Neuroimmune interactions in the development and chronification of migraine headache.

Migraine is highly prevalent and debilitating. The persistent headaches in this condition are thought to arise from the activation and sensitization of the trigeminovascular pathway. Both clinical and animal model studies have suggested that neuroimmune interactions contribute to the pathophysiology of migraine headache. In this review, we first summarize the findings from human studies implicating the dysregulation of the immune system in migraine, including genetic analyses, measurement of circulatory factors, and neuroimaging data. We next discuss recent advances from rodent studies aimed at elucidating the neuroimmune interactions that manifest at various levels of the trigeminovascular pathway and lead to the recruitment of innate and adaptive immune cells as well as immunocompetent glial cells. These cells reciprocally modulate neuronal activity via multiple pro- and anti-inflammatory mediators, thereby regulating peripheral and central sensitization. Throughout the discussions, we highlight the potential clinical and translational implications of the findings.

Status and hotspot analysis of Qingfei Paidu Decoction for the prevention and treatment of COVID-19 based on bibliometric analysis.

Background: Qingfei Paidu Decoction (QFPDD) has played an important role in the prevention and treatment of COVID-19 infection in China. The present study aims to perform an econometric analysis and visualization of the literature on the treatment of COVID-19 with QFPDD in the Chinese databases and English databases. Methods: Six databases including such as Chinese databases CNKI, VIP, CBM, WANFANG as well as English databases PubMed, Web of Science were searched for publications related to the prevention and treatment of COVID-19 with QFPDD. The institutions, authors, keywords of each publication were cisualized using the software of CiteSpace. Results: A total of 187 literature on the prevention and treatment of novel coronavirus infection with QFPDD were included, of which 145 (77.5%) were in Chinese and 42 (22.5%) were in English. Those publications were written by 926 authors from 383 institutions. There were 78 theoretical studies (41.7%), 63 clinical studies (33.7%), and 46 basic studies (24.6%). The cooperative institutions with the core of "Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences" and "Shanghai University of Chinese Medicine Cross Academy of Science" have been formed, and two core teams with "Wang Yanping" and "Zhang Weidong" have been formed. The keyword analysis showed that the research mainly focuses on pathologic pathogenesis, clinical efficacy, adverse reactions, integrated Chinese and western medicine therapy, network pharmacology research. Conclusion: QFPDD has attracted worldwide attention, mechanism research and clinical research may become a future development trend. Therefore, in-depth basic research and clinical studies with large samples and multi-center cooperation should be carried out to provide high-level evidence-based evidence for the prevention and treatment of COVID-19 with QFPDD.

N6-methyladenosine RNA methylation modification regulates the transcription of viral-derived E (XSR) miRNAs to promote ALV-J replication.

The E (XSR) element located in the 3'UTR of the ALV-J genome has the capability to transcribe and generate viral-derived E (XSR) miRNA. However, the biological function and transcriptional regulation mechanism of this process remain unclear. In this study, the impact of E (XSR) miRNA on ALV-J replication and the regulatory effect of N6-methyladenosine (m6A) methylation on its transcription were investigated. The results demonstrated that E (XSR) miRNA could stimulate ALV-J replication and suppress apoptosis in DF-1 cells in vitro. E (XSR) miRNA's promotion of ALV-J replication was not associated with the type I interferon pathway, but achieved by suppressing the expression of the host GPC5 gene. The transcription of E (XSR) miRNA could be promoted by m6A methylation modification, where m6A modification was found at the A6880 and A7016 sites of ALV-J gRNA. This study provides a new perspective on the transcription of ALV-J E (XSR) miRNA and its regulatory function in ALV-J replication.

Low-Dose Interleukin-2 Reverses Traumatic Brain Injury-Induced Cognitive Deficit and Pain in a Murine Model.

OBJECTIVE: Despite the high prevalence, mild traumatic brain injury (mTBI)-induced chronic headache and cognitive deficits are poorly understood and lack effective treatments. Low-dose interleukin-2 (LD-IL-2) treatment soon after mTBI or overexpressing IL-2 in brain astrocytes prior to injury protects mice from developing post-traumatic headache (PTH)-related behaviors and cognitive decline. The present study addresses a clinically relevant knowledge gap: whether LD-IL-2 treatment long after the initial injury is still effective for chronic PTH and cognitive deficits. METHODS: mTBI was induced by a noninvasive closed-head weight drop method. LD-IL-2 was administered 4-6 weeks post-mTBI to assess its effects on chronic PTH-related facial mechanical hypersensitivity as well as mTBI-induced impairment in novel object recognition and object location tests. Endogenous regulatory T (Treg) cells were depleted to investigate the mechanism of action of LD-IL-2. RESULTS: Delayed LD-IL-2 treatment abolished chronic PTH-related behaviors. It also completely reversed mTBI-induced cognitive impairment in both male and female mice. Treg cell depletion not only prolonged PTH-related behaviors but also abolished the effects of LD-IL-2. Interestingly, LD-IL-2 treatment significantly increased the number of Treg cells in dura but not in brain tissues. INTERPRETATION: These results suggest that the beneficial effects of LD-IL-2 treatment are mediated through the expansion of meningeal Treg cells. Collectively, our study identifies Treg as a cellular target and LD-IL-2 as a promising therapy for both chronic PTH and mTBI-induced cognitive impairment for both males and females, with a wide therapeutic time window and the potential of reducing polypharmacy in mTBI treatment. ANN NEUROL 2024;96:508-525.

Impact of foot progression angle on spatiotemporal and plantar loading pattern in intoeing children during gait.

Intoeing in children is a common parental concern, but our understanding of the impact of foot progression angle (FPA) in these children leaves remains limited. This study examines the relationship between FPA and plantar loading pattern, as well as gait symmetry in children with intoeing. The sample included 30 children with intoeing caused by internal tibial torsion, uniformly divided into three groups: unilateral intoeing, bilateral mild intoeing, and bilateral mild-moderate intoeing. The relationship between FPA and plantar loading pattern, and gait symmetry within and among groups were assessed using dynamic pedobarographic and spatiotemporal data. Results indicated a significant correlation between FPA and peak pressure, maximum force, and plantar impulse in the medial and central forefoot, and also the medial and lateral heel zones for both bilateral intoeing groups. Significant differences were observed only in subdivided stance phase, including loading response, single support, and pre-swing phases, between the unilateral intoeing and bilateral mild intoeing groups. These findings suggest that FPA significantly affects the forefoot and heel zones, potentially increasing the load on the support structures and leading to transverse arch deformation. While children with intoeing demonstrate a dynamic self-adjustment capability to maintain gait symmetry, this ability begins to falter as intoeing becomes more pronounced.

[Acupuncture combined with tuina therapy for stiff neck with levator scapula injury type: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of acupuncture combined with tuina therapy for stiff neck with levator scapula injury type. METHODS: A total of 162 patients with stiff neck of levator scapula injury type were randomly divided into an acupuncture combined with tuina group (combined group, 52 patients), a tuina group (55 patients), and an acupuncture group (55 patients). The patients in the acupuncture group received acupuncture on the affected side's Houxi (SI 3), inserting the needle 10 to 20 mm towards Laogong (PC 8) with strong or moderate stimulation, and patients were instructed to move their neck, shoulders, and upper limbs during the process, with the needle retained for 2 to 3 min. The patients in the tuina group received strong stimulation pressing on tender points to release the starting and ending points of the trapezius muscle with modified techniques. The combined group first received tuina therapy, followed immediately by acupuncture treatment at the Houxi (SI 3). Treatments were administered every other day for a total of three sessions. Before treatment and on 1, 3, and 7 days after treatment, the simple McGill pain questionnaire (SF-MPQ) scores [including the pain rating index (PRI), visual analogue scale (VAS), and present pain intensity (PPI) scores] of the head, neck and shoulder, cervical spine mobility scores were observed, and the clinical efficacy and safety of each group were evaluated. RESULTS: On the 1, 3, and 7 days after treatment, the SF-MPQ, PRI, VAS, and PPI scores of the head, neck, and shoulder in all groups were significantly reduced (P<0.01). On the 1 and 3 days after treatment, the above scores in the combined group were lower than those in the tuina group and the acupuncture group (P<0.05, P<0.01). On the 7 days after treatment, the above scores in the combined group were lower than those in the acupuncture group (P<0.01). On the 3 days after treatment, the SF-MPQ, PRI, and VAS scores in the tuina group were lower than those in the acupuncture group (P<0.01). On the 7 days after treatment, the SF-MPQ, PRI, VAS, and PPI scores in the tuina group were lower than those in the acupuncture group (P<0.01, P<0.05). On the 1, 3, and 7 days after treatment, the cervical spine mobility scores in each group were decreased compared to those before treatment (P<0.01). On the 3 days after treatment, the cervical spine mobility score in the combined group was lower than that in the acupuncture group and the tuina group (P<0.01). On the 1, 3, and 7 days after treatment, the cured rate in the combined group was higher than that in the tuina group and the acupuncture group (P<0.01). During the treatment period, no serious adverse reactions occurred in any group. CONCLUSION: Acupuncture combined with tuina therapy could effectively improve stiff neck with levator scapula injury type, alleviate patient pain, restore cervical spine mobility, and clinically outperform both tuina and acupuncture therapy alone.

Nanoparticle Polymeric Micellar Paclitaxel Versus Paclitaxel for Patients with Advanced Gastric Cancer.

BACKGROUND: Nanoparticle polymeric micellar paclitaxel (NPMP) is a novel Cremophor EL (CrEL)-free nanoparticle micellar formulation of paclitaxel. This study evaluated the efficacy and toxicity of NPMP in the treatment of patients with advanced gastric cancer (AGC). METHODS: Patients with histologically confirmed AGC in Jiangsu Cancer Hospital were retrospectively collected and divided into two groups. Patients in group A received NPMP at a total dose of 360 mg/m2 each cycle, and patients in group B were given paclitaxel at a dose of 210 mg/m2 each cycle. In addition, all patients received 5-fluorouracil at a dose of 0.75 g/m2 on days 1-4 and leucovorin at a dose of 200 mg/m2 on days 1-4 for at least 2 cycles. RESULTS: From January 2021 to May 2023, 63 patients (32 in group A and 31 in group B) could be evaluated for treatment response. A marked disparity in the overall response was observed between groups A and B, indicating statistical significance. The overall response rate was 31% in group A (10/32) and 10% in group B (3/31) (P = 0.034). Disease control rate was 91% in group A (29/32) and 81% in group B (25/31) (P = 0.440). No statistically significant difference in adverse reactions was observed between the two groups. However, the incidence of anemia, leucopenia, nausea, vomiting, diarrhea, liver dysfunction, and allergy in group A was notably lower than that in group B. CONCLUSIONS: NPMP combined chemotherapy offers a new, active, and safe treatment for patients with AGC.

A Bursaphelenchus xylophilus effector BxICD1 inducing plant cell death, concurrently contributes to nematode virulence and migration.

The migratory endoparasitic phytonematodes Bursaphelenchus xylophilus is the causal agent of pine wilt disease and causes significant economic damage to pine forests in China. Effectors play a key role in the successful parasitism of plants by phytonematodes. In this study, 210 genes obtained by transcriptomics analyses were found to be upregulated in B. xylophilus infecting Pinus massoniana that were not functionally annotated nor reported previously in B. xylophilus infecting P. thunbergii. Among these differentially expressed genes, a novel effector, BxICD1, that could induce cell death in the extracellular space of Nicotiana benthamiana was identified. BxICD1 was upregulated in the early stages of infection, as shown by RT-qPCR analyses. In situ hybridization analysis showed that BxICD1 was expressed in the esophageal gland of nematodes. The yeast signal sequence trap system indicated that BxICD1 possessed an N-terminal signal peptide with secretion functionality. Using an Agrobacterium-mediated transient expression system, it was demonstrated that the cell death-inducing activity of BxICD1 was dependent on N. benthamiana brassinosteroid-insensitive 1-associated kinase 1 (NbBAK1). Finally, BxICD1 contributed to B. xylophilus virulence and migration in host pine trees, as demonstrated by RNAi silencing assays. These findings indicate that BxICD1 both induces plant cell death and also contributes to nematode virulence and migration in P. massonian.

A Cataract-Causing Mutation in the TRPM3 Cation Channel Disrupts Calcium Dynamics in the Lens.

TRPM3 belongs to the melastatin sub-family of transient receptor potential (TRPM) cation channels and has been shown to function as a steroid-activated, heat-sensitive calcium ion (Ca2+) channel. A missense substitution (p.I65M) in the TRPM3 gene of humans (TRPM3) and mice (Trpm3) has been shown to underlie an inherited form of early-onset, progressive cataract. Here, we model the pathogenetic effects of this cataract-causing mutation using 'knock-in' mutant mice and human cell lines. Trpm3 and its intron-hosted micro-RNA gene (Mir204) were strongly co-expressed in the lens epithelium and other non-pigmented and pigmented ocular epithelia. Homozygous Trpm3-mutant lenses displayed elevated cytosolic Ca2+ levels and an imbalance of sodium (Na+) and potassium (K+) ions coupled with increased water content. Homozygous TRPM3-mutant human lens epithelial (HLE-B3) cell lines and Trpm3-mutant lenses exhibited increased levels of phosphorylated mitogen-activated protein kinase 1/extracellular signal-regulated kinase 2 (MAPK1/ERK2/p42) and MAPK3/ERK1/p44. Mutant TRPM3-M65 channels displayed an increased sensitivity to external Ca2+ concentration and an altered dose response to pregnenolone sulfate (PS) activation. Trpm3-mutant lenses shared the downregulation of genes involved in insulin/peptide secretion and the upregulation of genes involved in Ca2+ dynamics. By contrast, Trpm3-deficient lenses did not replicate the pathophysiological changes observed in Trpm3-mutant lenses. Collectively, our data suggest that a cataract-causing substitution in the TRPM3 cation channel elicits a deleterious gain-of-function rather than a loss-of-function mechanism in the lens.

Inhibition of p38 MAPK/NF-κB p65 signaling pathway activity by rare ginsenosides ameliorates cyclophosphamide-induced premature ovarian failure and KGN cell injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Mey., one of the most used herbs in the world, shows effective treatment in reproductive injury. Recent studies have proven that the processed product, red ginseng, which is more active than ginseng itself. Therefore, it is speculated that its main functional component, rare ginsenosides (heat-transformed saponin, HTS), may be effective in treating premature ovarian failure (POF), but its efficacy has not yet been experimentally confirmed. AIM OF THE STUDY: To evaluate whether HTS could attenuate cyclophosphamide-induced inflammation and oxidative damage in POF model rats and the human granulosa-like KGN cell line and protect granulosa cell proliferation. MATERIAL AND METHODS: HTS were isolated from ginsenosides and high performance liquid chromatography (HPLC) analysis was used to analyze the HTS components. Cyclophosphamide (CP) was used to establish a POF rat model and KGN cell injury model. Reactive oxygen species (ROS) and antioxidant enzyme production was determined using specific assays, while inflammatory cytokine secretion was measured by enzyme-linked immunosorbent assay (ELISA). The proliferative function of granulosa cells was assessed using high-content screening and immunohistochemistry to determine the Ki67 protein level. Protein expression in ovarian tissues and KGN cells was analyzed by Western blotting, quantitative real-time PCR (qRT-PCR) was used to determine the transcriptional changes in ovarian tissues and KGN cells. RESULTS: In CP-treated POF model rats, HTS significantly decreased malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels, increased glutathione oxidase (GSH) levels, and upregulated Ki67 expression in ovarian granulosa cells. In addition, HTS significantly increased cell survival and Ki67 expression levels in CP-treated cells, and superoxide dismutase (SOD) levels were significantly increased. HTS significantly downregulated IL-6, TNF-α, and interleukin-1ß (IL-1ß) mRNA expression and significantly inhibited nuclear factor kappa-B p65 (NF-κB p65) and p38 mitogen activated protein kinase (p38 MAPK) phosphorylation in POF model rats and KGN cells. Moreover, NF-κB p65 and p38 MAPK levels were significantly increased in ovarian granulosa cells. p65 and p38 protein and gene expression was significantly downregulated. CONCLUSION: HTS ameliorated CP-induced POF and human granulosa cell injury, possibly by inhibiting inflammation and oxidative damage mediated by the p38 MAPK/NF-κB p65 signaling pathway.

Saponins from Chenopodium quinoa Willd. husks alleviated high-fat-diet-induced hyperlipidemia via modulating the gut microbiota and multiple metabolic pathways.

BACKGROUND: Hyperlipidemia is characterized by abnormally elevated blood lipids. Quinoa saponins (QS) have multiple pharmacological activities, including antitumor, bactericidal and immune-enhancing effects. However, the lipid-lowering effect and mechanisms of QS in vivo have been scarcely reported. METHODS: The effect of QS against hyperlipidemia induced by high-fat diet in rats was explored based on gut microbiota and serum non-targeted metabolomics. RESULTS: The study demonstrated that the supplementation of QS could reduce serum lipids, body weight, liver injury and inflammation. 16S rRNA sequencing demonstrated that QS mildly increased alpha-diversity, altered the overall structure of intestinal flora, decreased the relative richness of Firmicutes, the ratio of Firmicutes/Bacteroidetes (P < 0.05) and increased the relative richness of Actinobacteria, Bacteroidetes, Bifidobacterium, Roseburia and Coprococcus (P < 0.05). Simultaneously, metabolomics analysis showed that QS altered serum functional metabolites with respect to bile acid biosynthesis, arachidonic acid metabolism and taurine and hypotaurine metabolism, which were closely related to bile acid metabolism and fatty acid ß-oxidation. Furthermore, QS increased protein levels of farnesoid X receptor, peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase 1, which were related to the screened metabolic pathways. Spearman correlation analysis showed that there was a correlation between gut microbiota and differential metabolites. CONCLUSION: QS could prevent lipid metabolism disorders in hyperlipidemic rats, which may be closely associated with the regulation of the gut microbiota and multiple metabolic pathways. This study may provide new evidence for QS as natural active substances for the prevention of hyperlipidemia. © 2023 Society of Chemical Industry.

Optimization of green deep eutectic solvent (DES) extraction of Chenopodium quinoa Willd. husks saponins by response surface methodology and their antioxidant activities.

Quinoa saponins have outstanding activity, and there are an increasing number of extraction methods, but there are few research programs on green preparation technology. The extraction conditions of quinoa saponins with deep eutectic solvents (DESs) were optimized by single-factor experiments combined with response surface methodology. The antioxidant capacity of saponins extracted by DESs and traditional methods was evaluated by the DPPH clearance rate, iron ion chelation rate and potassium ferricyanide reducing power. The results show that the optimal DES is choline chloride: 1,2-propylene glycol (1 : 1), and its water content is 40%. The optimal extraction conditions were as follows: the solid-to-solvent ratio was 0.05 g mL-1, the extraction time was 89 min, and the extraction temperature was 75 °C. Under these conditions, the extraction of quinoa saponins by DES was more effective than the traditional extraction methods. The saponins extracted by DES and traditional methods were analyzed by UPLC-MS, and five main saponins were identified. Quantitative analysis by HPLC-UV showed that Q1 (m/z = 971) and Q2 (m/z = 809) had higher contents of saponins. In vitro antioxidant experiments showed that all DES saponin extracts showed good antioxidant capacity. This study provides new insight into the development and utilization of quinoa saponins.

Safety evaluation of rare ginsenosides of stems and leaves from American ginseng: 90-day exposure toxicity study combined with intestinal flora analysis and metabonomics in rats.

Rare ginsenosides have already been widely applied in many fields, including health food and bio-medicine. The human being can expose to rare ginsenosides directly or indirectly increasingly. However, there are few studies on the safety assessment of rare ginsenoside mixtures. In the present study, the sub-chronic toxicity of rare ginsenosides for 90 days on SD rats was performed by combining the intestinal flora analysis and urine metabonomics aiming to illustrate the safety of long-term consumption of rare ginsenosides and the potential damage for liver and intestinal. 48 adult rats were divided into four groups: control (0 mg/kg), low-dose (60 mg/kg), medium-dose (200 mg/kg), and high-dose (600 mg/kg). Rats in the high-dose group showed inflammatory changes in their livers and intestines. The strong bactericidal effect of rare ginsenosides caused intestinal flora disorder and changed the structure of intestinal flora in rats, thus inducing intestinal damage in rats. In the high-dose group, levels of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (AKP) increased significantly. As a result of the high-dose treatment, certain metabolic pathways were altered, such as vitamin B6 metabolism, methionine metabolism, glutathione metabolism, and others. These results indicated that high doses of rare ginsenosides induced liver injury by affecting the above metabolic pathways. Rare ginsenosides with no observed adverse effect level (NOAEL) were below 200 mg/kg/day in vivo. Thus, this present study provides insight into the rational use of rare ginsenosides.

Differential interference of copper with endophytic bacterial inoculation: Atrazine decontamination in Acorus tatarinowii and culture solution.

To clarify the interference effects of inorganic ions, Acorus tatarinowii and endophytic bacterium Herbaspirillum huttiense (Hh) were combined to decontaminate atrazine pollution under different copper levels. This study verified inoculation effects and revealed the complicated processes of atrazine transformation in solutions. 35.9% leaf biomass was promoted by Hh inoculation, and the value was lowered to 7.87% by high doses of copper. The changing trend of leaf N, K, and S contents, and tiller numbers were consistent with that of leaf biomass. Hh injection improved atrazine accumulation by 43.5% in roots, and under copper interference, this value lowered to 10.6%. Hh promoted atrazine deethylation in plants, which was copper-dose dependent in different plant organs. In solutions, atrazine was conjugated with small-molecule secretions at m/z 118, detoxicated into 2-hxydroatrazine and 2-hydroxy-4-acetamido-atrazine, then the triazine ring opened. Copper interference had a more significant impact on residual atrazine conversion products than Hh inoculation treatments. Hh treatment promoted the ring-opening degradation of atrazine in water. The addition of high doses of copper ions promoted the oxidative process of atrazine while inhibiting its ring-opening transformation process in water.

Health risk cause of water around landfill in hilly area and prevention and control countermeasures.

Evaluating the health risks of the groundwater and surface water in landfill areas is of great significance to the health and safety of local residents. The current practice of health risk assessment is based only on the analysis results of groundwater and surface water samples, which reflect the current situation of water security in landfill areas. However, due to the neglect of risk causes analysis, thus a health risk assessment is insufficient to provide rigorous scientific countermeasures for risk prevention and control. The health risks caused by groundwater and surface water is mainly controlled by the water quality, which is comprehensively controlled by the conditions of its formation and evolution. When a landfill site is located in a hilly area, the environmental characteristics, causes, main controlling factors, and evolution processes of the surface water and groundwater in different parts of the catchment are significantly different. This study used a municipal solid waste landfill area in a hilly area as an example and defined the causes and main controlling factors of regional health risks caused by water based on an analysis of the characteristics of natural and anthropogenic factors affecting the groundwater and surface water. Then, prevention and control countermeasures were proposed for health risks caused by water in different parts of the landfill area. This study provides a method for the causes analysis and prevention and control countermeasures of health risks caused by water in municipal solid waste landfills in hilly areas.

Bringing Artificial Intelligence to the operating room: edge computing for real-time surgical phase recognition.

BACKGROUND: Automation of surgical phase recognition is a key effort toward the development of Computer Vision (CV) algorithms, for workflow optimization and video-based assessment. CV is a form of Artificial Intelligence (AI) that allows interpretation of images through a deep learning (DL)-based algorithm. The improvements in Graphic Processing Unit (GPU) computing devices allow researchers to apply these algorithms for recognition of content in videos in real-time. Edge computing, where data is collected, analyzed, and acted upon in close proximity to the collection source, is essential meet the demands of workflow optimization by providing real-time algorithm application. We implemented a real-time phase recognition workflow and demonstrated its performance on 10 Robotic Inguinal Hernia Repairs (RIHR) to obtain phase predictions during the procedure. METHODS: Our phase recognition algorithm was developed with 211 videos of RIHR originally annotated into 14 surgical phases. Using these videos, a DL model with a ResNet-50 backbone was trained and validated to automatically recognize surgical phases. The model was deployed to a GPU, the Nvidia® Jetson Xavier™ NX edge computing device. RESULTS: This model was tested on 10 inguinal hernia repairs from four surgeons in real-time. The model was improved using post-recording processing methods such as phase merging into seven final phases (peritoneal scoring, mesh placement, preperitoneal dissection, reduction of hernia, out of body, peritoneal closure, and transitionary idle) and averaging of frames. Predictions were made once per second with a processing latency of approximately 250 ms. The accuracy of the real-time predictions ranged from 59.8 to 78.2% with an average accuracy of 68.7%. CONCLUSION: A real-time phase prediction of RIHR using a CV deep learning model was successfully implemented. This real-time CV phase segmentation system can be useful for monitoring surgical progress and be integrated into software to provide hospital workflow optimization.

Surgical Phase Recognition in Inguinal Hernia Repair-AI-Based Confirmatory Baseline and Exploration of Competitive Models.

Video-recorded robotic-assisted surgeries allow the use of automated computer vision and artificial intelligence/deep learning methods for quality assessment and workflow analysis in surgical phase recognition. We considered a dataset of 209 videos of robotic-assisted laparoscopic inguinal hernia repair (RALIHR) collected from 8 surgeons, defined rigorous ground-truth annotation rules, then pre-processed and annotated the videos. We deployed seven deep learning models to establish the baseline accuracy for surgical phase recognition and explored four advanced architectures. For rapid execution of the studies, we initially engaged three dozen MS-level engineering students in a competitive classroom setting, followed by focused research. We unified the data processing pipeline in a confirmatory study, and explored a number of scenarios which differ in how the DL networks were trained and evaluated. For the scenario with 21 validation videos of all surgeons, the Video Swin Transformer model achieved ~0.85 validation accuracy, and the Perceiver IO model achieved ~0.84. Our studies affirm the necessity of close collaborative research between medical experts and engineers for developing automated surgical phase recognition models deployable in clinical settings.

Functional fungal pellets self-immobilized by mycelium fragments of Irpex lacteus WRF-IL for efficient degradation of sulfamethazine as the sole carbon source.

In order to achieve an efficient microbial material with dual functions of self-immobilization and sulfamethazine (SMZ) degradation, this study explored the pelletization technique utilizing mycelium fragments of Irpex lacteus WRF-IL and systematically examined the pellets formation conditions and degradation capability. The Box-Behnken design results demonstrated that pure mycelium fragments, broken by frosted glass beads, could be rapidly self-immobilized to form white rot mycelial pellets (WRMPs) within 24 h, serving as the pelleting core. These WRMPs could completely remove SMZ as the sole carbon source within 20 h. The addition of sucrose expedited this process, achieving complete removal within only 14 h. Kinetic analysis showed that WRMPs could potentially remove SMZ at higher concentrations (>25 mg/L). Biodegradation was the primary pathway of SMZ removal. Seven intermediates were identified by QTOF LC/MS, and three transformation pathways initiated by SO2 overflow, molecular rearrangement, and aniline moiety oxidation were deduced.

Peripheral CCL2-CCR2 signalling contributes to chronic headache-related sensitization.

Migraine, especially chronic migraine, is highly debilitating and still lacks effective treatment. The persistent headache arises from activation and sensitization of primary afferent neurons in the trigeminovascular pathway, but the underlying mechanisms remain incompletely understood. Animal studies indicate that signalling through chemokine C-C motif ligand 2 (CCL2) and C-C motif chemokine receptor 2 (CCR2) mediates the development of chronic pain after tissue or nerve injury. Some migraine patients had elevated CCL2 levels in CSF or cranial periosteum. However, whether the CCL2-CCR2 signalling pathway contributes to chronic migraine is not clear. Here, we modelled chronic headache with repeated administration of nitroglycerin (NTG, a reliable migraine trigger in migraineurs) and found that both Ccl2 and Ccr2 mRNA were upregulated in dura and trigeminal ganglion (TG) tissues that are implicated in migraine pathophysiology. In Ccl2 and Ccr2 global knockout mice, repeated NTG administration did not evoke acute or persistent facial skin hypersensitivity as in wild-type mice. Intraperitoneal injection of CCL2 neutralizing antibodies inhibited chronic headache-related behaviours induced by repeated NTG administration and repetitive restraint stress, suggesting that the peripheral CCL2-CCR2 signalling mediates headache chronification. We found that CCL2 was mainly expressed in TG neurons and cells associated with dura blood vessels, whereas CCR2 was expressed in subsets of macrophages and T cells in TG and dura but not in TG neurons under both control and disease states. Deletion of Ccr2 gene in primary afferent neurons did not alter NTG-induced sensitization, but eliminating CCR2 expression in either T cells or myeloid cells abolished NTG-induced behaviours, indicating that both CCL2-CCR2 signalling in T cells and macrophages are required to establish chronic headache-related sensitization. At cellular level, repeated NTG administration increased the number of TG neurons that responded to calcitonin-gene-related peptide (CGRP) and pituitary adenylate cyclase activating polypeptide (PACAP) as well as the production of CGRP in wild-type but not Ccr2 global knockout mice. Lastly, co-administration of CCL2 and CGRP neutralizing antibodies was more effective in reversing NTG-induced behaviours than individual antibodies. Taken together, these results suggest that migraine triggers activate CCL2-CCR2 signalling in macrophages and T cells. This consequently enhances both CGRP and PACAP signalling in TG neurons, ultimately leading to persistent neuronal sensitization underlying chronic headache. Our work not only identifies the peripheral CCL2 and CCR2 as potential targets for chronic migraine therapy, but also provides proof-of-concept that inhibition of both peripheral CGRP and CCL2-CCR2 signalling is more effective than targeting either pathway alone.

Monocytes reprogrammed by tumor microparticle vaccine inhibit tumorigenesis and tumor development.

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy. Supplementary Information: The online version contains supplementary material available at 10.1186/s12645-023-00190-x.