Deciphering the Roles of Extracellular Polymeric Substances (EPS) in Shaping Disinfection Kinetics through Permanent Removal via Genetic Disruption.

Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.

4-Hydroxyphenylpyruvate Dioxygenase-Like predicts the prognosis and the immunotherapy response of cancers: a pan-cancer analysis.

The 4-Hydroxyphenylpyruvate Dioxygenase-Like (HPDL) protein plays a crucial role in safeguarding cells from oxidative stress by orchestrating metabolic reprogramming. New research suggests that HPDL is considerably increased in pancreatic ductal adenocarcinoma, although its impact on cancer immunotherapy is still unclear. Pancancer transcriptional data were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression datasets. The cBioPortal webtool was utilized to examine genomic changes in different cancer types. The prognostic significance of HPDL in pancancer was evaluated using univariate Cox regression analysis. Extensive utilization of the CTRP and PRISM databases was performed to forecast potential medications that specifically target HPDL in LUAD. In summary, studies were conducted to evaluate the impact of HPDL on the proliferation and movement of LUAD cells using loss-of-function experiments. HPDL is expressed excessively in a wide variety of cancer types, indicating its prognostic and predictive value. Moreover, we emphasized the strong correlation between HPDL and indicators of immune stimulation, infiltration of immune cells, and expression of immunoregulators. The remarkable finding of the HPDL was its capacity to precisely anticipate responses to cancer therapies using anti-PDL1 and anti-PD1 antibodies among individuals. Moreover, HPDL can function as a predictive marker for specific inhibitors in instances of cancer. Suppression of HPDL resulted in reduced growth and movement of LUAD cells. To summarize, our results suggest that HPDL acts as a prospective predictor of outcomes and a positive indication of response to immunotherapy in patients undergoing treatment with immune checkpoint inhibitors (ICIs).

Network-based analysis identifies potential therapeutic ingredients of Chinese medicines and their mechanisms toward lung cancer.

Lung cancer is one of the most common malignant tumors around the world, which has the highest mortality rate among all cancers. Traditional Chinese medicine (TCM) has attracted increased attention in the field of lung cancer treatment. However, the abundance of ingredients in Chinese medicines presents a challenge in identifying promising ingredient candidates and exploring their mechanisms for lung cancer treatment. In this work, two network-based algorithms were combined to calculate the network relationships between ingredient targets and lung cancer targets in the human interactome. Based on the enrichment analysis of the constructed disease module, key targets of lung cancer were identified. In addition, molecular docking and enrichment analysis of the overlapping targets between lung cancer and ingredients were performed to investigate the potential mechanisms of ingredient candidates against lung cancer. Ten potential ingredients against lung cancer were identified and they may have similar effect on the development of lung cancer. The results obtained from this study offered valuable insights and provided potential avenues for the development of novel drugs aimed at treating lung cancer.

Taking spontaneous plants as a natural strategy for vegetation restoration in construction and demolition waste landfills: a case study in Suzhou, China.

Construction and demolition waste (CDW) landfills around the city have caused serious damage to the ecological environment and menaced the public health. Restoration of closed CDW landfills is critical to compensate for the degraded ecosystem and ensure safety in further development and utilization. Vegetation restoration is an essential part of the restoration of CDW landfills, in which the use of spontaneous plants is the foundation of the nature-based strategy. In this study, Fenghuangshan CDW landfill in Suzhou, China, was selected as the research site, and the species composition and diversity of the spontaneous plants were analyzed. Moreover, the types of habitats and growth indexes of 8 species with high frequency and 18 species with medium frequency in the CDW landfill were investigated, and a comprehensive evaluation of growth rate and expansion capacity of the 26 species was conducted. The results showed that, herbs were the main type of the spontaneous plants in the CDW landfill. The species and quantities of the spontaneous plants in the CDW landfill were obviously fewer than those in the surrounding areas of the CDW landfill, and the Shannon-Wiener index and Pielou index of the spontaneous plants were lower compared with the surrounding areas of the CDW landfill. Meanwhile, the differences of dominant families and the distribution of origins, life forms and growth types between these two fields were insignificant. The heliophilous and drought tolerance species were widely distributed in the CDW landfill while the shade-tolerant or hygrophilous species were few. The relatively large comprehensive evaluation indexes of Elymus dahuricus, Daucus carota, Sonchus asper, Geranium carolinianum, Rumex acetosa, Metaplexis japonica, Carex breviculmis, Erigeron canadensis, Trigonotis peduncularis, Lamium amplexicaule reflected their high growth rates and strong expansion capacity, demonstrating their great potentiality in the vegetation restoration of CDW landfills as indispensable components of the nature-based solution.

First Reports of Cladosporium tenuissimum Causing Leaf spots on Hydrangea macrophylla in Anhui province in China.

Forever Summer Hydrangea (Hydrangea macrophylla) is a common flowering plant in the Yangtze River Valley area of China, and it is widely cultivated globally (Chen et al. 2015). In July 2023, H. macrophylla leaves exhibiting visible diseased lesions were reported in a nursery in Wuhu, Anhui Province, China. The incidence reached 40% in a 0.2 ha area. The primary disease symptom was multiple irregular necrotic spots (0.5 to 1 mm in diameter) appearing on the leaves. These spots on the leaves were faded yellow around the perimeter and grayish brown in the center.). 15 leaf samples were sterilized with 75% alcohol and rinsed three times in sterile distilled water, then transferred to antibiotic-added potato dextrose agar (PDA) for incubation at 27°C. The colonies were fluffy, flocculent, or hairy, dark green, gray-green to gray-brown in color, and spreading or protruding punctate with a colorless halo on PDA. The conidiophores were brown to dark brown, smooth or rough surface, mostly unbranched, clearly differentiated, erect or curved. The conidia displayed a light brown to brown hue, lemon shape, fusiform, elongated ellipsoid or others with obvious spore markings and spore umbilicus. Genomic DNA was extracted from fungal colonies on infected leaves of three collections separately (Braun et al. 2003) and the internal transcribed spacer regions (ITS), actin (ACT) genes and partial translation elongation factor-l-alpha (EF) were amplified and sequenced using the primers ITS1/4 (Yin et al. 2012), ACT-512F/ACT-783R and EF 1-728F/986R (Carbone and Kohn 1999), respectively. DNA sequences of isolates were identical and deposited in GenBank (accession no. OR362754 for ITS, OR611929 for ACT and PP209106 for EF). The consensus sequences from ITS, EF and ACT showed 100%, 98.98% and 100% identical to Cladosporium strains (accession no. OQ186140.1, MT154169.1 and OL322092.1), respectively. To confirm the pathogenicity of the isolates, hydrangeas were planted in 15-cm pots containing commercial potting mix (one plant/pot). Three healthy plants were inoculated at the five to eight leaf stage by spraying 50 µL of the isolate conidial suspension (4 × 106 spores/mL) on healthy leaves. Three plants treated with sterile distilled water were used as controls. After inoculation, all plants were placed in a humidity chamber (>95% relative humidity, 26°C) for 48 h and then transferred to a greenhouse at 22/27°C. All inoculated leaves exhibited symptoms similar to those observed in the nursery 10 days after inoculation, while no symptoms were observed for control leaves. The fungus was re-isolated and confirmed to be C. tenuissimum. Based on the above morphological characterization and molecular identification, the causal agent for this leaf spot disease was identified as C. tenuissimum. Although C. tenuissimum has been reported to cause disease on H. paniculata in northern China (Li et al.2021), this is the first time that C. tenuissimum has been found on H. macrophylla in southern China. This new disease of H. macrophylla caused by C. tenuissimum is a threat to urban greening and is worth further investigation.

Use of municipal solid waste incineration (MSWI) bottom ash as a permeable subgrade material: An experimental and mechanism study.

As a traditional method of waste treatment, municipal solid waste incineration (MSWI) has become one of the main methods of urban waste treatment. However, as a byproduct of MSWI, a large amount of MSWI bottom ash is not reused in current practice. This study innovatively posits MSWI bottom ash as an eco-friendly adsorbent rather than a pollutant, exploring its potential application as a permeable subgrade material. The results reveal that MSWI bottom ash exhibits promising properties to serve as a permeable subgrade material to achieve the permeability and improve the sustainability for subgrade. Due to the arrangement of its particles, it shows excellent performance in shear strength and permeability, which are comparable to or surpass those of sandy soils. The average pore width of 14.200 nm allows heavy metal substances to be encapsulated within the matrix, significantly reducing their leachability, thereby aligning with environmental friendliness standards. Its adsorption capacity is about 6.60 mg/g, and the adsorption capacity per volume is 3.66 times and 2.04 times that of fly ash and clay, respectively. The mechanism analysis shows that the adsorption process is monolayer heterogeneous adsorption. This paper presents a novel perspective on reusing MSWI bottom ash and provides evidence supporting its effective utilization as a permeable subgrade material, offering substantial environmental benefits through enhanced adsorption ability.Implications: Municipal solid waste incineration (MSWI) is a common method for municipal solid waste treatment, while the MSWI bottom ash is often not reused. This paper explored the explores the feasibility of using MSWI bottom ash as a permeable road base material. The results show that the particle arrangement enables excellent shear strength and permeability, comparable to sandy soil. It meets safety requirements for the leaching of heavy metals and acts as an adsorbent for pollutants leaching from permeable pavements. Furthermore, the mechanisms underlying these behaviors of MSWI were confirmed by microstructural and mineralogical analyses. These indicate that MSWI bottom ash has great potential as a permeable road base material. This paper provides a clear understanding of the physical, mechanical and environmental properties of MSWI bottom ash, which can promote its reuse in practice.

Effects of exercise, metformin, and combination treatments on type 2 diabetic mellitus-induced muscle atrophy in db/db mice: Crosstalk between autophagy and the proteasome

Both exercise and metformin are common effective clinical treatments of type 2 diabetic mellitus. This study investigated the functional role of exercise, metformin, and combination treatment on type 2 diabetic mellitus–induced muscle atrophy. In this experiment, a total of 10 BKS mice were set as the control group. A total of 40 BKS-db/db mice were randomly divided into the control group (db/db); the exercise intervention group (db/db + Ex), which ran on a treadmill at 7–12 m/min, 30–40 min/day, 5 days/week; the metformin administration group (db/db + Met), which was administered 300 mg/kg of metformin solution by gavage daily; and the exercise combined with metformin administration group (db/db + Ex + Met). After 8 weeks of intervention, their tibialis anterior muscles were removed. The levels of insulin signaling pathway proteins, ubiquitin proteasome, and autophagic lysosome–associated proteins were detected using western blot, the expression of MuRF1 and Atrogin-1 was detected using immunohistochemical staining, and the degradation of autophagosomes was detected using double-labeled immunofluorescence. The db/db mice exhibited reduced insulin sensitivity and inhibition of the autophagic–lysosome system, the ubiquitin–proteasome system was activated, and protein degradation was exacerbated, leading to skeletal muscle atrophy. Exercise and metformin and their combined interventions can increase insulin sensitivity, whereas exercise alone showed more effective in inhibiting the ubiquitin–proteasome system, improving autophagy levels, and alleviating skeletal muscle atrophy. Compared with metformin, exercise demonstrated superior improvement of muscle atrophy by promoting the synthesis and degradation of autophagy through the AMPK/ULK1 pathway. However, the combination treatment exhibits no synergistic effect on muscle atrophy. (AU)

Electrophile-Controlled Regiodivergent Palladium-Catalyzed Imidoylative Spirocyclization of Cyclic Alkenes.

An intermolecular controllable Pd-catalyzed spirocyclization of isocyano cycloalkenes has been developed, offering efficient and selective approaches toward spirocyclic hydropyrrole scaffolds. 2-Azaspiro-1,7-dienes could be obtained through a "chain-walking" process with aryl/vinyl iodides as electrophiles, while the normal Heck product 2-azaspiro-1,6-dienes were selectively generated when aryl triflates were used as the coupling partner of isocyanides. Mechanistic studies suggested that the counteranion of the Pd(II) intermediate played a crucial role in the regioselectivity control. Dihydropyrrole-fused 5,6,7-membered spirocycles were switchably accessed under mild conditions with wide functional group tolerance.

Potential mechanisms of exercise for relieving inflammatory pain: a literature review of animal studies.

Inflammatory pain (IP) is one of the most prevalent and intractable human conditions, and it leads to progressive dysfunction and reduced quality of life. Additionally, IP is incredibly challenging to treat successfully with drugs or surgery. The development of IP is complex and multifactorial, and peripheral and central sensitization may influence chronicity and treatment resistance in IP. Understanding the mechanisms underlying IP is vital for developing novel therapies. Strong evidence suggests that exercise can be a first-line relief for patients with IP during rehabilitation. However, the mechanisms through which exercise improves IP remain unclear. Here, we reviewed the current animal experimental evidence for an exercise intervention in IP and proposed biological mechanisms for the effects of synaptic plasticity in the anterior cingulate cortex, endocannabinoids, spinal dorsal horn excitability balance, immune cell polarization balance, cytokines, and glial cells. This information will contribute to basic science and strengthen the scientific basis for exercise therapy prescriptions for IP in clinical practice.

Effects of exercise, metformin, and combination treatments on type 2 diabetic mellitus-induced muscle atrophy in db/db mice: Crosstalk between autophagy and the proteasome

Both exercise and metformin are common effective clinical treatments of type 2 diabetic mellitus. This study investigated the functional role of exercise, metformin, and combination treatment on type 2 diabetic mellitus–induced muscle atrophy. In this experiment, a total of 10 BKS mice were set as the control group. A total of 40 BKS-db/db mice were randomly divided into the control group (db/db); the exercise intervention group (db/db + Ex), which ran on a treadmill at 7–12 m/min, 30–40 min/day, 5 days/week; the metformin administration group (db/db + Met), which was administered 300 mg/kg of metformin solution by gavage daily; and the exercise combined with metformin administration group (db/db + Ex + Met). After 8 weeks of intervention, their tibialis anterior muscles were removed. The levels of insulin signaling pathway proteins, ubiquitin proteasome, and autophagic lysosome–associated proteins were detected using western blot, the expression of MuRF1 and Atrogin-1 was detected using immunohistochemical staining, and the degradation of autophagosomes was detected using double-labeled immunofluorescence. The db/db mice exhibited reduced insulin sensitivity and inhibition of the autophagic–lysosome system, the ubiquitin–proteasome system was activated, and protein degradation was exacerbated, leading to skeletal muscle atrophy. Exercise and metformin and their combined interventions can increase insulin sensitivity, whereas exercise alone showed more effective in inhibiting the ubiquitin–proteasome system, improving autophagy levels, and alleviating skeletal muscle atrophy. Compared with metformin, exercise demonstrated superior improvement of muscle atrophy by promoting the synthesis and degradation of autophagy through the AMPK/ULK1 pathway. However, the combination treatment exhibits no synergistic effect on muscle atrophy. (AU)

Integrated multi-omics analyses reveal the TM4SF family genes with prognostic and therapeutic relevance in hepatocellular carcinoma.

TM4SF family members (TM4SFs) have been shown to be aberrantly expressed in multiple types of cancer. However, a comprehensive investigation of the TM4SFs has yet to be performed in LIHC. The study comprehensively investigated the expression and prognostic value of TM4SFs. Then, a TM4SFs-based risk model and nomogram were constructed for prognostic prediction. Finally, functional loss of TM4SFs was performed to verify the potential role of TM4SFs in LIHC. We found that TM4SFs were significantly up-regulated in LIHC. High expression and hypomethylation of TM4SFs were associated with poor prognosis of LIHC patients. Then, a TM4SFs-based risk model was constructed that could effectively classify LIHC patients into high and low-risk groups. In addition, we constructed a prognostic nomogram that could predict the long-term survival of LIHC patients. Based on immune infiltration analysis, high-risk patients had a relatively higher immune status than low-risk patients. Moreover, the prediction module could predict patient responses to immunotherapy and chemotherapy. Finally, loss-of-function studies showed that TM4SF4 knockdown could substantially suppress the growth, migratory, and invasive abilities of LIHC cells. Targeting TM4SFs will contribute to effective immunotherapy strategies and improve the prognosis of liver cancer patients.

Study on the Cooling Performance of a Focused Ultrasonic Radiator for Electrical Heating Elements.

In this work, a focused ultrasonic radiator is proposed for cooling the electrical heating elements in the focal region, and its working characteristics are investigated. The analyses of the FEM computational and flow field visualization test results indicate that focused ultrasound can generate forced convective heat transfer by the acoustic streaming in the focal region, which can cool the heating elements effectively. Experiments show that when the input voltage is 30Vp-p and the ambient temperature is 25 °C, the focused ultrasonic radiator can cause the surface temperature of the heating element (high-temperature alumina ceramic heating plate with a diameter of 5 mm) in the focal region to drop from 100 °C to about 55 °C. When the diameter of the electrical heating element is changed from 5 mm to 30 mm, the cooling effect is similar in the focal region. Compared with a fan, the focused ultrasound radiator has a shorter cooling time and a more concentrated cooling area. The focused ultrasonic radiator proposed in this work is suitable for some special environments.

Downhill running and caloric restriction attenuate insulin resistance associated skeletal muscle atrophy via the promotion of M2-like macrophages through TRIB3-AKT pathway.

BACKGROUD: Downhill running has recently become a promising exercise modality for metabolic syndrome, but the effect and precise mechanism of downhill running training on insulin resistance (IR) induced skeletal muscle atrophy remains unclear. The current study aimed to explore the benefits of downhill running training accompanied by a low-fat diet on skeletal muscle atrophy in IR mice and its possible mechanisms. METHODS: For in vivo study, high fat diet (HFD) -induced IR mice were submitted to the downhill running training or/and caloric restriction for 8 weeks. In vitro study was performed using co-cultured RAW264.7 macrophages and C2C12 myoblasts model. Glucose tolerance test (GTT), insulin tolerance test (ITT), immunofluorescence staining, Western blot analysis, hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), Cell counting kit-8 (CCK-8) assays and glucose uptake assays were employed to explore the benefits and possible mechanisms of downhill running training accompanied by a low-fat diet on IR mice. RESULTS: Our data revealed that HFD induces IR, which leading to skeletal muscle atrophy. Downhill running accompanied by caloric restriction mitigated HFD-induced IR and improve skeletal muscle atrophy. Further study suggested that descended TRIB3 mediated the favorable impact of downhill running on IR induced skeletal muscle atrophy by suppressing M1-like macrophages and promoting M2-like macrophages. Macrophages-specific knockdown of TRIB3 exerted similar effects on the macrophage polarization and IR related myogenesis to downhill running training accompanied by caloric restriction. In contrast, macrophages-specific overexpression of TRIB3 descended phosphorylation of AKT, further activated M1-like macrophages and aggravated IR related inhibition of myogenesis. CONCLUSIONS: This finding demonstrated the beneficial effects of downhill running training and caloric restriction on IR related skeletal muscle atrophy by promoting M2-like macrophages through TRIB3-AKT pathway.

Recipient site scalp necrosis: A rare postoperative complication of hair transplantation.

BACKGROUND: Recipient area scalp necrosis is considered a potential complication of hair transplantation, but has rarely been reported. A small number of patients have developed scalp necrosis after hair transplantation with the widely used Follicular unit excision (FUE) technique. There are no guidelines to prevent and manage this complication. The aim of this study was to provide an insight into the pathogenesis, prevention, and management of scalp necrosis following hair transplantation. METHODS: From 2012 to 2021, among more than 10 000 patients who underwent hair transplantation, only three developed scalp necrosis in our clinical experience, besides, one patient transferred to our hospital because of scalp necrosis after undergoing hair transplantation. According to the disease etiology and patients' symptom, a combination of wound management and antimicrobial therapy was employed. This study was approved by the institutional ethics committee of Nanfang Hospital. RESULTS: Of the four patients, three received timely treatment and had a good prognosis. Necrosis became confined and healed within 2-3 weeks. Grafts in the lesion area partially survived. In case 4, due to improper treatment at the early stage, the lesion developed extensively and deeply, which not only delayed wound healing, but also resulted in complete loss of grafts. CONCLUSION: Preoperative prophylaxis, timely diagnosis, and immediate treatment of scalp necrosis can prevent serious complications and reduce morbidity after hair transplantation.

MulCNN-HSP: A multi-scale convolutional neural networks-based deep learning method for classification of heat shock proteins.

Heat shock proteins (HSPs) are crucial cellular stress proteins that react to environmental cues, ensuring the preservation of cellular functions. They also play pivotal roles in orchestrating the immune response and participating in processes associated with cancer. Consequently, the classification of HSPs holds immense significance in enhancing our understanding of their biological functions and in various diseases. However, the use of computational methods for identifying and classifying HSPs still faces challenges related to accuracy and interpretability. In this study, we introduced MulCNN-HSP, a novel deep learning model based on multi-scale convolutional neural networks, for identifying and classifying of HSPs. Comparative results showed that MulCNN-HSP outperforms or matches existing models in the identification and classification of HSPs. Furthermore, MulCNN-HSP can extract and analyze essential features for the prediction task, enhancing its interpretability. To facilitate its accessibility, we have made MulCNN-HSP available at http://cbcb.cdutcm.edu.cn/HSP/. We hope that MulCNN-HSP will contribute to advancing the study of HSPs and their roles in various biological processes and diseases.

Effects of exercise, metformin, and combination treatments on type 2 diabetic mellitus-induced muscle atrophy in db/db mice: Crosstalk between autophagy and the proteasome.

Both exercise and metformin are common effective clinical treatments of type 2 diabetic mellitus. This study investigated the functional role of exercise, metformin, and combination treatment on type 2 diabetic mellitus-induced muscle atrophy. In this experiment, a total of 10 BKS mice were set as the control group. A total of 40 BKS-db/db mice were randomly divided into the control group (db/db); the exercise intervention group (db/db + Ex), which ran on a treadmill at 7-12 m/min, 30-40 min/day, 5 days/week; the metformin administration group (db/db + Met), which was administered 300 mg/kg of metformin solution by gavage daily; and the exercise combined with metformin administration group (db/db + Ex + Met). After 8 weeks of intervention, their tibialis anterior muscles were removed. The levels of insulin signaling pathway proteins, ubiquitin proteasome, and autophagic lysosome-associated proteins were detected using western blot, the expression of MuRF1 and Atrogin-1 was detected using immunohistochemical staining, and the degradation of autophagosomes was detected using double-labeled immunofluorescence. The db/db mice exhibited reduced insulin sensitivity and inhibition of the autophagic-lysosome system, the ubiquitin-proteasome system was activated, and protein degradation was exacerbated, leading to skeletal muscle atrophy. Exercise and metformin and their combined interventions can increase insulin sensitivity, whereas exercise alone showed more effective in inhibiting the ubiquitin-proteasome system, improving autophagy levels, and alleviating skeletal muscle atrophy. Compared with metformin, exercise demonstrated superior improvement of muscle atrophy by promoting the synthesis and degradation of autophagy through the AMPK/ULK1 pathway. However, the combination treatment exhibits no synergistic effect on muscle atrophy.

Electroacupuncture for acute transverse myelitis following viral infection: A case report.

BACKGROUND: Electroacupuncture (EA) has a positive effect on neurological repair and functional recovery following spinal cord disease. However, evidence of its effectiveness in acute transverse myelitis (ATM) cases is limited. PATIENT PRESENTATION: A 48-year-old woman experienced headache and fever for 5 days, followed by a sudden onset of back pain, lower limb paralysis, and urinary and bowel dysfunction. The patient received intravenous medications. However, she did not experience improvement in clinical symptoms. She subsequently underwent acupuncture treatment. She regained walking ability and experienced improved bladder function and bowel control after 36 sessions of EA treatment. METHODS: CARE guidelines informed the case study report. The MRC and ICIQ-UI-SF scores were used to verify changes in lower-extremity muscle strength and urination after EA treatment. Qualitative information was collected using feedback tables. CONCLUSION: Pharmacological treatment for ATM lacks clear advantages because of its complex pathophysiological mechanisms. Hence, EA could be recommended as a promising treatment modality for ATM.

Unveiling the mechanisms of nephrotoxicity caused by nephrotoxic compounds using toxicological network analysis.

Billions of people worldwide have experienced irreversible kidney injuries, which is mainly attributed to the complexity of drug-induced nephrotoxicity. Consequently, there is an urgent need for uncovering the mechanisms of nephrotoxicity caused by compounds. In the present study, a network-based methodology was applied to explore the mechanisms of nephrotoxicity induced by specific compounds. Initially, a total of 42 nephrotoxic compounds and 60 kinds of syndromes associated with nephrotoxicity were collected from public resources. Afterward, network localization and separation algorithms were used to map the targets of compounds and diseases into the human interactome. By doing so, 199 statistically significant nephrotoxic networks displaying the interaction between compound targets and disease genes were obtained, which played pivotal roles in compounds-induced nephrotoxicity. Subsequently, enrichment analysis pinpointed core Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways that highlight commonalities in nephrotoxicity induced by nephrotoxic compounds. It was found that nephrotoxic compounds primarily induce nephrotoxicity by mediating the advanced glycosylation end products-receptor for advanced glycosylation end products signaling pathway in diabetic complications, human cytomegalovirus infection, lipid and atherosclerosis, Kaposi sarcoma-associated herpesvirus infection, apoptosis, and the phosphatidylinositol 3-kinase-Akt pathways. These results provide valuable insights for preventing drug-induced nephrotoxicity. Furthermore, the approaches we used are also helpful in conducting research on other kinds of toxicities.

Synthesis of arene-functionalized fused heterocyclic scaffolds via a regioselective cascade 1,4-conjugate addition/5-exo-dig annulation strategy.

Facile access to furan fused heterocyclic scaffolds through a regioselective cascade reaction of propargylamines with 4-hydroxy-2H-pyran-2-ones and 4-hydroxy-6-methylpyridin-2(1H)-one has been achieved. This cascade reaction presumably involves the formation of ortho-alkynyl quinone methide (o-AQM), 1,4-conjugate addition, followed by regioselective 5-exo-dig annulation, and a 1,3-H shift process. Moreover, the reaction provides a new and efficient method for the synthesis of highly sterically congested 3-phenolic furo[3,2-c]pyran-4-ones and furo[3,2-c]pyridin-4(5H)-ones by the formation of a furan ring from readily available starting materials in good to high yields (50-82%) with broad functional group compatibility in a single step. Significantly, the strategy described here is easily scalable and several useful synthetic transformations of the prepared arene-functionalized 4H-furo[3,2-c]pyran-4-ones were also performed.