Exploring the possible relationship between skin microbiome and brain cognitive functions: a pilot EEG study.

Human microbiota mainly resides on the skin and in the gut. Human gut microbiota can produce a variety of short chain fatty acids (SCFAs) that affect many physiological functions and most importantly modulate brain functions through the bidirectional gut-brain axis. Similarly, skin microorganisms also have identical metabolites of SCFAs reported to be involved in maintaining skin homeostasis. However, it remains unclear whether these SCFAs produced by skin bacteria can affect brain cognitive functions. In this study, we hypothesize that the brain's functional activities are associated with the skin bacterial population and examine the influence of local skin-bacterial growth on event-related potentials (ERPs) during an oddball task using EEG. Additionally, five machine learning (ML) methods were employed to discern the relationship between skin microbiota and cognitive functions. Twenty healthy subjects underwent three rounds of tests under different conditions-alcohol, glycerol, and water. Statistical tests confirmed a significant increase in bacterial population under water and glycerol conditions when compared to the alcohol condition. The metabolites of bacteria can turn phenol red from red-orange to yellow, confirming an increase in acidity. P3 amplitudes were significantly enhanced in response to only oddball stimulus at four channels (Fz, FCz, and Cz) and were observed after the removal of bacteria when compared with that under the water and glycerol manipulations. By using machine learning methods, we demonstrated that EEG features could be separated with a good accuracy (> 88%) after experimental manipulations. Our results suggest a relationship between skin microbiota and brain functions. We hope our findings motivate further study into the underlying mechanism. Ultimately, an understanding of the relationship between skin microbiota and brain functions can contribute to the treatment and intervention of diseases that link with this pathway.

Neutrophil Targeting Platform Reduces Neutrophil Extracellular Traps for Improved Traumatic Brain Injury and Stroke Theranostics.

Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia-reperfusion injury (CIRI), in addition to the blood-brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)-responsive neutrophil-targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

B cell memory: from generation to reactivation: a multipronged defense wall against pathogens.

Development of B cell memory is a conundrum that scientists are still exploring. Studies have been conducted in vitro and using advanced animal models to elucidate the mechanism underlying the generation of memory B cells (MBCs), the precise roles of MBCs against pathogens, and their protective functions against repeated infections throughout life. Lifelong immunity against invading diseases is mainly the result of overcoming a single infection. This protection is largely mediated by the two main components of B cell memory-MBCs and long-lived plasma cells (PCs). The chemical and cellular mechanisms that encourage fat selection for MBCs or long-lived PCs are an area of active research. Despite the fact that nearly all available vaccinations rely on the capacity to elicit B-cell memory, we have yet to develop successful vaccines that can induce broad-scale protective MBCs against some of the deadliest diseases, including malaria and AIDS. A deeper understanding of the specific cellular and molecular pathways that govern the generation, function, and reactivation of MBCs is critical for overcoming the challenges associated with vaccine development. Here, we reviewed literature on the development of MBCs and their reactivation, interaction with other cell types, strategies against invading pathogens, and function throughout life and discussed the recent advances regarding the key signals and transcription factors which regulate B cell memory and their relevance to the quest for vaccine development.

Graded-Band-Gap Zinc-Tin Oxide Thin-Film Transistors with a Vertically Stacked Structure for Wavelength-Selective Photodetection.

Filter-free wavelength-selective photodetectors have garnered significant attention due to the growing demand for smart sensors, artificial intelligence, the Internet of Everything, and so forth. However, the challenges associated with large-scale preparation and compatibility with complementary metal-oxide-semiconductor (CMOS) technology limit their wide-ranging applications. In this work, we address the challenges by constructing vertically stacked graded-band-gap zinc-tin oxide (ZTO) thin-film transistors (TFTs) specifically designed for wavelength-selective photodetection. The ZTO thin films with various band gaps are fabricated via atomic layer deposition (ALD) by varying the ALD cycle ratios of zinc oxide (ZnO) and SnO2. The ZTO film with a small Sn ratio exhibits a decreased band gap, and the resultant TFT shows a degraded performance, which can be attributed to the Sn4+ dopant introducing a series of deep-state energy levels in the ZnO band gap. As the ratio of Sn increases further, the band gap of the ZTO also increases, and the mobility of the ZTO TFT increases up to 30 cm2/V s, with a positive shift of the threshold voltage. The photodetectors employing ZTO thin films with distinct band gaps show different spectral responsivities. Then, vertically stacked ZTO (S-ZTO) thin films, with gradient band gaps increasing from the bottom to the top, have been successfully deposited using consecutive ALD technology. The S-ZTO TFT shows decent performance with a mobility of 18.4 cm2/V s, a threshold voltage of 0.5 V, an on-off current ratio higher than 107, and excellent stability under ambient conditions. The resultant S-ZTO TFT also exhibits obviously distinct photoresponses to light at different wavelength ranges. Furthermore, a device array of S-ZTO TFTs demonstrates color imaging by precisely reconstructing patterned illuminations with different wavelengths. Therefore, this work provides CMOS-compatible and structure-compact wavelength-selective photodetectors for advanced and integrable optoelectronic applications.

Magnetic resonance imaging-based radiomics and deep learning models for predicting lymph node metastasis of squamous cell carcinoma of the tongue.

OBJECTIVE: This study aimed to establish a combined method of radiomics and deep learning (DL) in magnetic resonance imaging (MRI) to predict lymph node metastasis (LNM) preoperatively in patients with squamous cell carcinoma of the tongue. STUDY DESIGN: In total, MR images of 196 patients with lingual squamous cell carcinoma were divided into training (n = 156) and test (n = 40) cohorts. Radiomics and DL features were extracted from MR images and selected to construct machine learning models. A DL radiomics nomogram was established via multivariate logistic regression by incorporating the radiomics signature, the DL signature, and MRI-reported LN status. RESULTS: Nine radiomics and 3 DL features were selected. In the radiomics test cohort, the multilayer perceptron model performed best with an area under the receiver operating characteristic curve (AUC) of 0.747, but in the DL cohort, the best model (logistic regression) performed less well (AUC = 0.655). The DL radiomics nomogram showed good calibration and performance with an AUC of 0.934 (outstanding discrimination ability) in the training cohort and 0.757 (acceptable discrimination ability) in the test cohort. The decision curve analysis demonstrated that the nomogram could offer more net benefit than a single radiomics or DL signature. CONCLUSION: The DL radiomics nomogram exhibited promising performance in predicting LNM, which facilitates personalized treatment of tongue cancer.

CD206+ M2-like macrophages protect against intervertebral disc degeneration partially by targeting R-spondin-2.

OBJECTIVE: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). METHODS: Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD. IDD-induced damage and cell apoptosis were measured using histological scoring, X-ray imaging, immunohistochemical staining, and TdT-mediated dUTP nick end labeling (TUNEL) assay. Finally, mice and NPCs were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in IDD. RESULTS: Accumulation of CD206 in human and mouse IDD tissues was detected. Rheb deletion in the myeloid lineage (RheBcKO) increased the number of CD206+ M2-like macrophages (mean difference 18.6% [15.7-21.6%], P < 0.001), decreased cell apoptosis (mean difference -15.6% [-8.9 to 22.2%], P = 0.001) and attenuated the IDD process in the mouse IDD model. NPCs treated with Rspo2 displayed increased extracellular matrix catabolism and apoptosis; co-culture with a conditioned medium derived from RheBcKO mice inhibited these changes. Anti-Rspo2 treatment in the mouse caudal IVD puncture model exerted protective effects against IDD. CONCLUSIONS: Promoting CD206+ M2-like macrophages could reduce Rspo2 secretion, thereby alleviating experimental IDD. Rheb deletion may help M2-polarized macrophages accumulate and attenuate experimental IDD partially by inhibiting Rspo2 production. Hence, M2-polarized macrophages and Rspo2 may serve as therapeutic targets for IDD.

Anchored sutures for fixation of the anterolateral thigh flap and prevention of orocutaneous fistula in oral and oropharyngeal cancer reconstruction.

OBJECTIVE: This study aims to assess the efficacy of anchored sutures (AS) in securing the anterolateral thigh (ALT) flap during oral and oropharyngeal reconstructions, and its impact on the occurrence of orocutaneous fistula (OCF). MATERIALS AND METHODS: A retrospective study was performed on patients who underwent ALT flap reconstruction in our department in the year 2022. The patients were divided into two groups based on whether the AS technique was used. The incidence of OCF was compared between the two groups, and AS-related complications were reported. Fisher's exact test was employed to assess the differences in baseline characteristics and the incidence of OCF between the two groups. RESULTS: The study included 214 patients, with 156 in the conventional suture (CS) group and 58 in the AS group. The incidence of OCF in the AS group was significantly lower compared to that in the CS group (P = 0.039). However, there was a weak correlation between OCF and the AS technique (φ = -0.149). Among the 58 cases in the AS group, three (5.17%) experienced AS-related granuloma (ASRG) as complications. CONCLUSION: The use of ALT flap reconstruction with the AS technique reduces the incidence of OCF; however, ASRG may be a potential complication. CLINICAL RELEVANCE: This study demonstrates the effectiveness of AS technique in securing ALT flaps, leading to a decreased risk of OCF in oral and oropharyngeal defect reconstruction.

Studies of a novel bone-targeted nano drug delivery system with a HAP core-PSI coating structure for tanshinol injection.

Tanshinol (Tan) has good therapeutic effects on osteoporosis, fracture, and bone trauma repair. However, it is easily oxidised, has low bioavailability and a short half-life. To solve these problems, the study aimed to develop a novel bone-targeted nano-sustained-release drug delivery system PSI-HAPs for the systemic administration of Tan. This proposed system has hydroxyapatite (HAP) as the core to load drug and polysuccinimide (PSI), PEG-PSI (Polyethylene glycol, PEG), and ALN-PEG-PSI (Alendronate sodium, ALN) as the coating materials to form nanoparticles. The article examines the various PSI-HAPs' entrapping efficiency (EE, %), drug loading capacity (DLC, %), and distribution to determine the best PSI-HAP formulation in vivo. The in vivo experiment showed that the ALN-PEG-PSI-HAP (ALN-PEG/PSI molar ratio = 1:20) was the best preparation due to its higher distribution on bone (120 h) and lower distribution in the other tissues. The determined preparation was a uniformly spherical or sphere-like nanoparticle with a negative zeta potential. Additionally, it exhibited pH-sensitive drug release in PBS based on an in vitro drug release test. The proposed PSI-HAP preparations were prepared in the water solution using a facile preparation process without ultrasound, heating, and other conditions, which can significantly affect the stability of drugs.

Influence of macrophage polarization in herniated nucleus pulposus tissue on clinical efficacy after lumbar discectomy.

Background: Low back pain or sciatic pain because of lumbar intervertebral disc herniation (LDH) is caused by mechanical compression and/or an inflammatory component on the nerve root. However, it is difficult to define to what extent each component contributes to the pain. This study attempted to explore the effects of macrophage polarization on clinical symptoms in patients experiencing LDH after surgery, and investigated the association between macrophage cell percentages and clinical efficacy. Methods: This study retrospectively harvested nucleus pulposus (NP) tissue samples from 117 patients. Clinical symptoms and efficacy using the visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated at different time points preoperatively and postoperatively. CD68, CCR7, CD163, and CD206 were selected as macrophage phenotypic markers. Results: Seventy-six samples showed positive expression of macrophage markers in NP samples of patients with LDH, whereas 41 patients displayed negative results. No significant differences were detected between the two groups, involvement of several demographic data, and preoperative clinical findings. With respect to the macrophage-positive group, no significant correlation was detected between the positive rate of the four markers and the VAS score or ODI after surgery. However, patients with NP samples positive for CD68 and CCR7 expression showed significantly lower VAS scores 1 week after surgery compared with those in the negative group. Moreover, the improvement in VAS score showed a strong positive correlation with CD68- and CCR7-positive cell percentages. Conclusions: Our results indicated that pro-inflammatory M1 macrophages may be associated with the reduction of chronic pain after surgery. Therefore, these findings contribute to better personalized pharmacological interventions for patients with LDH, considering the heterogeneity of pain.

Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy.

Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy. Methods: We retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy. Results: Treatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075). Conclusions: In the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC.

Ligustrazine Nanoparticle Hitchhiking on Neutrophils for Enhanced Therapy of Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood-brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl-F-(D)L-F-(D)L-F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)-responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation-related diseases.

Local Consolidative Therapy May Have Prominent Clinical Efficacy in Patients with EGFR-Mutant Advanced Lung Adenocarcinoma Treated with First-Line Afatinib.

Afatinib is an irreversible tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR), which is utilized for the treatment of patients with advanced lung cancer that harbors EGFR mutations. No studies have evaluated the clinical efficacy of LCT in patients treated with first-line afatinib. In this study, we retrospectively enrolled patients with advanced lung adenocarcinomas harboring susceptible EGFR mutations who were diagnosed and treated with first-line afatinib in three hospitals. A total of 254 patients were enrolled, including 30 (12%) patients who received LCT (15 patients received definitive radiotherapy for the primary lung mass and 15 patients received curative surgery). Patients who received LCT had a significantly longer PFS than those who did not (median PFS: 32.8 vs. 14.5 months, p = 0.0008). Patients who received LCT had significantly longer OS than those who did not (median OS: 67.1 vs. 34.5 months, p = 0.0011). Multivariable analysis showed LCT was an independent prognostic factor for improved PFS (adjusted hazard ratio [aHR] [95% confidence interval (CI)]: 0.44 [0.26-0.73], p = 0.0016) and OS (aHR [95% CI]: 0.26 [0.12-0.54], p = 0.0004). The analyses using propensity score-weighting showed consistent results. We conclude that LCT may improve clinical outcomes, in terms of PFS and OS, in patients with advanced EGFR-mutant lung adenocarcinomas who are treated with first-line afatinib.

Bacillus amyloliquefaciens Increases the GABA in Rice Seed for Upregulation of Type I Collagen in the Skin.

Biosynthesis of gamma-aminobutyric acid (GABA) can be achieved by naturally occurring microorganisms with the advantages of cost-effectiveness and safety. In this study, Bacillus amyloliquefaciens EH-9 strain (B. amyloliquefaciens EH-9), a soil bacterium, was used to promote the accumulation of GABA in germinated rice seed. Further, the topical application of supernatant from rice seed co-cultivated with soil B. amyloliquefaciens EH-9 can significantly increase the production of type I collagen (COL1) in the dorsal skin of mice. The knocking down of the GABA-A receptor (GABAA) significantly reduced the production of COL1 in the NIH/3T3 cells and in the dorsal skin of mice. This result suggests that topical application of GABA can promote the biosynthesis of COL1 via its interaction with the GABAA receptor in the dorsal skin of mice. In summary, our findings illustrate for the first time that soil B. amyloliquefaciens EH-9 elicits GABA production in germinated rice seed to upregulate the formation of COL1 in the dorsal skin of mice. This study is translational because the result shows a potential remedy for skin aging by stimulating COL1 synthesis using biosynthetic GABA associated with B. amyloliquefaciens EH-9.

Lactobacillus plantarum Generate Electricity through Flavin Mononucleotide-Mediated Extracellular Electron Transfer to Upregulate Epithelial Type I Collagen Expression and Thereby Promote Microbial Adhesion to Intestine.

The mechanism behind how flavin mononucleotide (FMN)-producing bacteria attach to a host intestine remains unclear. In order to address this issue, this study isolated the Gram-positive bacteria Lactobacillus plantarum from Mongolian fermented Airag, named L. plantarum MA. These bacteria were further employed as the model microbes, and their electrogenic properties were first identified by their significant expression of type II NADH-quinone oxidoreductase. This study also demonstrated that the electrical activity of L. plantarum MA can be conducted through flavin mononucleotide (FMN)-based extracellular electron transfer, which is highly dependent on the presence of a carbon source in the medium. Our data show that approximately 15 µM of FMN, one of the key electron donors for the generation of electricity, can be produced from L. plantarum MA, as they were cultured in the presence of lactulose for 24 h. We further demonstrated that the electrical activity of L. plantarum MA can promote microbial adhesion and can thus enhance the colonization effectiveness of Caco-2 cells and mouse cecum. Such enhanced adhesiveness was attributed to the increased expression of type I collagens in the intestinal epithelium after treatment with L. plantarum MA. This study reveals the mechanism behind the electrogenic activity of L. plantarum MA and shows how the bacteria utilize electricity to modulate the protein expression of gut tissue for an enhanced adhesion process.

Flexible Microspectrometers Based on Printed Perovskite Pixels with Graded Bandgaps.

Miniaturized spectrometers have attracted much attention due to their capability to detect spectral information within a small size. However, such technology still faces challenges including large-scale preparation and performance repeatability. In this work, we overcome these challenges by demonstrating a microspectrometer constructed with a series of pixelized graded-bandgap perovskite photodetectors fabricated with inkjet printing. High-quality perovskite films with minimal pinholes and large grains are deposited by optimizing printing conditions including substrate temperature and surface modification. The resulting perovskite photodetectors show decent photosensing performance, and the different photodetectors based on perovskite films with different bandgaps exhibit various spectral responsivities with different cutoff wavelength edges. Microspectrometers are then constructed with the array of the pixelized graded-bandgap perovskite photodetectors, and incident spectra are algorithmically reconstructed by combining their output currents. The reconstruction performance of the miniaturized spectrometer is evaluated by comparing the results to the spectral curve measured with a commercial bulky spectrometer, indicating a reliable spectral reconstruction with a resolution of around 10 nm. More significantly, the miniaturized spectrometers are successfully fabricated on polymer substrates, and they demonstrate excellent mechanical flexibility. Therefore, this work provides a flexible miniaturized spectrometer with large-scale fabricability, which is promising for emerging applications including wearable devices, hyperspectral imaging, and internet of things.

Investigation of macrophage polarization in herniated nucleus pulposus of patients with lumbar intervertebral disc herniation.

Macrophage infiltration and polarization during lumbar intervertebral disc herniation (LDH) have attracted increased attention but their role remains unclear. To explore macrophage polarization in herniated nucleus pulposus (NP) tissue of patients with LDH and investigate the association between cell frequency and different clinical characteristics or symptoms, we conducted a retrospective study by analyzing NP tissue samples from 79 patients. Clinical features and symptoms, using the visual analog scale (VAS) and Oswestry disability index (ODI), were collected. The macrophage markers CD68, CCR7, CD163, and CD206; pro-inflammatory cytokine TNF-α; and anti-inflammatory factor IL-4 were analyzed by immunohistochemistry. The frequency of polarized macrophages and positivity rate of pro- and anti-inflammatory cytokines showed significant differences in some of clinical characteristics. Specifically, higher CCR7+ and TNF-α + proportions were identified in the high-intensity zone (HIZ) and the type of extrusion and sequestration NP tissue than in non-HIZ and protrude NP tissue. Higher CD206+ and IL-4+ proportion were detected in Modic changes. However, no differences in gender, age, smoking status, Pfirrmann grade, analgesic use, leg pain duration, and segments were found between groups. CD68+ , CCR7+ , and CD206+ cell proportions, and TNF-α and IL-4 showed positive associations with VAS scores preoperation. Associations between ODI and the macrophages markers were weak/insignificant. Our results indicated that macrophage polarization or macrophage-like cells contribute to LDH pathological features. Macrophage populations displaying significant associations with VAS score reflected continuous M1/M2 transition contributing to pain during LDH. These findings may contribute to enhanced/personalized pharmacological interventions for patients with LDH considering pain heterogeneity.

Intracranial hemorrhage after spinal surgery: a literature review.

Background and Objective: Intracranial hemorrhage following spinal surgery is an infrequent but severe complication. Due to its rarity, the etiology, clinical characteristics, and treatment have not yet been fully elucidated. This literature review analyzed the incidence, clinical manifestations, hemorrhage location, current therapeutic strategies, location of operation, and interval time between surgery and bleeding. The objectives of the article were to provide insights for clinicians to promptly identify and prevent potential cases of intracranial hemorrhage. Methods: The authors queried PubMed and Web of Science databases using predefined keywords and included published literature reporting on intracranial hemorrhage after spinal surgery. Relevant case reports, case series, and reviews describing the mechanism of intracranial hemorrhage after spinal surgery and meeting diagnostic criteria for intracranial hemorrhage related to spinal surgery were included. Clinico-demographc data, presentations symptoms, location, index surgery type, and neurological outcomes after brain hemorrhage. Oxford Centre Level of Evidence guidelines was used to evaluate the quality of included studies. Descriptive statistics were used to synthesize the results. Key Content and Findings: A total of 80 publications of level of evidence IV involving 108 patients with median age at diagnosis was 58.5 years (inter-quartile range: 6-85) were analyzed. The incidence of intracranial hemorrhage was 0.08-0.37% among patients who underwent spinal surgery, and this complication occurred predominantly within 48 hours postoperatively. The initial presentation included headache, reduced level of consciousness, dysarthria, nausea, vomiting, hearing loss, blurred vision, neck rigidity, and delayed recovery from anesthesia. More than half (58.3%) of patients improved, while 23.1% still experienced neurological dysfunctions, and 7.4% died. Conclusions: The present study is limited by the levels of evidence of the included studies. There is heterogeneity among cases with respect to patient demographics and medical history. Angiography is critical in assessing the presence and extent of underlying vascular diseases. Intracranial hemorrages may be caused by intraoperative or postoperative cerebrospinal fluid leakage that will lead to intracranial pressure change and induced by intracranial venous or arterial bleeding. The treatment strategies include conservative medical management and surgical treatment. Individualized treatment should be emphasized.

Extracellular electrons transferred from honey probiotic Bacillus circulans inhibits inflammatory acne vulgaris.

Bacillus circulans (B. circulans) is widely used as an electrogenic bacterium in microbial fuel cell (MFC) technology. This study evaluated whether B. circulans can ferment glucose to generate electricity and mitigate the effects of human skin pathogens. The electricity production of B. circulans was examined by measuring the voltage difference and verified using a ferrozine assay in vitro. To investigate the fermentation effects of B. circulans on inhibition of human skin pathogens, Cutibacterium acnes (C. acnes) was injected intradermally into mice ears to induce an inflammatory response. The results revealed that the glucose-B. circulans co-culture enhanced electricity production and significantly supressed C. acnes growth. The addition of roseoflavin to inhibit flavin production considerably reduced the electrical energy generated by B. circulans through metabolism and, in vivo test, recovered C. acnes count and macrophage inflammatory protein 2 (MIP-2) levels. This suggests that B. circulans can generate electrons that affect the growth of C. acnes through flavin-mediated electron transfer and alleviate the resultant inflammatory response. Our findings demonstrate that probiotics separated from natural substances and antimicrobial methods of generating electrical energy through carbon source fermentation can help in the treatment of bacterial infections.

A smart nanoplatform for enhanced photo-ferrotherapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Emerging therapies, such as ferroptosis mediated cancer therapy and phototherapy, offer new opportunities for HCC treatment. The combination of multiple treatments is often more effective than monotherapy, but many of the current treatments are prone to serious side effects, resulting in a serious decline in patients' quality of life. Therefore, the combination therapy of tumor in situ controllable activation will improve the efficacy and reduce side effects for precise treatment of tumor. Herein, we synthesized a GSH-activatable nanomedicine to synergize photothermal therapy (PTT) and ferrotherapy. We utilized a near-infrared dye SQ890 as both an iron-chelating and a photothermal converter agent, which was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG), to attain the biocompatible SQ890@Fe nanoparticles (NPs). In the tumor microenvironment (TME), SQ890@Fe NPs showed a GSH-activated photothermal effect that could increase the Fenton reaction rate. Meanwhile, the depletion of GSH could further increase ferroptosis effect. In turn, the increasing radical generated by ferrotherapy could impair the formation of heat shock proteins (HSPs) which could amplify PTT effects by limiting the self-protection mechanism. Overall, the intelligent nanomedicine SQ890@Fe NPs combines ferrotherapy and PTT to enhance the efficacy and safety of cancer treatment through the mutual promotion of the two treatment mechanisms, providing a new dimension for tumor combination therapy.

Macrophage polarization regulates intervertebral disc degeneration by modulating cell proliferation, inflammation mediator secretion, and extracellular matrix metabolism.

Macrophage infiltration and polarization have been increasingly observed in intervertebral disc (IVD) degeneration (IDD). However, their biological roles in IDD are still unrevealed. We harvested conditioned media (CM) derived from a spectrum of macrophages induced from THP-1 cells, and examined how they affect nucleus pulposus cells (NPCs) in vitro, by studying cell proliferation, extracellular matrix (ECM) synthesis, and pro-inflammation expression; and in vivo by injection CM in a rat IDD model. Then, high-throughput sequencing was used to detect differentially expressed genes (DEGs). Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks were used to further analysis. Higher CCR7+ (M1 marker) and CD206+ (M2 marker) cell counts were found in the degenerated human IVD tissues as compared with the control. Furthermore, the cell co-culture model showed M1CM attenuated NPC proliferation, downregulated the expression of ECM anabolic genes encoding aggrecan and collagen IIα1, upregulated the expression of ECM catabolic genes encoding MMP-13, and inflammation-related genes encoding IL-1ß, IL-6, and IL-12, while M2CM showed contrasting trends. In IDD model, higher histological scores and lower disc height index were found following M1CM treatment, while M2CM exhibited opposite results. M1CM injection decreased ECM anabolic and increased ECM catabolic, as well as the upregulation of inflammation-related genes after 8 weeks treatment, while M2CM slowed down these trends. Finally, a total of 637 upregulated and 655 downregulated genes were detected in M1CM treated NPCs, and 975 upregulated genes and 930 downregulated genes in the M2CM groups. The top 30 GO terms were shown and the most significant KEGG pathway was cell cycle in both groups. Based on the PPI analysis, the five most significant hub genes were PLK1, KIF20A, RRM2, CDC20, and UBE2C in the M1CM groups and RRM2, CCNB1, CDC20, PLK1, and UBE2C in the M2CM groups. In conclusion, macrophage polarization exhibited diverse roles in IDD progression, with M1CM exacerbating cell proliferation suppression and IVD degeneration, while M2CM attenuated IDD development. These findings may facilitate the further elucidation of the role of macrophage polarization in IDD, and provide novel insights into the therapeutic potential of macrophages.