Enhancement of nitrogen on core taxa recruitment by Penicillium oxalicum stimulated microbially-driven soil formation in bauxite residue.

Microbially-driven soil formation process is an emerging technology for the ecological rehabilitation of alkaline tailings. However, the dominant microorganisms and their specific roles in soil formation processes remain unknown. Herein, a 1-year field-scale experiment was applied to demonstrate the effect of nitrogen input on the structure and function of the microbiome in alkaline bauxite residue. Results showed that the contents of nutrient components were increased with Penicillium oxalicum (P. oxalicum) incorporation, as indicated by the increasing of carbon and nitrogen mineralization and enzyme metabolic efficiency. Specifically, the increasing enzyme metabolic efficiency was associated with nitrogen input, which shaped the microbial nutrient acquisition strategy. Subsequently, we evidenced that P. oxalicum played a significant role in shaping the assemblages of core bacterial taxa and influencing ecological functioning through intra- and cross-kingdom network analysis. Furthermore, a recruitment experiment indicated that nitrogen enhanced the enrichment of core microbiota (Nitrosomonas, Bacillus, Pseudomonas, and Saccharomyces) and may provide benefits to fungal community bio-diversity and microbial network stability. Collectively, these results demonstrated nitrogen-based coexistence patterns among P. oxalicum and microbiome and revealed P. oxalicum-mediated nutrient dynamics and ecophysiological adaptations in alkaline microhabitats. It will aid in promoting soil formation and ecological rehabilitation of bauxite residue. ENVIRONMENT IMPLICATION: Bauxite residue is a highly alkaline solid waste generated during the Bayer process for producing alumina. Attempting to transform bauxite residue into a stable soil-like substrate using low-cost microbial resources is a highly promising engineering. However, the dominant microorganisms and their specific roles in soil formation processes remain unknown. In this study, we evidenced the nitrogen-based coexistence patterns among Penicillium oxalicum and microbiome and revealed Penicillium oxalicum-mediated nutrient dynamics and ecophysiological adaptations in alkaline microhabitats. This study can improve the understanding of core microbes' assemblies that affect the microbiome physiological traits in soil formation processes.

[Integrated Analysis of Soil Organic Matter Molecular Composition Changes Under Different Land Uses].

The application of biomarkers to study the molecular composition of soil organic matter (SOM) can be used to analyze the source and degradation of SOM and reveal the stability mechanism of soil organic carbon (SOC) at the molecular level. In order to further clarify the effects of different land use patterns (farmland, grassland, and forest) on the molecular composition of SOM, the changes in molecular composition of organic matter (free lipids, cutin, suberin, and lignin) on a global scale were studied using a meta-analysis method. The results showed that there were significant differences in the molecular composition of organic matter under different land use patterns. The contents of free lipids (n-alkanes, n-alkanols, n-alkanoic acids, and cyclic lipids), cutin, and lignin phenols in forest soil were significantly higher than those in grassland and farmland. There was no significant difference in the content of suberin between grassland and forest soil. The ratio of suberin to cutin in grassland was the highest, with an average of 2.96, and the averages of farmland and forest were 1.68 and 2.21, respectively. The ratio of syringic acid to syringaldehyde (Ad/Al)S and the ratio of vanillic acid to vanillin (Ad/Al)V of farmland soil were the largest, which were 1.25 and 1.58, respectively, and were significantly higher than those in grassland (0.46 and 0.69) and forest (0.78 and 0.7). The results of correlation analysis showed that in farmland soil, suberin was significantly correlated with mean annual precipitation (MAP) and clay; cutin was significantly correlated with clay; and lignin was significantly correlated with mean annual temperature (MAT), MAP, sand, and bulk density. In grassland soil, total free lipids were significantly correlated with MAP and bulk density; suberin and cutin were significantly correlated with MAT and MAP; and lignin was significantly correlated with MAP, pH, sand, and bulk density. However, only lignin was significantly correlated with MAP and sand in forest soils. Overall, the contents of SOC and molecular components in forest soil were higher under the three land use practices, and the contribution of plant roots to SOM in grassland soil was greater. In farmland soil, the degradation of lignin was accelerated due to human farming activities. Future research should focus on the regulation of soil physicochemical properties and climatic conditions on the molecular composition of SOM.

Natural history of craniovertebral abnormalities in a single-center study in 54 patients with Hurler syndrome.

OBJECTIVE: Craniovertebral junction (CVJ) abnormalities are common and well documented in mucopolysaccharidosis type I-Hurler syndrome (MPS IH), often causing severe spinal canal narrowing. However, the requirement for surgical decompression and/or fusion is uncommon. Although hematopoietic cell transplant (HCT) has been shown to prolong the lives of patients with MPS IH, its effect in halting or reversing musculoskeletal abnormalities is less clear. Unfortunately, there are currently no universal guidelines for imaging or indication for surgical interventions in these patients. The goal of this study was to track the progression of the CVJ anatomy in patients with MPS IH following HCT, and to examine radiographic features in patients who needed surgical intervention. METHODS: Patients with MPS IH treated at the University of Minnesota with allogeneic HCT between 2008 and 2020 were retrospectively reviewed. Patients who underwent CVJ surgery were identified with chart review. All MPS IH cervical scans were examined, and the odontoid retroflexion angle, clivoaxial angle (CXA), canal width, and Grabb-Oakes distance (pB-C2) were measured yearly for up to 7 years after HCT. Longitudinal models based on the measurements were made. An intraclass correlation coefficient was used to measure interrater reliability. Nine children without MPS IH were examined for control CVJ measurements. RESULTS: A total of 253 cervical spine MRI scans were reviewed in 54 patients with MPS IH. Only 4 (7.4%) patients in the study cohort required surgery. Three of them had posterior fossa and C1 decompression, and 1 had a C1-2 fusion. There was no statistically significant difference in the spinal parameters that were examined between surgery and nonsurgery groups. Among the measurements, canal width and CXA varied drastically in patients with different neck positions. Odontoid retroflexion angle and CXA tended to decrease with age. Canal width and pB-C2 tended to increase with age. CONCLUSIONS: Based on the data, the authors observed an increase in canal width and pB-C2, whereas the CXA and odontoid retroflexion angle became more acute as the patients aged after HCT. The longitudinal models derived from these data mirrored the development in children without MPS IH. Spinal measurements obtained on MR images alone are not sufficient in identifying patients who require surgical intervention. Symptom monitoring and clinical examination, as well as pathological spinal cord changes on MRI, are more crucial in assessing the need for surgery than is obtaining serial imaging.

Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway.

BACKGROUND: Melanogenesis is the process of melanin maturation which not only protects skin from UV radiation but also plays an important role in antigenicity of melanomas. Imiquimod (IMQ) is a toll-like receptor 7 (TLR7) agonist that exhibits antiviral and anticancer activity. OBJECTIVE: To explore whether IMQ could induce melanogenesis in melanoma cells. METHODS: The mouse melanoma cell line B16F10, the mouse immortalized melanocyte Melan-A, and human melanoma cell lines MNT-1, C32 and A375 were utilized in this study. The pigmented level was observed by the centrifuged cell pellet. The intracellular and extracellular melanin levels were examined in the absorbance in NaOH-extracted cell lysate and cell-cultured medium, respectively. The expression of melanogenesis related proteins was examined by immunoblotting. The intracellular cyclic AMP amount was evaluated by the cAMP Glo assay kit. The activity of phosphodiesterase 4B (PDE4B) was investigated by CREB reporter assay with overexpressed PDE4B or not. RESULTS: We demonstrated that a low dose of IMQ could trigger melanogenesis in B16F10 cells. IMQ induced microphthalmia-associated transcription factor (MITF) nuclear translocation, upregulated the expression of melanogenesis-related proteins, increased tyrosinase (TYR) activity, and led to pigmentation in B16F10 cells. Next, we found that IMQ-induced melanogenesis was activated by excessive intracellular cAMP accumulation, which was regulated through IMQ-mediated PDE4B inhibition. Finally, IMQ-induced ROS production was found to be involved in melanogenesis by its control of PDE4B activity. CONCLUSIONS: Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.

Comparison of senhance and da vinci robotic radical prostatectomy: short-term outcomes, learning curve, and cost analysis.

BACKGROUND: The Senhance® Robotic System is a new laparoscopy-based platform that has been increasingly used in radical prostatectomy (RP) procedures. The purpose of this study is to compare the outcome of Senhance RP (SRP) with da Vinci RP (DRP) cases. METHODS: From August 2019 to April 2022, we prospectively recruited 63 cases of SRP. We compared the perioperative data, postoperative complication rates, short-term surgical outcomes (3-month postoperative undetectable prostate-specific antigen (PSA) and incontinence rates), learning curves, and cost analysis with data from 63 matched da Vinci Xi RP cases. RESULTS: There was no difference in BL (180 versus 180 ml, p = 0.86) and postoperative surgical complication rate (Clavient -Dindo grade I-IV, 25.3 versus 22.2%, p = 0.21) between the SRP cases and the DRP. Regarding the oncologic and continence function, there was no difference between positive margin rate (36.5% versus 41.3%, p = 0.58), rate of undetectable PSA level at postoperative 3 months (68.3 versus 66.7%, p = 0.85), and incontinence rate (14.3 versus 15.9%, p = 1.0) at postoperative 3 months between the two cohorts. The learning curve showed a quick downward slope for laparoscopic experienced surgeons. The median pocket cost for SRP patients in our hospital was $4170, which was lower than $7675 for the DRP patients. CONCLUSIONS: Safety and short-term outcomes are comparable between SRP and DRP. For experienced LRP surgeons, using the Senhance system to perform RP is straightforward. With a more affordable price as its biggest advantage, the Senhance system may serve as a safe and effective alternative for robotic RP.

Bilateral orbital dermoid cysts: A case report.

Dermoid cysts are one of the most common benign orbital tumours in children and usually occur unilaterally. Bilateral dermoid cysts in the orbit are rare. We report here, a case of bilateral orbital dermoid cysts, in a 29-month-old baby girl. The patient's prognosis was favourable following surgical resection. Through this case report, we hope to increase the recognition and understanding of this condition.

Diffuse CNS cortical vein malformations with chromosome 17q microduplication: Possible link to SEC14L1.

Partial trisomy of the long arm of chromosome 17 (17q) is a rare but clinically recognized syndrome that involves facial dysmorphisms, skeletal abnormalities, and global developmental delay, as well as various reports of cardiovascular, renal, and central nervous system abnormalities. This report presents a novel neuroradiologic finding of diffuse enlarged, tortuous cortical veins with physiological antegrade flow in a child with a microduplication of the distal end of 17q. To our knowledge, this finding has not been described previously. Although the exact cause for the cortical vascular anomaly is currently unknown, this duplicated region contains genes of interest for future studies that focus on normal and abnormal angiogenesis.

Airway Management of an Infant With Giant Neck Macro-Cystic Hygroma Utilizing a High-Flow Nasal Cannula.

BACKGROUND:  Cystic hygroma is a congenital lymphatic malformation. It may present as a huge mass in the neck, jeopardizing airway patency and prolonging intubation time, resulting in hypoventilation and hypoxemia. We used a high-flow nasal cannula to decrease the risk of hypoxemia and provide anesthesiologists sufficient time to perform tracheal intubation in young infants. CASE PRESENTATION: A 33-day-old infant (height, 55 cm; weight, 5.05 kg) was diagnosed with macro-cystic hygroma of the right neck. Considering the progressive enlargement of the macrocystic hygroma and its impact on the airway, urgent intervention becomes imperative. Among the available treatment modalities, percutaneous cyst aspiration and sclerotherapy performed under ultrasound guidance represent the most commonly chosen approach. During the induction of general anesthesia, the otolaryngologists were on standby and prepared for emergency tracheotomy. The anesthesiologists chose total intravenous anesthesia induction while maintaining spontaneous breathing. A high-flow nasal cannula was used to keep the infant oxygenated, and endotracheal intubation was successfully performed using a C-MAC video laryngoscope and fiber-optic bronchoscope. CONCLUSIONS: Airway management is the biggest challenge for anesthesiologists when delivering general anesthesia to infants with neck macro-cystic hygroma. Total intravenous anesthesia could be a choice for induction without considering compromised respiration and the side effects of inhalational anesthetics. A high-flow nasal cannula can be used in young infants to maintain oxygenation and allow anesthesiologists a longer time to perform intubation.

Microstructural and hemodynamic changes in the fundus after pars plana vitrectomy for different vitreoretinal diseases.

BACKGROUND: Pars plana vitrectomy is the standard treatment for several vitreoretinal diseases. Continuous improvements in ophthalmic surgical techniques have led to excellent postoperative recovery of the anatomic structure of the fundus. However, postoperative visual outcomes are not always satisfactory. METHODS: A literature search of articles published before 31 December 2022 was conducted on PubMed using the following keywords: "diabetic retinopathy," "rhegmatogenous retinal detachment," "idiopathic epiretinal membrane," "idiopathic macular hole," "vitrectomy," "optical coherence tomography," "optical coherence tomography angiography," "microstructure," "microstructural," "hemodynamic," "hemodynamics," and "microcirculation." Additional studies were identified by hand-searching references for relevant studies. Articles were screened for language, repetition, and relevance to the direction of study. Studies with a sample size ≥ 7 and the final follow-up time ≥ 4 weeks after vitrectomy were included in this review. Only articles published in English were included. Articles not related to our topic were excluded. Reviews and single case reports were excluded. We structured this review by disease category. The thickness of the retina and choroid, the area of the foveal avascular zone, the vessel density of the retinal and choroidal capillary plexus, and the potential association of related parameters with postoperative visual outcomes are the main outcome measures of studies included in this review. RESULTS: A total of 48 studies were included in this review. There were contradictory results regarding the association between postoperative microcirculatory parameters and visual acuity in patients with diabetic macular edema, with some studies concluding that improvement in perimacular microcirculation may be an important factor that affects visual acuity, and others concluded that postoperative improvement in visual acuity was not related to changes in macular blood flow. The results of studies on the relationship between postoperative microstructural and microcirculatory parameters and visual acuity in rhegmatogenous retinal detachment, idiopathic epiretinal membrane, and idiopathic macular hole eyes have been inconsistent. In gas tamponade macula-off rhegmatogenous retinal detachment eyes, postoperative best-corrected visual acuity has been reported to correlate positively with vessel density of deep capillary plexus and negatively with foveal avascular zone area of superficial capillary plexus and deep capillary plexus. In silicone oil tamponade macula-off rhegmatogenous retinal detachment eyes, best-corrected visual acuity has been reported to be positively correlated with the retinal thickness of the parafoveal 3 mm temporal quadrant and positively correlated with the vessel density of the superficial capillary plexus in the foveal, parafoveal, and perifoveal area. In addition, best-corrected visual acuity was worse and associated with reduced thickness of the inner retina, ganglion cell layer, outer plexiform layer, and outer nuclear layer in silicone oil tamponade rhegmatogenous retinal detachment eyes compared to gas tamponade. Postoperative best-corrected visual acuity in idiopathic epiretinal membrane eyes was positively correlated with the foveal avascular zone area but negatively correlated with full retinal thickness and inner retinal thickness in the foveal and parafoveal areas. Improvement in postoperative best-corrected visual acuity in idiopathic macular hole eyes was associated with reduced inner retinal thickness and reduced foveal avascular zone area. CONCLUSIONS: Microstructural and hemodynamic changes are involved in the recovery process after PPV for different vitreoretinal diseases. The thickness of each retinal layer in different regions of the macula, foveal avascular zone area, and vessel density of different retinal capillary plexuses in different macular regions may be potential prognostic factors for postoperative visual recovery. However, the results of the existing literature are inconsistent and require further study.

A pH-responsive supramolecular hydrogel encapsulating a CuMnS nanoenzyme catalyst for synergistic photothermal-photodynamic-chemodynamic therapy of tumours.

Traditional cancer therapies no longer meet the current demand for cancer precision therapy and personalized treatment and it's essential to develop new therapeutic modalities as well as to investigate new combination anti-tumor mechanisms. Therefore, amphiphilic prodrug polymer chains linking methoxy poly(ethylene glycol) (mPEG) and cinnamaldehyde (CA) with adipic acid dihydrazide (ADH) as the pH-responsive center were designed and synthesized, which could self-assemble into PAC micelles in aqueous solution. A supramolecular hydrogel was formed based on the host-guest interaction between α-cyclodextrin (α-CD) and PAC micelles. Polyetherimide (PEI) modified copper manganese sulfide nanoenzyme catalysts (PCMS NPs) were prepared by a solvothermal method, which could be uniformly dispersed in the hydrogel to form a composite supramolecular hydrogel (PCMS@PAC/α-CD Gel). Under an acidic tumor environment, pH-responsive hydrazone bonds were broken, resulting in the slow release of CA and the amplification of hydrogen peroxide (H2O2) levels. PCMS NPs exerted peroxidase (POD)-like activity and catalase (CAT)-like activity, which could convert H2O2 into hydroxyl radicals (˙OH) and oxygen (O2) to alleviate intra-tumor hypoxia and induce apoptosis, while exerting glutathione oxidase (GPX)-like activity to consume glutathione (GSH) to further enhance the effect of chemodynamic therapy (CDT). Under near-infrared light (NIR) irradiation, PCMS NPs exhibited an excellent photothermal conversion performance, which could rapidly increase the temperature of tumor cells to above 42 °C for photothermal therapy (PTT) and convert O2 to a superoxide anion (˙O2-) by exerting oxidase (OXD)-like activity for photodynamic therapy (PDT). It was demonstrated by in vitro and in vivo experiments that the PCMS@PAC/α-CD Gel was highly cytotoxic to cancer cells and could effectively inhibit tumor growth, indicating the potential for applications in the fields of biomedicine and smart materials.

Comparative biotic and abiotic effects on greenhouse gas emissions from agricultural ecosystems: application of straw or biochar?

Farmland has become a significant contributor to greenhouse gas (GHG) emissions, and research has shown that the addition of straw or biochar may be a viable method for mitigating these emissions. However, there is a lack of understanding regarding the comparative biotic and abiotic effects of straw and biochar amendments on GHG emissions. To address this knowledge gap, we conducted a meta-analysis of 100 published papers to quantify the impact of straw and biochar application on GHG emissions. Our findings indicate that straw application significantly increased CO2 and CH4 emissions from agricultural ecosystems by 46.2% and 113.5%, respectively, but did not have a significant effect on N2O emissions. Conversely, biochar amendment significantly reduced CO2, CH4, and N2O emissions by an average of 11.0%, 31.7%, and 22.8%, respectively. We also found that straw and biochar amendments increased soil pH, soil organic carbon (SOC), and C/N ratio, and there were significant differences between them. Moreover, straw application significantly increased the microbial biomass carbon (MBC) content and microbial quotient by 37.1% and 20.1%, respectively, while biochar application increased the MBC content by 25.0% without a significant effect on the microbial quotient. Furthermore, both straw and biochar applications promoted the nitrification process and increased the abundance of ammonia-oxidizing bacteria (AOB) by 50.7% with straw and by 57.5% and 75.1% with biochar for ammonia-oxidizing archaea (AOA) and AOB, respectively. The denitrification process was also stimulated by straw or biochar amendment, resulting in an increase in the abundance of nirK by 22.9% and 16.8%, respectively. Biochar amendment additionally increased the abundance of nosZ by 29.4%, indicating that the main reason for reducing N2O emissions through biochar application is the conversion of NO3--N to N2. Thus, compared to straw application, biochar application is a more effective method for reducing greenhouse gas emissions.

Venous Sinus Stenosis with Prominent Emissary Veins: A New Common Cranial MRI Finding of Mucopolysaccharidosis I.

Mucopolysaccharidosis I-Hurler (MPSIH) syndrome is the most severe form of a group of hereditary lysosomal diseases. This study aims to describe previously unreported common cranial findings of sigmoid sinus stenosis with prominent emissary veins in MPSIH. A retrospective review was conducted of 66 patients with MPSIH who were treated at our institution. A total of 12 cranial MR imaging studies from 12 different patients demonstrating the venous sinus anatomy were reviewed. All 12 patients exhibited various degrees of sigmoid or transverse sinus stenosis. Eleven had various forms of emissary veins. Of those 12 patients with imaging of the venous sinuses, 9 had a lumbar puncture within the same months as the acquisition of the venogram without any correlation between elevated opening pressure and the severity of the venous sinus stenosis. Stenotic cerebral venous sinuses with associated emissary veins, common in patients with MPSIH, may be abnormal findings due to posterior fossa horns from glycosaminoglycan depositions rather than signs of elevated intracracranial pressure or requirement of CSF diversion.

Atonal homolog 7 (ATOH7) confers neuroprotection for photoreceptor cells in glaucoma via inhibition of the notch pathway.

Single-cell RNA sequencing (scRNA-seq) technologies enable the profiling and analysis of the transcriptomes of single cells and hold promise for clarifying gene mechanisms at single-cell resolution. We based this study on scRNA-seq data to reveal glaucoma-related genes and downstream pathways with neuroprotection effects. The scRNA-seq datasets related to glaucoma of retinal tissue samples of human beings and Atonal Homolog 7 (ATOH7)-null mice were obtained from the GEO database. The 74 top marker genes and 20 cell clusters were obtained in human retinal tissue samples. The key gene ATOH7 was found after the intersection with genes from GeneCards data. In the ATOH7-null mouse retinal tissue samples, pseudotime inference demonstrated significant changes in cell differentiation. Moreover, mouse retinal photoreceptor cells (PRCs) were cultured and treated with lentivirus carrying oe-ATOH7 alone or in combination with Notch signaling pathway activator Jagged-1/FC, after which cell biological functions were determined. The involvement of ATOH7 in glaucoma was identified through regulating PRCs. Furthermore, ATOH7 conferred neuroprotection in PRCs in glaucoma by mediating the Notch signaling pathway. In vitro data confirmed that ATOH7 overexpression promoted the differentiation of PRCs and inhibited their apoptosis by suppressing the Notch signaling pathway. The evidence provided by our study highlighted the involvement of ATOH7 in the blockade of the Notch signaling pathway, resulting in the neuroprotection for PRCs in glaucoma.

Microcystic adnexal carcinoma of the eyelid and orbit: A case report and review of literature.

Microcystic adnexal carcinoma (MAC), a rare and low-grade malignant skin tumor, is characterized by a high rate of misdiagnosis and a preponderance for local recurrence, but seldom seen nodal or distant metastasis. Although MAC typically occurs almost in the head and neck region, primary eyelid or orbital MAC is very rare. To explore the unique characteristics of the eyelid and orbital MAC, we reviewed the relevant literature. Based on its distinctive anatomical location and the aggressive behavior, eyelid or orbital MAC not only exhibit a high rate of misdiagnosis and local recurrence, but also lead to serious complications such as disfigurement after orbital exenteration, paranasal sinuses or intracranial invasion, even death. Misdiagnosis of MAC commonly result from its rarity and nonspecific clinical and histopathological presentation. To reduce or avoid misdiagnosis, it is important to increase awareness for MAC and obtain a full-thickness biopsy specimen in histopathological analysis. Due to its extensive invasive growth pattern, MAC has a high rate of local recurrence, so complete excision with clear margins and long-term follow-up of patients with MAC are necessary. About those serious complications of the eyelid and orbital MAC, early and accurate diagnosis, complete excision is very important. Moreover, an interprofessional team consisting of ophthalmologist, otolaryngologist, neurologist, dermatologist, pathologist, radiologist is needed to evaluate and treat this disease. In summary, increasing awareness, early and accurate diagnosis, complete excision, long-term follow-up, and a multidisciplinary team is crucial for management of the eyelid and orbital MAC.

High-Throughput Sequencing Data Reveal an Antiangiogenic Role of HNF4A-Mediated CACNA1A/VEGFA Axis in Proliferative Diabetic Retinopathy.

Purpose: Proliferative diabetic retinopathy (PDR) is characterized by retinal new vessel formation, pointing to the importance of the antiangiogenic treatment in PDR. Hepatocyte nuclear factor 4A (HNF4A) has been highlighted to inhibit vascular endothelial growth factor (VEGF)-stimulated in vitro angiogenesis. Therefore, this study aims to elucidate the potential antiangiogenic mechanisms of HNF4A in PDR. Methods: PDR-related high-throughput sequencing datasets (GSE94019, GSE102485, and GSE191210) were obtained from the Gene Expression Omnibus (GEO) database, followed by the screening of differentially expressed genes (DEGs). The protein-protein interaction (PPI) network of the candidate DEGs was constructed based on gene set enrichment analysis (GSEA) data and Search Tool for the Retrieval of Interacting Genes (STRING) data. In addition, the key genes and pathways related to angiogenesis were screened by functional enrichment analysis. Furthermore, human retinal microvascular cells were used for further in vitro validation. Results: Four key genes (CACNA1A, CACNA1E, PDE1B, and CHRM3) related to PDR were identified in the grey module. CACNA1A affected angiogenesis in PDR by regulating vascular endothelial growth factor A (VEGFA) expression. Furthermore, HNF4A participated in angiogenesis in PDR by activating CACNA1A. In vitro experiments further identified that inhibition of HNF4A reduced CACNA1A expression and increased VEGFA expression, thus promoting angiogenesis in PDR. Conclusions: In conclusion, the obtained findings suggest that antiangiogenic HNF4A activates the CACNA1A/VEGFA axis in PDR. Our work provides new insights into the angiogenic mechanism of PDR and offers potential targets for translational applications.

Survival outcomes and prognostic factors for first-line abiraterone acetate or enzalutamide in patients with metastatic castration-resistant prostate cancer.

PURPOSE: To investigate the survival outcomes of metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line novel androgen receptor axis-targeted therapies (ARATs) and prognostic factors for patient survival. METHODS: This retrospective study obtained data from 202 patients who started abiraterone acetate or enzalutamide as first-line therapy for mCRPC between 2016 and 2021 from a single academic center. The primary endpoint was overall survival (OS) defined as the interval from the start of ARAT to death, loss to follow-up, or the end of the study period. The secondary endpoints were PSA decline, PSA nadir, and time to nadir (TTN) after ARATs. Kaplan-Meier survival analyses were applied for depicting OS. Cox proportional hazards model with inversed probability of treatment weighing-adjustment was used to validate the effect of patient, disease, and treatment response factors on OS. RESULTS: Among 202 patients, 164 patients were treated with first-line ARATs alone and 38 patients received second-line chemotherapy. The median OS was not reached in patients with first-line ARATs alone and was 38.8 months in those with subsequent chemotherapy after failure from ARATs. OS was not different between the use of abiraterone and enzalutamide, though enzalutamide showed a higher rate of PSA decline ≧ 90% (56% versus 40%, p = 0.021) and longer TTN (5.5 versus 4.7 months, p = 0.019). Multivariable analysis showed that PSA nadir > 2 ng/mL [hazard ratio (HR) 7.04, p < 0.001] and TTN<7 months (HR 2.18, p = 0.012) were independently associated with shorter OS. Patients with both of these poor prognostic factors had worse OS compared to those who had 0-1 factors (HR 9.21, p < 0.001). CONCLUSIONS: Patients with mCRPC who received first-line ARATs had better survival if they had a PSA nadir[Formula: see text]2 ng/mL or a TTN[Formula: see text]7 months. Further study is needed to determine if an early switch in therapy for those in whom neither is achieved may impact OS.

'Diagnostic anchoring' and a delayed diagnosis of reversible cerebral vasoconstriction syndrome.

We present a case of a woman in her 60s with acute left hemispheric ischaemic stroke syndrome due to tandem occlusions of the proximal left internal carotid artery and left middle cerebral artery. This was treated with emergent carotid artery stenting and endovascular clot retrieval. The patient made a complete recovery and was discharged home only to represent a few days later with focal neurological symptoms, profound headache and labile blood pressure. The diagnostic and management challenges of reversible cerebral vasoconstriction syndrome, including imaging assessment and the importance of avoiding 'diagnostic anchoring' are discussed.

Long-term weathering difference in soil-like indicators of bauxite residue mediates the multifunctionality driven by microbial communities.

Long-term weathering enhances the stability of ecosystem services and alters the microbiome, however, its influences on the relationship between microbial diversity and multifunctionality are still poorly understood. Hereby, 156 samples (0-20 cm) from five artificially divided functional zones including central bauxite residue zone (BR), the zone near residential area (RA), the zone near dry farming area (DR), the zone near natural forest area (NF), and the zone near grassland and forest area (GF) were collected in a typical disposal area to determine the heterogeneity and development of biotic and abiotic properties of bauxite residue. Residues in BR and RA exhibited higher values of pH, EC, heavy metals, and exchangeable sodium percentage compared to those in NF and GF. Our results showed a positive correlation between multifunctionality and soil-like quality during long-term weathering. Microbial diversity and microbial network complexity responded positively to multifunctionality within the microbial community, which was parallel with ecosystem functioning. Long-term weathering promoted oligotrophs-dominated bacterial assemblages (mostly Acidobacteria and Chloroflexi) and suppressed copiotrophs (including Proteobacteria and Bacteroidota), while the response of fungal communities was lower. Rare taxa from bacterial oligotrophs were particularly important at the current stage for maintaining ecosystem services and ensuring microbial network complexity. Our results underscore the significance of microbial ecophysiological strategies in response to changes in multifunctionality during long-term weathering, and highlight the necessity of conserving and augmenting the abundance of rare taxa to ensure the stable provision of ecosystem functions in bauxite residue disposal areas.

Increased pituitary volumes in patients with Sanfilippo syndrome (mucopolysaccharidosis type 3, MPS III).

PURPOSE: To evaluate apparent pituitary gland enlargement in patients with Sanfilippo syndrome observed at our institution. METHODS: Twelve patients with Sanfilippo syndrome with brain MRI were studied. Anterior, posterior, and whole pituitary volumes were estimated using the prolate ellipsoid volume calculation method (π/6 × L × W × H). Convexity along the upper pituitary margin (Elster's grade) was also measured. These values were compared to two age- and sex-matched groups (normal controls and patients with Hurler syndrome) using one-way ANOVA followed by Tukey's post hoc analysis for multiple comparisons. RESULTS: In the Sanfilippo cohort, the mean whole pituitary volume was 529.9 mm, the mean anterior pituitary volume was 333.4 mm, and the mean posterior pituitary volume was 59.1 mm with Elster's grade of 4.2. In the control cohort, the mean whole pituitary volume was 217.4 mm, the mean anterior pituitary volume was 154.8 mm, and the mean posterior pituitary volume was 28.4 mm with Elster's grade of 2.5. In the Hurler syndrome cohort, the mean whole pituitary volume was 310.0 mm, the mean anterior pituitary volume was 178.2 mm, and the mean posterior pituitary volume was 35.4 mm with Elster's grade of 3.5. CONCLUSION: In our cohort of patients with Sanfilippo syndrome, whole, anterior, and posterior pituitary volumes and degree of convexity along the upper pituitary border were all significantly greater than controls. The cause of these morphological changes is unclear, as is clinical correlation of the findings.

In situ injectable NIR-responsive supramolecular hydrogels encapsulating ROS-triggered chain-breakage prodrug micelles and hydrophilic Fe3O4 nanoparticles for enhanced synergistic chemo-photothermal therapy.

Efficient synergistic therapeutic strategies for tumors with high specificity and sensitivity remain a major challenge. An injectable near-infrared (NIR)-responsive supramolecular hydrogel was prepared via host-guest interactions between conjugated poly(N-phenylglycine)-poly(ethylene glycol) (PNPG-PEG) and α-cyclodextrin. A reactive oxygen species (ROS)-triggered chain-breakage prodrug was composed of a thioketal (TK) linkage of methoxy poly(ethylene glycol) (mPEG) and doxorubicin (DOX). The resulting amphiphilic conjugate mPEG-TK-DOX can self-assemble into prodrug micelles. PEG/poly(etherimide) (PEI)@Fe3O4 nanoparticles (PEG/PEI@Fe3O4 NPs) were prepared using a thermal decomposition method. The prodrug micelles and PEG/PEI@Fe3O4 NPs can be well dispersed into the hydrogel system. In a tumor micro-acid environment, PEG/PEI@Fe3O4 NPs catalyze the decomposition of H2O2 to highly toxic ˙OH via a Fenton reaction to induce the breakage of ROS-responsive TK bonds for the dissociation of micelles and the continuous release of DOX. PEG/PEI@Fe3O4 NPs can also generate an NIR-thermal effect and enhance the photothermal therapy. Notably, by combining with controllable photothermal therapy, the in situ composite hydrogel system shows enhanced synergistic chemo-photothermal therapy for tumors and almost complete in vitro and in vivo tumor suppression, providing a promising synergistic tumor treatment strategy.