Mechanism of aroma formation in white tea treated with solar withering.

Withering is a crucial process that determines the quality of white tea (WT). Solar withering (SW) is reported to contribute to the aroma quality of WT. However, the mechanism by which aroma is formed in WT subjected to SW remains unclear. In this study, through headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and transcriptomics, we found that 13 key genes enriched in the mevalonic acid and methylerythritol phosphate pathways, such as those of 1-deoxy-D-xylulose-5-phosphate synthase and terpineol synthase, were significantly upregulated, promoting the accumulation of α-terpinolene, geraniol, and nerolidol, which imparted floral and fruity odors to WT subjected to SW. Additionally, the significant upregulation of lipoxygenases enriched in the lipoxygenase pathway promoting the accumulation of hexanol, 1-octen-3-ol, (E, Z)-3,6-nonadien-1-ol, and nonanal, which contributed to the green and fresh odor in WT subjected to SW. This study provided the first comprehensive insight into the effect mechanism of SW on aroma formation in WT.

2.5D deep learning based on multi-parameter MRI to differentiate primary lung cancer pathological subtypes in patients with brain metastases.

BACKGROUND: Brain metastases (BMs) represents a severe neurological complication stemming from cancers originating from various sources. It is a highly challenging clinical task to accurately distinguish the pathological subtypes of brain metastatic tumors from lung cancer (LC).The utility of 2.5-dimensional (2.5D) deep learning (DL) in distinguishing pathological subtypes of LC with BMs is yet to be determined. METHODS: A total of 250 patients were included in this retrospective study, divided in a 7:3 ratio into training set (N=175) and testing set (N=75). We devised a method to assemble a series of two-dimensional (2D) images by extracting adjacent slices from a central slice in both superior-inferior and anterior-posterior directions to form a 2.5D dataset. Multi-Instance learning (MIL) is a weakly supervised learning method that organizes training instances into "bags" and provides labels for entire bags, with the purpose of learning a classifier based on the labeled positive and negative bags to predict the corresponding class for an unknown bag. Therefore, we employed MIL to construct a comprehensive 2.5D feature set. Then we used the single-slice as input for constructing the 2D model. DL features were extracted from these slices using the pre-trained ResNet101. All feature sets were inputted into the support vector machine (SVM) for evaluation. The diagnostic performance of the classification models were evaluated using five-fold cross-validation, with accuracy and area under the curve (AUC) metrics calculated for analysis. RESULTS: The optimal performance was obtained using the 2.5D DL model, which achieved the micro-AUC of 0.868 (95% confidence interval [CI], 0.817-0.919) and accuracy of 0.836 in the test cohort. The 2D model achieved the micro-AUC of 0.836 (95 % CI, 0.778-0.894) and accuracy of 0.827 in the test cohort. CONCLUSIONS: The proposed 2.5D DL model is feasible and effective in identifying pathological subtypes of BMs from lung cancer.

Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism.

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.

Hybrid Overlayer of Defective Ni-MOF and NiO Nanoparticles toward Efficient TiO2/CdS Type-II Heterojunction.

The severe photocorrosion of cadmium sulfide (CdS) restricts its practical application for solar hydrogen production. Although remarkable progress has been achieved with an overlayer strategy for isolating the CdS surface, the lifetime of CdS-based photoanodes is still far from the actual requirements. Herein, a hybrid overlayer of defective Ni-MOF and NiO nanoparticles has been developed through the chemical bath deposition method with postannealing. This hybrid overlayer of Ni-MOF-d is coated on the surface of the TiO2/CdS type-II heterojunction. The composite photoanode exhibits a photocurrent density of 4.41 mA cm-2 at 1.23 VRHE, which is 3.47- and 1.32-fold that of CdS and TiO2/CdS, respectively. The Ni-MOF-d overlayer gives rise to a negative shift of the onset potential by 59.51 mV. After a long-term stability test of 11 h, a photocurrent retention of 70% is observed, which is among the most robust CdS-based photoanodes. The kinetics studies reveal that the performance improvements can be attributed to the multiple functions of the Ni-MOF-d hybrid overlayer, including isolating the CdS surface from the electrolyte, cocatalyzing the electrode oxidation processes, passivating the surface defect states of CdS, and facilitating the charge injection from the photoanode to the electrolyte.

Flavonoids as therapeutic agents for epilepsy: unveiling anti-inflammatory and antioxidant pathways for novel treatments.

Epilepsy, a chronic neurological disorder affecting millions globally, is often exacerbated by neuroinflammation and oxidative stress. Existing antiepileptic drugs primarily manage symptoms, leaving the disease's progression largely unaddressed. Flavonoids, ubiquitous plant metabolites with potent anti-inflammatory and antioxidant properties, show promise in epilepsy treatment. Unlike conventional therapies, they target multiple pathophysiological processes simultaneously, offering a comprehensive approach to this complex neurological disorder. This review explores the dual role of flavonoids in mitigating neuroinflammation and reducing oxidative stress through various molecular pathways. By inhibiting key inflammatory mediators and pathways such as NF-κB, MAPK, JNK, and JAK, flavonoids offer neuronal protection. They enhance the body's natural antioxidant defenses by modulating enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase. Moreover, flavonoids influence crucial antioxidant response pathways like PI3K/AKT, Nrf2, JNK, and PKA. Despite their therapeutic promise, the low bioavailability of flavonoids poses a considerable challenge. However, cutting-edge strategies, including nanotechnology and chemical modifications, are underway to improve their bioavailability and therapeutic efficacy. These advancements support the potential of flavonoids as a valuable addition to epilepsy treatment strategies.

Occurrence, distribution, and ecological risks of antibiotics and antibiotic resistance genes in the surface waters of Gaoyou Lake, China.

This work examined the occurrence characteristics and ecological risks of 31 antibiotics across five classes and seven ARGs in the surface waters of Gaoyou Lake. A total of 27 antibiotics, spanning four classes, were detected in the surface waters of Gaoyou Lake, with an overall concentration ranging from 57.5 to 114 ng/L and an average of 78.8 ng/L. Sulfonamide antibiotics exhibited the highest average concentration at 32.7 ng/L. Spatial analysis revealed that antibiotic concentration levels in the western region of the lake were higher than those in other areas. Similarly, ARGs were most abundant in this area, with sulfonamide ARGs demonstrating a notably higher mean abundance than other ARGs. Correlation analysis revealed strong positive associations between sul1 and several antibiotics, including sulfadimidine, sulfamethoxazole, ciprofloxacin, lincomycin, clindamycin, erythromycin, and intl1 (P < 0.05), with intra-group correlations among sulfonamide ARGs exceeding those between different ARG groups. Ecological risk assessment indicated that erythromycin and sulfamethoxazole presented medium risks, whereas roxithromycin, azithromycin, and lincomycin were associated with low risks to aquatic organisms. The ecological risk proportions across monitoring sites were primarily low (10.6%) and moderate (16.7%), with no high-risk areas identified and 72.7% presenting no risk. The cumulative ecological risk quotient (RQcum) suggested a medium-risk level at all surveyed sites.

Discovery of lignans and curcuminoids as the effective inhibitors of pancreatic lipase: structure-activity relationship and inhibitory mechanism.

Pancreatic lipase (PL) is the main enzyme in the digestive system that breaks down triglyceride and promotes its absorption. In this paper, we found that lignans 2, 3 and 21, curcuminoids 24-26 exhibited significant inhibitory potential against PL. The structure-activity relationship (SAR) indicated that benzo-1, 3-dioxole group in the construction of lignans is essential to inhibitory effects against PL, while double bonds at C-7/C-2 position and 4-hydroxyphenyl moiety in the structure of curcuminoids are beneficial for PL inhibition. The kinetic studies and molecular docking were also conducted, the results showed that the three curcuminoids with the strongest inhibition effect above were all mixed inhibitors of PL. Furthermore, curcuminoids 24-26 displayed a preferential selectivity towards, in contrast to other serine hydrolases. The above results indicate that lignans and curcuminoids are natural functional components for PL inhibition, providing new ideas for finding and developing novel lead compounds for the treatment of obesity.

Hypoxia-inducible Factor 1α Contributes to Matrix Metalloproteinases 2/9 and Inflammatory Responses in Periodontitis.

Periodontitis is a prevalent condition characterized by inflammation and tissue destruction within the periodontium, with hypoxia emerging as a contributing factor to its pathogenesis. Hypoxia-inducible factor 1α (HIF-1α) has a crucial role in orchestrating adaptive responses to hypoxic microenvironments and has been implicated in various inflammatory-related diseases. Understanding the interplay between HIF-1α, matrix metalloproteinases (MMPs), and inflammatory responses in periodontitis could provide insights into its molecular mechanisms. We investigated the relationship between HIF-1α, MMP2, and MMP9 in gingival crevicular fluid (GCF) and periodontal ligament stem cells (PDLSCs) from periodontitis patients. The expression levels of HIF-1α, MMP2, MMP9, and inflammatory factors (IL-6, IL-1ß, TNF-α) were assessed using enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR). Additionally, osteogenic differentiation of PDLSCs was identified by alkaline phosphatase activity. Significantly elevated levels of HIF-1α, MMP2, and MMP9 were observed in GCF of periodontitis patients compared to controls. Positive correlations were found between HIF-1α and MMP2/MMP9, as well as with IL-6, IL-1ß, and TNF-α. Modulation of HIF-1α expression in PDLSCs revealed its involvement in MMP2/9 secretion and inflammatory responses, with inhibition of HIF-1α mitigating these effects. Furthermore, HIF-1α inhibition alleviated the reduction in osteogenic differentiation induced by inflammatory stimuli. Our findings elucidate the regulatory role of HIF-1α in MMP expression, inflammatory responses, and osteogenic differentiation in periodontitis. In conclusion, targeting HIF-1α signaling pathways may offer therapeutic opportunities for managing periodontitis and promoting periodontal tissue regeneration.

Removal of sulfonamide antibiotics by constructed wetland substrate with NaOH-modified corn straw biochar under different operating conditions.

This study examined the elimination of sulfonamide antibiotics (SAs) by constructed wetland substrates with NaOH-modified corn straw biochar and assessed the impact of environmental conditions on the effectiveness of SAs removal. The study demonstrated that the constructed wetland substrate with NaOH-modified biochar significantly eliminated eight SAs, with a removal rate of over 94 %. During the removal process, the intermediates will undergo regeneration of the parent compounds under low DO concentrations. This was based on the linear stepwise regression analysis and Geodetector models. The results showed that SA types COD, NH4+-N, TN, and DO had a stronger influence. The dominant bacteria in the constructed wetland system were mainly affected by antibiotic concentration, DO, NH4+-N and NO3--N, which affected the removal of antibiotics. Overall, the constructed wetland substrate with NaOH-modified corn straw biochar can be effectively employed as an ecological method for eliminating SAs from the environment.

Exploring the relationship between depressive symptoms, problematic smartphone use, and cumulative risk factors in nursing students: A cross sectional study.

BACKGROUND: No single risk factor is decisive in shaping an individual's healthy development. This study aimed to analyze the relationship between depressive symptoms and a cumulative risk index comprising individual, family, and social variables among nursing students. METHODS: We enrolled 1716 Chinese nursing students from three universities in a paperless survey that assessed a range of individual, family, and social risk factors associated with depressive symptoms. Multiple risk analysis was conducted to create a composite risk score for each individual. A test for trend was employed to assess the relationship between the multiple risk classification and depressive symptoms individually. Additionally, a 2-step cluster analysis and χ2 tests were used to examine the relationship between the different clusters and the level of depressive symptoms. RESULTS: The mean scores of depressive symptoms increased significantly as the number of risk factors increased, regardless of their combination. As the number of risk factors increased, the proportion of nursing students in the normal group decreased, while the proportion in the group with depressive symptoms of varying severity tended to increase (P < 0.001). A high-risk cluster characterized by poor sleep quality combined with problematic smartphone use was associated with higher levels of depressive symptoms (P < 0.001). CONCLUSION: Based on these findings that cumulative exposure to multiple risk factors is more harmful than cumulative exposure to fewer risk factors, then interventions that isolate only one risk factor are less likely to be effective than those that are multifaceted.

A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus.

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 µL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.

An exact projection pursuit-based algorithm for multivariate two-sample nonparametric testing applicable to retrospective and group sequential studies.

Nonparametric tests for equality of multivariate distributions are frequently desired in research. It is commonly required that test-procedures based on relatively small samples of vectors accurately control the corresponding Type I Error (TIE) rates. Often, in the multivariate testing, extensions of null-distribution-free univariate methods, e.g., Kolmogorov-Smirnov and Cramér-von Mises type schemes, are not exact, since their null distributions depend on underlying data distributions. The present paper extends the density-based empirical likelihood technique in order to nonparametrically approximate the most powerful test for the multivariate two-sample (MTS) problem, yielding an exact finite-sample test statistic. We rigorously apply one-to-one-mapping between the equality of vectors' distributions and the equality of distributions of relevant univariate linear projections. We establish a general algorithm that simplifies the use of projection pursuit, employing only a few of the infinitely many linear combinations of observed vectors' components. The displayed distribution-free strategy is employed in retrospective and group sequential manners. A novel MTS nonparametric procedure in the group sequential manner is proposed. The asymptotic consistency of the proposed technique is shown. Monte Carlo studies demonstrate that the proposed procedures exhibit extremely high and stable power characteristics across a variety of settings. Supplementary materials for this article are available online.

The dynamic response mechanism of crops to manganese uptake and transfer mediated by different intercropping crop attributes.

BACKGROUND: An issue of pressing concern is the manganese contamination in farmland soils adjacent to industrial areas. To address this, intercropping hyperaccumulator plants with crops emerges as a sustainable approach to ensuring food security. This study aims to investigate the influence of intercropping Sedum alfredii with maize or soybean on their growth and the dynamics of manganese accumulation through field experiments. RESULTS: The results showed that compared with monoculture, the Sedum alfredii-maize intercropping system exhibited a land equivalent ratio (LER) of 1.89, signifying a 71.13% augmentation in bioaccumulation amount (BCA). Additionally, it led to a significant reduction in manganese content in various organs, ranging from 17.05% to 25.50%. However, the Sedum alfredii-soybean intercropping system demonstrated a LER of 1.94, accompanied by a 66.11% increase in BCA, but did not significantly reduce the manganese content in the roots, stems, and pods of soybeans. Furthermore, manganese accumulation in maize and soybean grains was primarily attributed to the aboveground translocation of manganese. The intercropping effect on blocking manganese absorption of maize during growth and maturity is primarily attributed to the earlier manganese accumulation in intercropped maize by 2.63 to 4.35 days, and a reduction of 21.95% in the maximum manganese accumulation rate. CONCLUSIONS: The study found that manganese accumulation dynamics vary significantly depending on the crop family. Intercropping Sedum alfredii with maize enhances land-use efficiency and reduces manganese uptake by crops, making it a promising strategy for remediating manganese-contaminated farmland near industrial areas. © 2024 Society of Chemical Industry.

Long-term safety and influence on growth in patients receiving sirolimus: a pooled analysis.

BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.

The PM20D1-NADA pathway protects against Parkinson's disease.

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein (α-Syn) aggregates. However, the molecular mechanisms regulating α-Syn aggregation and neuronal degeneration remain poorly understood. The peptidase M20 domain containing 1 (PM20D1) gene lies within the PARK16 locus genetically linked to PD. Single nucleotide polymorphisms regulating PM20D1 expression are associated with changed risk of PD. Dopamine (DA) metabolism and DA metabolites have been reported to regulate α-Syn pathology. Here we report that PM20D1 catalyzes the conversion of DA to N-arachidonoyl dopamine (NADA), which interacts with α-Syn and inhibits its aggregation. Simultaneously, NADA competes with α-Syn fibrils to regulate TRPV4-mediated calcium influx and downstream phosphatases, thus alleviating α-Syn phosphorylation. The expression of PM20D1 decreases during aging. Overexpression of PM20D1 or the administration of NADA in a mouse model of synucleinopathy alleviated α-Syn pathology, dopaminergic neurodegeneration, and motor impairments. These observations support the protective effect of the PM20D1-NADA pathway against the progression of α-Syn pathology in PD.

METTL3 promotes immature dental pulp stem cells-induced angiogenesis by regulating ETS1 mRNA stability in an m6A-HuR-dependent manner.

Angiogenesis serves as the determinate element of pulp regeneration. Dental pulp stem cell (DPSC) implantation can promote the regeneration of dental pulp tissue. Herein, the role of m6A methyltransferase methyltransferase-like 3 (METTL3) in regulating DPSCs-induced angiogenesis during pulp regeneration therapy was investigated. Cell DPSC viability, HUVEC migration, and angiogenesis ability were analyzed by CCK-8 assay, wound healing, Transwell assay, and tube formation assay. The global and EST1 mRNA m6A levels were detected by m6A dot blot and Me-RIP. The interactions between E26 transformation-specific proto-oncogene 1(ETS1), human antigen R(HuR), and METTL3 were analyzed by RIP assay. The relationship between METTL3 and the m6A site of ETS1 was performed by dual-luciferase reporter assay. ETS1 mRNA stability was examined with actinomycin D. Herein, our results revealed that human immature DPSCs (hIDPSCs) showed stronger ability to induce angiogenesis than human mature DPSCs (hMDPSCs), which might be related to ETS1 upregulation. ETS1 knockdown inhibited DPSCs-induced angiogenesis. Our mechanistic experiments demonstrated that METTL3 increased ETS1 mRNA stability and expression level on DPSCs in an m6A-HuR-dependent manner. ETS1 upregulation abolished sh-METTL3's inhibition on DPSCs-induced angiogenesis. METTL3 upregulation promoted DPSCs-induced angiogenesis by enhancing ETS1 mRNA stability in an m6A-HuR-dependent manner. This study reveals a new mechanism by which m6A methylation regulates angiogenesis in DPSCs, providing new insights for stem cell-based tissue engineering.

Contribution to energy conservation and quality improvement of frozen pork via contact/contactless immersion freezing in NaCl solution.

High energy consumption and quality deterioration are major challenges in the meat freezing process. In this study, the energy consumption and qualities of frozen pork were investigated using three freezing methods: nonpackaged pork air freezing (NAF), contactless immersion freezing (PIF) and contact immersion freezing (NIF) with NaCl solution as a refrigerant. The results indicated that NIF could improve the energy conservation and freezing efficiency in >4 freezing treatment-times by increasing the unfrozen water content, decreasing the frozen heat load, shortening the freezing time and reducing evaporation loss. NIF could also increase the a* value of the pork and improve the water-holding capacity by facilitating the conversion of free water to immobilized-water. The two immersion freezing methods could reduce freezing-thawing loss and protein loss by alleviating muscle tissue freezing damage. These results provide a suitable application of immersion freezing with energy conservation, high efficiency and good quality of frozen-pork.

Easily misdiagnosed X-linked adrenoleukodystrophy.

BACKGROUND: Addison's disease and X-linked adrenoleukodystrophy (X-ALD) (Addison's-only) are two diseases that need to be identified. Addison's disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison's-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison's disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD. METHODS: We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics. RESULTS: Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison's disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394-2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison's-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum. CONCLUSIONS: Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison's disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison's-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.

Advancing hydrogen generation: Kinetic insights and process refinement for sorption-enhanced steam gasification of biomass utilizing waste carbide slag.

Sorption enhanced steam gasification of biomass (SESGB) presents a promising approach for producing high-purity H2 with potential for zero or negative carbon emissions. This study investigated the effects of gasification temperature, CaO to carbon in biomass molar ratio [CaO/C], and steam flow on the SESGB process, employing carbide slag (CS) and its modifications, CSSi2 (mass ratio of CS to SiO2 is 98:2) and CSCG5 (mass ratio of CS to coal gangue (CG) is 95:5), as CaO-based sorbents. The investigation included non-isothermal and isothermal gasification experiments and kinetic analyses using corn cob (CC) in a macro-weight thermogravimetric setup, alongside a fixed-bed pyrolysis-gasification system to assess operational parameter effects on gas product. The results suggested that CO2 capture by CaO reduced the mass loss during the main gasification as the [CaO/C] increased. The appropriate temperature for SESGB process should be selected between 550 and 700 °C at atmospheric pressure. The appropriate amount of sorbent or steam could facilitate the gasification reaction, but excessive addition led to adverse effects. Operational parameters influenced the apparent activation energy (Ea) by affecting various gasification reactions. For each test, Ea at the char gasification stage was significantly higher than that at the rapid pyrolysis stage. The addition of CS notably increased H2 concentration and yield, while sharply reducing CO2 levels. H2 concentration initially rose and then fell with greater steam flow, peaking at 76.11 vol% for a steam flow of 1.0 g/min. H2 yield peaked at 298 mL/g biomass with a steam flow of 1.5 g/min, a gasification temperature of 600 °C and a [CaO/C] of 1.0. Increasing gasification temperature remarkably boosted the H2 and CO2 yields. Optimal conditions for the SESGB using CS as a sorbent, determined via response surface methodology (RSM), include a gasification temperature of 666 °C, a [CaO/C] of 1.99, and a steam flow of 0.5 g/min, under which H2 and CO2 yields were 464 and 48 mL/g biomass, respectively. CSSi2 and CSCG5 demonstrated excellent cyclic H2 production stability, maintaining H2 yields around 440 mL/g biomass and low CO2 yields (∼60 mL/g biomass) across five cycles. The study results offer new insights for the high-value utilization of agroforestry biomass and the reduction and resource utilization of industrial waste.

Phase I clinical trial of intracerebral injection of lentiviral-ABCD1 for the treatment of cerebral adrenoleukodystrophy.

This was a single-arm, multicenter, open-label phase I trial. Lentiviral vectors (LV) carrying the ABCD1 gene (LV-ABCD1) was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy (CCALD), and multi-site injection was performed. The injection dose increased from 200 to 1600 µL (vector titer: 1×109 transduction units per mL (TU/mL)), and the average dose per kilogram body weight ranges from 8 to 63.6 µL/kg. The primary endpoint was safety, dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein. A total of 7 patients participated in this phase I study and were followed for 1 year. No injection-related serious adverse event or death occurred. Common adverse events associated with the injection were irritability (71%, 5/7) and fever (37.2-38.5 â„ƒ, 57%, 4/7). Adverse events were mild and self-limited, or resolved within 3 d of symptomatic treatment. The maximal tolerable dose is 1600 µL. In 5 cases (83.3%, 5/6), no lentivirus associated antibodies were detected. The overall survival at 1-year was 100%. The ABCD1 protein expression was detected in neutrophils, monocytes and lymphocytes. This study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo; even the maximal dose did not increase the risk of adverse events. Furthermore, the direct LV-ABCD1 injection displayed low immunogenicity. In addition, the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is needed. This study has been registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, registration number: ChiCTR1900026649).