Compare the Quadriceps Activity between Mini-Midvastus and Mini-Medial Parapatellar Approach in Total Knee Arthroplasty with Electromyography.

Background: The comparison between the mini-midvastus (mini-MV) and mini-parapatellar (mini-MPP) approach in total knee arthroplasty (TKA) remains a subject of debate. The present study compared quadriceps activation, pain levels, and clinical outcomes between the two approaches; quadricep activation was assessed using surface electromyography (sEMG). Methods: This retrospective cross-sectional study comprised a total of 78 patients aged between 50 and 85 years with primary osteoarthritis. Patients were divided into a mini-MV (n = 38) group and a mini-MPP (n = 40) group according to the surgical approach. Results: The two groups exhibited no significant differences in sEMG for the vastus medialis (VM) or rectus femoris (RF) at the follow-up time points, with the exception that the mini-MV group exhibited superior strength of RF during extensions at the 2-week follow-up. However, the mini-MPP group had superior Western Ontario and McMaster Universities Index (WOMAC) total and function scores at the 2- and 6-week follow-ups. The mini-MPP group also had superior WOMAC stiffness scores at the 2-week follow-up. The two groups did not differ significantly in terms of pain levels or morphine consumption. Conclusions: The sEMG data of quadriceps muscle would not differ significantly between the mini-MV and mini-MPP approaches for TKA. Moreover, the mini-MPP approach may yield superior WOMAC scores when compared with the mini-MV approach.

Artificial intelligence-empowered collection and characterization of microplastics: A review.

Microplastics have been detected from water and soil systems extensively, with increasing evidence indicating their detrimental impacts on human and animal health. Concerns surrounding microplastic pollution have spurred the development of advanced collection and characterization methods for studying the size, abundance, distribution, chemical composition, and environmental impacts. This paper offers a comprehensive review of artificial intelligence (AI)-empowered technologies for the collection and characterization of microplastics. A framework is presented to streamline efforts in utilizing emerging robotics and machine learning technologies for collecting, processing, and characterizing microplastics. The review encompasses a range of AI technologies, delineating their principles, strengths, limitations, representative applications, and technology readiness levels, facilitating the selection of suitable AI technologies for mitigating microplastic pollution. New opportunities for future research and development on integrating robots and machine learning technologies are discussed to facilitate future efforts for mitigating microplastic pollution and advancing AI technologies.

Association between pain and cognitive and daily functional impairment in older institutional residents: a cross-sectional study.

BACKGROUND: Pain is often neglected in disabled older population, especially in Taiwan where the population of institutional residents is rapidly growing. Our study aimed to investigate pain prevalence and associated factors among institutional residents to improve pain assessment and management. METHODS: This nationwide study recruited 5,746 institutional residents in Taiwan between July 2019 and February 2020. Patient self-report was considered the most valid and reliable indicator of pain. A 5-point verbal rating scale was used to measure pain intensity, with a score ranging from 2 to 5 indicating the presence of pain. Associated factors with pain, including comorbidities, functional dependence, and quality of life, were also assessed. RESULTS: The mean age of the residents was 77.1 ± 13.4 years, with 63.1% of them aged over 75 years. Overall, 40.3% of the residents reported pain, of whom 51.2% had moderate to severe pain. Pain was more common in residents with comorbidities and significantly impacted emotions and behavior problems, and the mean EQ5D score, which is a measure of health-related quality of life (p < .001). Interestingly, pain was only related to instrumental activities of daily living (IADL) and not activities of daily living (ADL). On the other hand, dementia was significantly negatively associated with pain (p < .001), with an estimated odds of 0.63 times (95% CI: 0.53-0.75) for the presence of pain when compared to residents who did not have dementia. CONCLUSIONS: Unmanaged pain is common among institutional residents and is associated with comorbidities, IADL, emotional/behavioral problems, and health-related quality of life. Older residents may have lower odds of reporting pain due to difficulty communicating their pain, even through the use of a simple 5-point verbal rating scale. Therefore, more attention and effort should be directed towards improving pain evaluation in this vulnerable population .

Expressions of miR-96-5p, miR-29b-3p, and Their Target Gene THBS1 in Clear Cell Renal Cell Carcinoma and Sunitinib Resistance.

Objective: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of RCC and comprises approximately 70% of all RCC cases, with high incidence and metastatic relapse. Sunitinib is a first-line drug for treating patients with metastatic RCC but drug resistance inevitably occurs in a vast majority of patients after 15 months of systematic treatment. Herein, we attempted to explain the possible mechanism of sunitinib resistance in ccRCC. Methods: Two expression profiles with accession numbers GSE64052 and GSE76068 in the GEO were utilized to identify differentially expressed genes (|log2FC| ≥ 1 with adjusted P < .05) between sunitinib sensitivity and sunitinib resistance in ccRCC. The study included tumor and matched non-tumor kidney tissues obtained from 64 ccRCC patients who underwent nephrectomy before adjuvant therapy. Results: The gene expression profiles of GSE64052 and GSE76068 datasets yielded 92 and 66 differentially expressed genes between sunitinib sensitivity and sunitinib resistance in ccRCC, respectively. The PPI analysis revealed CTGF, RSAD2, and THBS1 as hub genes among which only THBS1 was found to be correlated with the survival of ccRCC patients. miR-96-5p and miR-29b-3p were common miRNAs targeting THBS1 and correlated with the survival of ccRCC patients. The luciferase activity assays demonstrated THBS1 as the target gene of miR-96-5p and miR-29b-3p. Results of qRT-PCR provided evidence of higher expressions of miR-96-5p and miR-29b-3p with a lower expression of THBS1 in tumor kidney tissues than matched non-tumor kidney tissues and in tumor kidney tissues of responders than those of non-responders. More specifically, elevated expressions of miR-96-5p, miR-29b-3p, and a declined expression of THBS1 were observed in tumor samples with advanced ccRCCs and higher Fuhrman grades. Pearson correlation analysis yielded significantly negative correlations between miR-96-5p and THBS1 (P < .006, r = -0.339), between miR-29b-3p and THBS1 (P < .05, r = -0.421). Conclusion: Our study suggests that miR-96-5p- and miR-29b-3p-mediated THBS1 inhibition is associated with sunitinib resistance in ccRCC, offering a better understanding of the mechanism elucidating acquired drug resistance in ccRCC.

Multimodal Analgesia with Local Wound Infiltration and Intravenous Parecoxib for Thyroidectomy.

Background and objective: Adequate postoperative pain control is an important component to enhance recovery. Multimodal analgesia with various pain control techniques has been widely used to alleviate postoperative pain. The use of either wound infiltration or a superficial cervical plexus block has been reported to be effective for pain management after thyroid surgery. The present study evaluated the effect of multimodal analgesia using lidocaine wound infiltration combined with intravenous parecoxib for patients monitored after thyroidectomy. Materials and Methods: A total of 101 patients with a multimodal analgesia protocol being monitored after thyroidectomy were enrolled. After the induction of anesthesia, multimodal analgesia was performed through wound infiltration of 1% lidocaine and epinephrine at a ratio of 1:200,000 (5 µg/mL) combined 40 mg intravenous parecoxib before skin excision. Patients were divided into two groups for this retrospective analysis based on the injection dose of lidocaine they received. Patients in Group I (the control, n = 52) received a 5 mL injection solution, while those in Group II (the study, n = 49) received a 10 mL dosage in a time-sequential manner, in accordance with a previous clinical trial. The primary outcome was measuring postoperative pain intensity at rest, as well as during motion and coughing, which was measured at the postoperative anesthetic care unit (PACU) and on the first day after the operation (POD 1) in the ward. Pain intensity was assessed using a numerical rating scale (NRS). The secondary outcomes were postoperative adverse events including anesthetic-related side effects, as well as airway and pulmonary complications. Results: Most of the patients reported no pain or mild pain during the observation period. The patients in Group II had a lower pain intensity during motion than Group I (NRS 1.47 ± 0.89 vs. 1.85 ± 0.96, p = 0.043) when measured at the postoperative anesthetic care unit. Pain intensity during coughing was also significantly lower in the study group than in the control group (NRS 1.61 ± 0.95 vs. 1.96 ± 0.79, p = 0.049) when measured at the postoperative anesthetic care unit. There were no severe adverse events in either of the groups. Only one patient (1.9%) in Group I experienced temporary vocal palsy. Conclusions: The use of lidocaine with an equal volume of intravenous parecoxib provided comparable analgesia with minimal adverse events when monitoring thyroidectomy.

Hyperbaric Oxygen Therapy Alleviates Paclitaxel-Induced Peripheral Neuropathy Involving Suppressing TLR4-MyD88-NF-κB Signaling Pathway.

Paclitaxel (PAC) results in long-term chemotherapy-induced peripheral neuropathy (CIPN). The coexpression of transient receptor potential vanilloid 1 (TRPV1) and Toll-like receptor 4 (TLR4) in the nervous system plays an essential role in mediating CIPN. In this study, we used a TLR4 agonist (lipopolysaccharide, LPS) and a TLR4 antagonist (TAK-242) in the CIPN rat model to investigate the role of TLR4-MyD88 signaling in the antinociceptive effects of hyper-baric oxygen therapy (HBOT). All rats, except a control group, received PAC to induce CIPN. Aside from the PAC group, four residual groups were treated with either LPS or TAK-242, and two of them received an additional one-week HBOT (PAC/LPS/HBOT and PAC/TAK-242/HBOT group). Mechanical allodynia and thermal hyperalgesia were then assessed. The expressions of TRPV1, TLR4 and its downstream signaling molecule, MyD88, were investigated. The mechanical and thermal tests revealed that HBOT and TAK-242 alleviated behavioral signs of CIPN. Immunofluorescence in the spinal cord dorsal horn and dorsal root ganglion revealed that TLR4 overexpression in PAC- and PAC/LPS-treated rats was significantly downregulated after HBOT and TAK-242. Additionally, Western blots showed a significant reduction in TLR4, TRPV1, MyD88 and NF-κB. Therefore, we suggest that HBOT may alleviate CIPN by modulating the TLR4-MyD88-NF-κB pathway.

Autologous Fat Grafting in Female Genital Area Improves Sexual Function by Increasing Collagenesis, Angiogenesis, and Estrogen Receptors.

BACKGROUND: Vulvovaginal laxity, atrophic vaginitis, and orgasmic dysfunction are not only aesthetic but also sexual problems. Autologous fat grafting (AFG) facilitates tissue rejuvenation through the effects of adipose-derived stem cells; the fat grafts serve as soft-tissue filler. However, few studies have reported the clinical outcomes of patients undergoing vulvovaginal AFG. OBJECTIVES: The aim of this study was to describe a new technique, micro-autologous fat transplantation (MAFT), for AFG in the vulvovaginal area. Posttreatment histologic changes in the vaginal canal that imply improved sexual function were assessed. METHODS: This retrospective study enrolled females who underwent vulvovaginal AFG performed through MAFT between June 2017 and 2020. Assessments were based on the Female Sexual Function Index (FSFI) questionnaire and on histologic and immunohistochemical staining. RESULTS: In total, 20 female patients (mean age, 38.1 years) were included. On average, 21.9 mL of fat was injected into the vagina and 20.8 mL in the vulva and mons pubis area. Six months afterwards, the patients' mean total FSFI score (68.6) was significantly higher than that at baseline (43.8; P < .001). Histologic and immunohistochemical staining of vaginal tissues revealed substantially increased levels of neocollagenesis, neoangiogenesis, and estrogen receptors. By contrast, the level of protein gene product 9.5, which is associated with neuropathic pain, was considerably lower after AFG. CONCLUSIONS: AFG performed through MAFT in the vulvovaginal area may help manage sexual function-related problems in females. In addition, this technique improves aesthetics, restores tissue volume, alleviates dyspareunia with lubrication, and reduces scar tissue pain.

Spinal Irisin Gene Delivery Attenuates Burn Injury-Induced Muscle Atrophy by Promoting Axonal Myelination and Innervation of Neuromuscular Junctions.

Muscle loss and weakness after a burn injury are typically the consequences of neuronal dysregulation and metabolic change. Hypermetabolism has been noted to cause muscle atrophy. However, the mechanism underlying the development of burn-induced motor neuropathy and its contribution to muscle atrophy warrant elucidation. Current therapeutic interventions for burn-induced motor neuropathy demonstrate moderate efficacy and have side effects, which limit their usage. We previously used a third-degree burn injury rodent model and found that irisin-an exercise-induced myokine-exerts a protective effect against burn injury-induced sensory and motor neuropathy by attenuating neuronal damage in the spinal cord. In the current study, spinal irisin gene delivery was noted to attenuate burn injury-induced sciatic nerve demyelination and reduction of neuromuscular junction innervation. Spinal overexpression of irisin leads to myelination rehabilitation and muscular innervation through the modulation of brain-derived neurotrophic factor and glial-cell-line-derived neurotrophic factor expression along the sciatic nerve to the muscle tissues and thereby modulates the Akt/mTOR pathway and metabolic derangement and prevents muscle atrophy.

A comparison between cisatracurium and rocuronium-induced neuromuscular block on laryngeal electromyography recovery after neostigmine reversal in a porcine model.

Background: Inducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium. Methods: Twelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value. Results: Neostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P<0.01) and group R (16.5[2.5] vs. 26.5 [1.5] min, P<0.05) compared to spontaneous recovery, respectively. Neostigmine reversal also enhanced the maximum degree of EMG amplitude recovery in both group C (83.6 [5.1] vs. 47.2 [6.1] %, P<0.01) and group R (85.6 [18.2]vs. 57.1 [6.3] %, P<0.05) compared to spontaneous recovery, respectively. The reversal effect of neostigmine did not differ significantly between cisatracurium and rocuronium. Conclusions: This porcine model demonstrated that neostigmine provides an adequate and timely IONM signal suppressed by both cisatracurium and rocuronium. These results can potentially expand the options for precision neuromuscular block management during IONM to improve vocal outcomes in thyroid surgery patients.

Freezing solute atoms in nanograined aluminum alloys via high-density vacancies.

Low-temperature decomposition of supersaturated solid solution into unfavorable intergranular precipitates is a long-standing bottleneck limiting the practical applications of nanograined aluminum alloys that are prepared by severe plastic deformation. Minimizing the vacancy concentration is generally regarded as an effective approach in suppressing the decomposition process. Here we report a counterintuitive strategy to stabilize supersaturated solid solution in nanograined Al-Cu alloys via high-density vacancies in combination with Sc microalloying. By generating a two orders of magnitude higher concentration of vacancies bonded in strong (Cu, Sc, vacancy)-rich atomic complexes, a high thermal stability is achieved in an Al-Cu-Sc alloy that precipitation is nearly suppressed up to ~230 °C. The solute-vacancy complexes also enable the nanograined Al-Cu alloys with higher strength, greater strain hardening capability and ductility. These findings provide perspectives towards the great potentials of solute-vacancy interaction and the development of nanograined alloys with high stability and well-performed mechanical properties.

A Surgeon-Centered Neuromuscular Block Protocol Improving Intraoperative Neuromonitoring Outcome of Thyroid Surgery.

Background: Neuromuscular blocking agents provide muscular relaxation for tracheal intubation and surgery. However, the degree of neuromuscular block may disturb neuromuscular transmission and lead to weak electromyography during intraoperative neuromonitoring. This study aimed to investigate a surgeon-friendly neuromuscular block degree titrated sugammadex protocol to maintain both intraoperative neuromonitoring quality and surgical relaxation during thyroid surgery. Methods: A total of 116 patients were enrolled into two groups and underwent elective thyroid surgery with intraoperative neuromonitoring. All patients followed a standardized intraoperative neuromonitoring protocol with continuous neuromuscular transmission monitoring and received 0.6 mg/kg rocuronium for tracheal intubation. Patients were allocated into two groups according to the degree of neuromuscular block when the anterior surface of the thyroid gland was exposed. The neuromuscular block degree was assessed by the train-of-four (TOF) count and ratio. Patients in group I received sugammadex 0.25 mg/kg for non-deep neuromuscular block degree (TOF count = 1~4). Patients in group II were administered sugammadex 0.5 mg/kg for deep neuromuscular block degree (TOF count = 0). The quality of the intraoperative neuromonitoring was measured using the V1 electromyography (EMG) amplitude. An amplitude less than 500 µV and greater than 500 µV was defined as weak and satisfactory, respectively. Results: The quality of the intraoperative neuromonitoring was not different between groups I and II (satisfactory/weak: 75/1 vs. 38/2, P = 0.14). The quality of surgical relaxation was acceptable after sugammadex injection and showed no difference between groups [55/76 (72.3%) in group I vs. 33/40 (82.5%) in group II, P = 0.23]. Conclusions: This surgeon-centered sugammadex protocol guided by neuromuscular block degree (0.5 mg/kg for deep block and 0.25 mg/kg for others) showed comparably high intraoperative neuromonitoring quality and adequate surgical relaxation. The results expanded the practicality of sugammadex for precise neuromuscular block management during monitored thyroidectomy.

Dendrocorticiopsisorientalis gen. et sp. nov. of the Punctulariaceae (Corticiales, Basidiomycota) revealed by molecular data.

Dendrocorticiopsisorientalis is presented in this study as a new genus and new species based on morphological and phylogenetic evidence. This new taxon is characterized by resupinate, smooth and membranaceous basidiomata, monomitic hyphal system with clamps, colorless dendrohyphidia, variable presence of cystidia, and ellipsoid to ovoid basidiospores measuring 5-7 × 3.2-5.2 µm. The phylogenetic analyses based on the ITS1-5.8S-ITS2 (ITS) + nuclear 28S rDNA (28S) dataset of Corticiales indicated that the new taxon is nested in Punctulariaceae, separated from other genera with strong support values. Descriptions, specimen photo, and illustrations of the new taxon are provided in this study. A morphological comparison of the four genera of Punctulariaceae is given.

Effects of Field Aging on Material Properties and Rutting Performance of Asphalt Pavement.

This study evaluates field asphalt aging based on material property changes in pavement with time, and investigates if such changes could have an impact on field rutting performance. Four projects from three different climate zones were monitored as part of the NCHRP 9-49A project at two stages: during pavement construction and two to three years after opening it to traffic. Construction information were collected, and field cores were drilled at both stages to evaluate the material properties of recovered asphalt binder and asphalt mixture. Field rut depth was also measured. In addition, pavement structure, climate and base/subgrade modulus information were also obtained. Results indicate that the asphalt mixture stiffening is caused in major part by asphalt aging. However, the effect of asphalt aging on pavement mixture property may not follow a proportional liner trend. The parameters that are most sensitive to field ageing are MSCR R3.2 and dynamic modulus. It is also found that the variables which showed a good ranking trend with the field rut depth are climate condition (relative humidity, high temperature hour, solar radiation), material properties (Hamburg rut depth, rutting resistance index, high temperature performance grade, MSCR, and dynamic modulus, base and subgrade moduli), as well as air voids.

Hyperbaric Oxygen Therapy Attenuates Burn-Induced Denervated Muscle Atrophy.

Background: Neuronal apoptosis and inflammation in the ventral horn of the spinal cord contribute to denervated muscle atrophy post-burn. Hyperbaric oxygen therapy (HBOT) exerts anti-inflammation and neuroprotection. Furthermore, hypoxia-inducible factor (HIF)-1α has been reported to promote inflammation and apoptosis. We investigated the therapeutic potential of HBOT and the role of HIF-1α post-burn. Methods: Sprague-Dawley rats were divided into three groups: a control group, an untreated burn group receiving burn and sham treatment, and a HBOT group receiving burn injury and HBOT. The burn injury was induced with 75ºC ± 5ºC at the right hindpaw. HBOT (100% oxygen at 2.5 atmosphere, 90 min/day) and sham HBOT (21% oxygen at 1 atmosphere, 90 min/day) was started on day 28 after burn injury and continued for 14 treatments (days 28-41). Incapacitance (hind limb weight bearing) testing was conducted before burn and weekly after burn. At day 42 post-burn, the gastrocnemius muscle and the spinal cord ventral horn were analyzed. Results: HBOT improved burn-induced weight bearing imbalance. At day 42 post-burn, less gastrocnemius muscle atrophy and fibrosis were noted in the HBOT group than in the untreated burn group. In the ventral horn, HBOT attenuated the neuronal apoptosis and glial activation post-burn. The increases in phosphorylated AKT/mTOR post-burn were reduced after HBOT. HBOT also inhibited HIF-1α signaling, as determined by immunofluorescence and western blot. Conclusions: HBOT reduces burn-induced neuronal apoptosis in the ventral horn, possibly through HIF-1α signaling.

The First Whole Genome Sequencing of Sanghuangporus sanghuang Provides Insights into Its Medicinal Application and Evolution.

Sanghuangporus is a medicinal macrofungal genus typified by S. sanghuang, the very species utilized in traditional Chinese medicines by Chinese ancient people. To facilitate the medicinal application of S. sanghuang, we, for the first time, perform its genome sequencing and analyses from a monokaryon strain. A 33.34 Mb genome sequence was assembled to 26 contigs, which lead to the prediction of 8278 protein-coding genes. From these genes, the potential biosynthesis pathway of sesquiterpenoids was, for the first time, identified from Sanghuangporus, besides that of triterpenoids. While polysaccharides are the main medicinal metabolites in S. sanghuang, flavonoids are especially abundant medicinal metabolites comparing with other medicinal macrofungal groups. From the genomic perspective, S. sanghuang has a tetrapolar heterothallic mating system, and has its special nutritional strategy and advantageous medicinal properties compared with S. baumii and S. vaninii. A phylogenomics analysis indicates that Sanghuangporus emerged 15.39 million years ago and S. sanghuang has a closer phylogenetic relationship with S. baumii than S. vaninii. However, S. sanghuang shares a higher region of synteny and more orthologous genes, including carbohydrate-active enzymes with S. vaninii than S. baumii. A comparative genomics analysis with S. baumii and S. vaninii indicates that species diversification within Sanghuangporus may be driven by the translocation and translocation plus inversion of genome sequences, while the expansion and contraction of gene families may contribute to the host specificity of Sanghuangporus species. In general, the genome sequence of S. sanghuang provides insights into its medicinal application and evolution.

Optimization of electromyographic endotracheal tube electrode position by UEScope for monitored thyroidectomy.

OBJECTIVE: Proper position of an electromyographic (EMG) endotracheal tube within the larynx plays a key role in functional electrophysiologic intraoperative neural monitoring (IONM) in thyroid surgery. The purpose of this study was to determine the feasibility of a portable video-assisted intubation device (UEScope) to verify the optimal placement of an EMG tube. METHODS: A retrospective study enrolled 40 consecutive patients who underwent monitored thyroidectomies. After positioning the patient for surgery, an anesthesiologist performed tracheal intubation with UEScope and checked the position of the tube at the proper depth without rotation to the vocal cords. The main outcome measured was the proper EMG tube position, free from further adjustment. The secondary outcomes assessed were the percentage of available initial vagal stimulation (V1) signals. RESULTS: All tracheal intubations were successful at first attempt. Proper EMG tube placement without position adjustment was found in 97.5% of the patients. Tube withdrawal was required in a male patient. All patients obtained detectable V1 signals; the lowest and median V1 amplitude was 485 and 767 µV as a reference value, respectively. CONCLUSION: The UEScope is a valuable and reliable tool for placing an EMG tube and confirming its position during monitored thyroidectomy. In addition, further tube adjustment might be waived in most cases when the anesthesiologist placed the EMG tube after patient positioning for surgery. Routine use of video-assisted intubation devices is highly recommended. LEVEL OF EVIDENCE: 4.

Sesquiterpenes and polyphenols with glucose-uptake stimulatory and antioxidant activities from the medicinal mushroom Sanghuangporus sanghuang.

A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites (1-14) including eight sesquiterpenoids (1-8) and six polyphenols (9-14). Compounds 1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy, high resolution mass spectrometry (HRMS) and electronic circular dichroism (ECD) data. All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells, and cellular antioxidant activity. Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus (SARS-CoV-2) activity. As a result, compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%, 62.7%, 33.7% and 21.4% at the dose of 50 µmol·L-1, respectively. Compounds 9-12 also showed good cellular antioxidant activities with CAA50 values of 12.23, 23.11, 5.31 and 16.04 µmol·L-1, respectively. Molecular docking between COVID-19 Mpro and compounds 9-12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds. This work provides new insights for the potential role of the medicinal mushroom S. sanghuang as drugs and functional foods.

Sanghuangporus sanghuang Mycelium Prevents Paracetamol-Induced Hepatotoxicity through Regulating the MAPK/NF-κB, Keap1/Nrf2/HO-1, TLR4/PI3K/Akt, and CaMKKß/LKB1/AMPK Pathways and Suppressing Oxidative Stress and Inflammation.

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase ß (CaMKKß), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

Simultaneous hyperbaric oxygen therapy during systemic chemotherapy reverses chemotherapy-induced peripheral neuropathy by inhibiting TLR4 and TRPV1 activation in the central and peripheral nervous system.

BACKGROUND AND OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) is considered one of the most common sequelae in patients with cancer who experience consistent abnormal sensations or pain symptoms during or after paclitaxel (PAC) chemotherapy. Transient receptor potential vanilloid 1 (TRPV1) and toll-like receptor 4 (TLR4) have been reported to interact in the nervous system in patients with CIPN. The antinociceptive effects of hyperbaric oxygen therapy (HBOT) on CIPN was demonstrated in this study through behavior tests. Using a CIPN rat model, we examined the effects of simultaneous HBOT (SHBOT) administration during chemotherapy and discovered that SHBOT achieved better reversal effects than chemotherapy alone. MATERIALS AND METHODS: Twenty-four rats were randomly allocated to four groups: control, PAC, SHBOT, and HBOT after PAC groups. Behavior tests were performed to evaluate mechanical allodynia and thermal hyperalgesia status. Tissues from the spinal cord and dorsal root ganglions were collected, and TLR4 and TRPV1 expression and microglial activation were investigated through immunofluorescence (IF) staining. RESULTS: The mechanical and thermal behavior tests revealed that HBOT intervention during PAC treatment led to the early alleviation of CIPN symptoms and inhibited CIPN deterioration. IF staining revealed that TLR4, TRPV1, and microglial activation were all upregulated in PAC-injected rats and exhibited early and significant downregulation in SHBOT-treated rats. CONCLUSION: This study is the first to demonstrate that the use of SHBOT during PAC treatment has potential for the early suppression of CIPN initiation and deterioration, indicating that it can alleviate CIPN symptoms and may reverse CIPN in patients undergoing systemic chemotherapy.

Synergic Effect of Botulinum Toxin Type A and Triamcinolone Alleviates Scar Pruritus by Modulating Epidermal Hyperinnervation: A Preliminary Report.

BACKGROUND: Patients often experience scar-related pruritus, which adversely affects quality of life. Triamcinolone acetonide (TAC) is widely used to treat pathologic scars, and botulinum toxin type A (BTX-A) reportedly improves scarring and associated discomfort. OBJECTIVES: The aim of this study was to investigate the clinical efficacy of combining TAC and BTX-A to reduce scar itch; potential mechanisms were investigated via an animal model. METHODS: For the clinical study, each scar on a patient was divided into 2 equal parts, with one part receiving TAC/BTX-A and the other TAC alone. Therapeutic interventions were administered over 3 sessions at 4-week intervals. Itch intensity was measured on a visual analog scale before each therapeutic intervention (V1, V2, V3) and 4 weeks after the last intervention (V4). For the animal model, rats were allocated into 5 groups: control, untreated burn, TAC, BTX-A, and TAC/BTX-A. We evaluated alloknesis in the right hind paw and analyzed possible molecular mechanisms. RESULTS: In humans, TAC/BTX-A significantly reduced scar itch compared with TAC alone at V4 (P = 0.04). In rats, post-burn itch was mitigated at 4 weeks after treatment with TAC, BTX-A, and TAC/BTX-A (P = 0.03, P = 0.0054, and P = 0.0053, respectively). TAC/BTX-A significantly decreased the density of intraepidermal nerve fibers post-burn relative to the untreated burn (P = 0.0008). TAC/BTX-A downregulated the expressions of nerve growth factor and protein transient receptor potential vanilloid subtype 1. CONCLUSIONS: TAC/BTX-A therapy exhibited enhanced and sustained clinical efficacy in relieving scar itch, possibly via modulating epidermal innervation and expression of transient receptor potential vanilloid subtype 1 .