change. The POC/SOC ratio initially increased and then decreased, while the MAOC/SOC ratio decreased initially and then increased. 3) In three different types of vegetation, POC, MAOC, and SOC showed a highly significant positive linear correlation, with the increase in SOC mainly depended on the increase in MAOC. The SOC, TN, TP, POC and MAOC contents in natural grassland and C. korshinskii plantations were significantly higher than those in cropland. In conclusion, soil nutrients and POC and MAOC contents of C. korshinskii plantations gradually decreased with the increases in restoration years. However, when compared with cropland, natural grassland and C. korshinskii plantations demonstrated a greater capacity to maintain and enhance soil nutrient and carbon storage.

Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate. METHODS: A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone. RESULTS: After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC. CONCLUSION: Collectively, these findings suggest that domperidone serves as an effective "multi-target" inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

Virtual reality exergames for improving physical function, cognition and depression among older nursing home residents: A systematic review and meta-analysis.

OBJECTIVE: To explore the effectiveness of virtual reality (VR) exergames on physical function, cognition and depression among older nursing home residents. METHODS: A systematic review and meta-analysis were conducted. The PubMed, Ovid, Embase, Cochrane, CINAHL, and Web of Science databases were searched for relevant studies from inception until June 1, 2023. The reviewers independently completed the study selection, data extraction and quality assessment. Subgroup analyses were conducted to explore the sources of between-study heterogeneity and to determine whether participant or intervention characteristics influenced effect sizes. RESULTS: Eighteen studies met the inclusion criteria and were selected for qualitative and quantitative synthesis. The overall methodological quality was relatively high, and the overall evidence grade was moderate. VR exergames had a large effect on physical function, including mobility [SMD=-0.66, P < 0.001], balance [SMD=0.95, P < 0.001], and lower limb strength [SMD=0.53, P = 0.0009]; and a moderate effect on cognition [SMD=0.48, P = 0.02] and depression [SMD=-0.72, P = 0.03]. Subgroup analyses revealed that a training frequency of 2 sessions per week and coordinating with physiotherapists yielded greater improvements in mobility (P = 0.009; P = 0.0001). VR exergames had especially beneficial effects on balance for physically fit participants (P = 0.03) and on cognition for participants with cognitive impairment (P = 0.01). Additionally, regarding the improvement of depression, commercial VR exergames were superior to self-made systems (P = 0.03). CONCLUSION: VR exergames can provide a positive impact on physical function, cognition and depression among older nursing home residents. The study also demonstrated the different benefits of exergames between participants who were physically fit and those with cognitive impairment, which is considered as an innovative, cost-efficient and sustainable approach. Specifically, commercial VR exergame programs with a frequency of 2 sessions per week and coordinating with physiotherapists may be the most appropriate and effective option.

[Distribution characteristics of microbial necromass carbon along soil profiles in different restoration periods of Caragana korshinskii in mountainous areas of Southern Ningxia, China]. / å®å—å±±åŒºä¸åŒæ¢å¤å¹´é™æŸ æ¡æž—åœ°åœŸå£¤å¾®ç”Ÿç‰©æ®‹ä½“ç¢³æ²¿å‰–é¢åˆ†å¸ƒç‰¹å¾.

Microbial necromass, an important and stable source of soil organic carbon (SOC), is an important index to evaluate the contribution of microorganisms to SOC transformation and accumulation. It is not clear about the accumulation of microbial necromass in deep soil layer and its contribution to SOC during the restoration process of Caragana korshinskii forests. Combined with the biomarker method, we investigated the carbon contents of bacte-rial, fungal, and microbial necromass in the soil profiles (0-100 cm) of C. korshinskii forests in 16, 28, and 38 years of restoration, with natural grassland as control. We further examined the contribution of microbial necromass to soil organic carbon. The results showed that: 1) Along the soil profile (0-100 cm), the contents of fungal necromass carbon (FNC), bacterial necromass carbon (BNC), and microbial necromass carbon (MNC) significantly decreased with increasing soil depth in natural grassland and C. korshinskii forests. Except for the significant decrease in FNC/SOC, BNC/SOC, and MNC/SOC in the soil of C. korshinskii forests in 38 years of restoration, FNC/SOC and MNC/SOC generally showed an increasing trend followed by a decreasing trend in other plots, while BNC/SOC gradually decreased. 2) With the increases of restoration years, the contents of FNC, BNC, and MNC significantly decreased in C. korshinskii forests. FNC/SOC and MNC/SOC showed an overall increasing trend followed by a decreasing trend, while BNC/SOC gradually decreased. 3) The average contribution of microbial necromass carbon to SOC was highest in C. korshinskii forests in 28 years of restoration (35.0%), followed by C. korshinskii forests in 16 years of restoration (33.5%), natural grassland (31.0%), and C. korshinskii forests in 38 years of restoration (28.6%). In conclusion, when the restoration years of C. korshinskii forests are 16, the contents of microbial necromass carbon and their contributions to SOC are higher compared to natural grassland, which are beneficial for SOC sequestration.

"Loop-Neurorrhaphy Technique for Preventing Bone Resorption and Preserving Lower Lip Sensation in Mandibular Reconstruction using Vascularized Iliac Bone Flap: A Single-Center Randomized Clinical Trial".

BACKGROUND: The aim of this study was to investigate whether using an innervated vascularized iliac bone flap could effectively prevent bone resorption and maintain sensory function in the lower lip. METHODS: In the innervated group, the deep circumflex iliac artery and recipient vessels were anastomosed, with simultaneous microanastomosis of ilioinguinal nerve, mental nerve and inferior alveolar nerve. Conversely, the control group underwent solely vascular anastomosis. CT was utilized to assess bone quality. Sensory recovery of the lower lip was recorded using two-point discrimination and current perception threshold testing. RESULTS: The study comprised a total of 40 subjects, with each group accounting for 20 participants, equally distributed in terms of gender. Hounsfield unit loss was significantly lower in the innervated group (13.26±8.65 %) as compared to the control group (37.98±8.60 %) (P < 0.001). Moreover, two-point discrimination values were lower in the innervated group (15.11±8.39 mm) when compared to the control group (21.44±7.24 mm) (P = 0.02). The current perception threshold values for the innervated group were 176.19 ± 31.89, 64.21 ± 19.23, and 42.29 ± 18.96 in 2kHz, 250Hz, and 5Hz respectively, while in the control group, the current perception threshold values were 204.47 ± 36.99, 82.26 ± 27.29, and 58.89 ± 25.38 in 2kHz, 250Hz, and 5Hz (P =0.02, 0.02, and 0.03, respectively). CONCLUSIONS: The innervated vascularized iliac bone flap represents a safe and effective novel approach to preserving lower lip sensation and preventing bone resorption through functional mandibular reconstruction.

Efficient O- and S-glycosylation with ortho-2,2-dimethoxycarbonylcyclopropylbenzyl thioglycoside donors by catalytic strain-release.

We herein present a strain-release glycosylation method employing a rationally designed ortho-2,2-dimethoxycarbonylcyclopropylbenzyl (CCPB) thioglycoside donor. The donor is activated through the nucleophilic ring-opening of a remotely activable donor-acceptor cyclopropane (DAC) catalyzed by mild Sc(OTf)3. Our new glycosylation method efficiently synthesizes O-, N-, and S-glycosides, providing facile chemical access to the challenging S-glycosides. Because the activation conditions of conventional glycosyl donors and our CCPB thioglycoside are orthogonal, our novel donor is amenable to controlled one-pot glycosylation reactions with conventional donors for expeditious access to complex glycans. The strain-release glycosylation is applied to the assembly of a tetrasaccharide of O-polysaccharide of Escherichia coli O-33 in one pot and the synthesis of a 1,1'-S-linked glycoside oral galectin-3 (Gal-3) inhibitor, TD139, to demonstrate the versatility and effectiveness of the novel method for constructing both O- and S-glycosides.

The Role of Metabolomics and Microbiology in Urinary Tract Infection.

One of the common illnesses that affect women's physical and mental health is urinary tract infection (UTI). The disappointing results of empirical anti-infective treatment and the lengthy time required for urine bacterial culture are two issues. Antibiotic misuse is common, especially in females who experience recurrent UTI (rUTI). This leads to a higher prevalence of antibiotic resistance in the microorganisms that cause the infection. Antibiotic therapy will face major challenges in the future, prompting clinicians to update their practices. New testing techniques are making the potential association between the urogenital microbiota and UTIs increasingly apparent. Monitoring changes in female urinary tract (UT) microbiota, as well as metabolites, may be useful in exploring newer preventive treatments for UTIs. This review focuses on advances in urogenital microbiology and organismal metabolites relevant to the identification and handling of UTIs in an attempt to provide novel methods for the identification and management of infections of the UT. Particular attention is paid to the microbiota and metabolites in the patient's urine in relation to their role in supporting host health.