Drivers and Pathways for the Recovery of Critical Metals from Waste-Printed Circuit Boards.

The ever-increasing importance of critical metals (CMs) in modern society underscores their resource security and circularity. Waste-printed circuit boards (WPCBs) are particularly attractive reservoirs of CMs due to their gamut CM embedding and ubiquitous presence. However, the recovery of most CMs is out of reach from current metal-centric recycling industries, resulting in a flood loss of refined CMs. Here, 41 types of such spent CMs are identified. To deliver a higher level of CM sustainability, this work provides an insightful overview of paradigm-shifting pathways for CM recovery from WPCBs that have been developed in recent years. As a crucial starting entropy-decreasing step, various strategies of metal enrichment are compared, and the deployment of artificial intelligence (AI) and hyperspectral sensing is highlighted. Then, tailored metal recycling schemes are presented for the platinum group, rare earth, and refractory metals, with emphasis on greener metallurgical methods contributing to transforming CMs into marketable products. In addition, due to the vital nexus of CMs between the environment and energy sectors, the upcycling of CMs into electro-/photo-chemical catalysts for green fuel synthesis is proposed to extend the recycling chain. Finally, the challenges and outlook on this all-round upgrading of WPCB recycling are outlined.

Recent advances in the radical cascade reaction for constructing nitrogen heterocycles using azides as radical acceptors.

Due to the high conversion properties, azide compounds are widely utilized in organic synthesis. For instance, azide compounds readily release nitrogen to form a new N-C bond when they function as radical acceptors for the active intermediates in the reaction. Over the past decade, strategies employing azides as radical acceptors to construct nitrogen heterocycles have been extensively developed. This approach has emerged as a crucial method for synthesizing nitrogen heterocycles. Therefore, this paper provides a review of the research advancements in tandem cyclization reactions using azides as radical acceptors, summarizing the process of reaction design, exploration, reasoning of the mechanism, and prospects for further research of these reactions.

Social risk to infant: The role of kin for maternal visual monitoring in Tibetan macaques.

Maternal monitoring of conspecifics is a crucial anti-predator strategy that also protects infants against risks within the social group. This study examines how maternal characteristics, infant characteristics, mother-infant distance, and the social environment affect maternal monitoring behaviors in free-ranging Tibetan macaques (Macaca thibetana). We observed 12 females with infants and analyzed their visual monitoring patterns. Our findings indicate that maternal rank significantly influences the time allocated to maternal visual monitoring, higher-ranking mothers spending less time than lower-ranking mothers. Maternal experience also played a role in monitoring strategies. Differences in monitoring strategies were observed based on maternal experience: first-time mothers (primiparity) engaged in longer but less frequent monitoring sessions compared to experienced mothers (multiparity). The time and frequency of maternal monitoring decreased as infants aged, and mothers with male infants showed higher levels of monitoring than those with female infants. The distance between mother and infant also affected visual monitoring behavior, with mothers increasing their monitoring levels when infants were nearby (1-5 m), rather than within reach (0-1 m) or beyond nearby (>5 m). Additionally, the presence of kin and non-kin influenced monitoring: as the number of nearby kin increased, monitoring levels decreased, while the presence of more non-kin males led to an increase in monitoring time, and higher-ranking non-kin neighbors increased the frequency of monitoring. These results suggest that Tibetan macaque mothers can adapt their visual monitoring to the social risks faced by their infants, adjusting their strategies to their status and the needs of their offspring.

Large-scale statistical analysis of Mycobacterium tuberculosis genome sequences identifies compensatory mutations associated with multi-drug resistance.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, has a significant impact on global health worldwide. The development of multi-drug resistant strains that are resistant to the first-line drugs isoniazid and rifampicin threatens public health security. Rifampicin and isoniazid resistance are largely underpinned by mutations in rpoB and katG respectively and are associated with fitness costs. Compensatory mutations are considered to alleviate these fitness costs and have been observed in rpoC/rpoA (rifampicin) and oxyR'-ahpC (isoniazid). We developed a framework (CompMut-TB) to detect compensatory mutations from whole genome sequences from a large dataset comprised of 18,396 M. tuberculosis samples. We performed association analysis (Fisher's exact tests) to identify pairs of mutations that are associated with drug-resistance, followed by mediation analysis to identify complementary or full mediators of drug-resistance. The analyses revealed several potential mutations in rpoC (N = 47), rpoA (N = 4), and oxyR'-ahpC (N = 7) that were considered either 'highly likely' or 'likely' to confer compensatory effects on drug-resistance, including mutations that have previously been reported and validated. Overall, we have developed the CompMut-TB framework which can assist with identifying compensatory mutations which is important for more precise genome-based profiling of drug-resistant TB strains and to further understanding of the evolutionary mechanisms that underpin drug-resistance.

Temporal niche partitioning among sympatric wild and domestic ungulates between warm and cold seasons.

The coexistence of sympatric species with similar ecological niches has been a central issue in ecology. Clarifying the daily activity patterns of sympatric wild ungulates can help understand their temporal niche differentiation and the mechanisms of coexistence, providing information for their conservation. The Baotianman National Nature Reserve in northern China is rich in wild ungulates, but little is known about the daily activity patterns of wild ungulates in the area, making it difficult to develop effective conservation strategies. We studied five representative wild ungulates (i.e. forest musk deer, Chinese goral, Reeve's muntjac, Siberian roe deer, and wild boar) of the region using camera-trapping data, focusing on the seasonal daily activity patterns and effects of seasonal grazing of domestic sheep, to reveal their coexistence based on temporal ecological niche differentiation. Comparative analyses of the seasonal daily activity showed that forest musk deer exhibited a single-peak activity in the warm season. Other ungulates exhibited multipeak activity. All five ungulates differed significantly in daily activity patterns. Notably, wild boar and Reeve's muntjac showed high overlap coefficients between the cold and warm seasons. In both cold and warm seasons, the five wild ungulates and domestic sheep displayed low overlap in their daily activity rhythms potentially indicating temporal ecological niche differentiation. The results suggest that temporal isolation might be a strategy for wild ungulates to avoid domestic sheep and reduce interspecific competition, and that temporal ecological niche differentiation potentially promoted the coexistence among the studied sympatric ungulates. This understanding may provide new insights for the development of targeted conservation strategies.

A cross-linked macropore hydrogel based on M1 macrophage lysate and alginate regulates tumor-associated macrophages for the treatment of melanoma.

Pro-inflammatory M1 macrophages possess the ability to change the immunosuppressive tumor microenvironment by releasing various inflammatory factors simultaneously, which can effectively inhibit tumor progression and relapse. Promoting macrophage polarization towards M1 may be an effective way to treat Melanoma. However, the risk of cytokine storm caused by the proliferation and excessive activation of M1 macrophages greatly limits it as a biosafety therapeutic strategy in anti-tumor immunotherapy. Therefore, how to engineer natural M1 macrophage to a biocompatible biomaterial that maintains the duration time of tumor suppressive property duration time still remains a huge challenge. To achieve this goal, we developed an injectable macroporous hydrogel (M1LMHA) using natural M1 macrophage lysates and alginate as raw materials. M1LMHA had excellent biocompatibility, adjustable degradation rate and could sustainably release varieties of natural inflammatory factors, such as tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), etc. M1LMHA could repolarize anti-inflammatory M2 macrophages to M1 macrophages by the synergistic effect of released tiny inflammatory factors via the NF-κB pathway. This study supported that M1LMHA might be an effective and safe tool to activate tumor-associated immune cells, improving the efficiency of anti-tumor immunotherapy.

Seasonal human coronavirus NL63 epidemics in children in Guilin, China, reveal the emergence of a new subgenotype of HCoV-NL63.

Introduction: Seasonal human coronavirus NL63 (HCoV-NL63) is a frequently encountered virus linked to mild upper respiratory infections. However, its potential to cause more severe or widespread disease remains an area of concern. This study aimed to investigate a rare localized epidemic of HCoV-NL63-induced respiratory infections among pediatric patients in Guilin, China, and to understand the viral subtype distribution and genetic characteristics. Methods: In this study, 83 pediatric patients hospitalized with acute respiratory infections and positive for HCoV-NL63 were enrolled. Molecular analysis was conducted to identify the viral subgenotypes and to assess genetic variations in the receptor-binding domain of the spiking protein. Results: Among the 83 HCoV-NL63-positive children, three subgenotypes were identified: C4, C3, and B. Notably, 21 cases exhibited a previously unreported subtype, C4. Analysis of the C4 subtype revealed a unique amino acid mutation (I507L) in the receptor-binding domain of the spiking protein, which was also observed in the previously reported C3 genotype. This mutation may suggest potential increases in viral transmissibility and pathogenicity. Discussion: The findings of this study highlight the rapid mutation dynamics of HCoV-NL63 and its potential for increased virulence and epidemic transmission. The presence of a unique mutation in the C4 subtype, shared with the C3 genotype, raises concerns about the virus's evolving nature and its potential public health implications. This research contributes valuable insights into the understanding of HCoV-NL63's epidemiology and pathogenesis, which is crucial for effective disease prevention and control strategies. Future studies are needed to further investigate the biological significance of the observed mutation and its potential impact on the virus's transmissibility and pathogenicity.

The role of preoperative FPR and FAR in prognostic evaluation of stages II and III radical colorectal cancer: A single-center retrospective study.

The inflammatory and nutritional states of body are 2 important causes associated with the initiation and progression of colorectal cancer (CRC). The aim of this study is to investigate the prognostic evaluation value of preoperative fibrinogen-to-prealbumin ratio (FPR) and preoperative fibrinogen-to-albumin ratio (FAR) in CRC. The clinical data of 350 stages II and III patients with CRC who received radical resection were retrospectively analyzed. All patients were followed up for 5 years to observe the overall survival and disease-free survival of 5 years and analyze the relationship between preoperative FPR and FAR and prognosis of all enrolled patients. In addition, we analyzed the diagnostic and application value of combined biomarkers. This study showed high-level preoperative FPR and FAR were significantly associated with poor overall survival and disease-free survival of stages II and III patients with CRC. The elevated preoperative FPR and FAR level was significantly related to age, tumor differentiation level, TNM stage, vascular infiltration, carcinoembryonic antigen, carbohydrate antigen199, etc. The combination of FPR, FAR, neutrophil-to-lymphocyte ratio, and carbohydrate antigen199 had the maximum area under curve (AUC = 0.856, 95% CI: 0.814-0.897, Sen = 78.20%, Spe = 82.49%, P < .05) under the receiver-operating characteristics curve. The preoperative FPR and FAR have important prognostic value and they can be used as independent prognostic marker for patients with stages II and III CRC undergoing radical resection. Moreover, the combination of biomarkers could further enhance the diagnostic and prognostic efficacy of CRC.

Abdominopelvic desmoplastic small round cell tumor with metastasis: A case report and literature review.

RATIONALE: Desmoplastic small round cell tumor (DSRCT) is a rare and rapidly metastasizing soft tissue sarcoma, distinguished by its unique cell morphology and pleomorphic differentiation. PATIENT CONCERNS: This report describes the case of an 18-year-old male diagnosed with abdominopelvic DSRCT exhibiting metastases to the peritoneum, liver, pleura, bone, and muscle. The patient primarily presented with symptoms of incomplete intestinal obstruction and an abdominal mass. DIAGNOSES: Colonoscopy revealed lumen stenosis caused by external compression mass. Contrast-enhanced computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed multiple lesions in the abdominopelvic cavity. A needle biopsy of an abdominal wall lesion established it as a malignant tumor, origin unknown. Immunohistochemical staining post-surgery showed positive results for Cytokeratin (CK), CK7, Desmin, Vimentin, Caudal type homeobox 2 (CDX2), and Ki-67. Fluorescence in situ hybridization analysis revealed an Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1 (EWSR1) rearrangement, and next-generation sequencing identified an EWSR1-Wilms tumor protein 1 (WT1) gene fusion. INTERVENTIONS: The patient underwent laparoscopic exploratory surgery, which encompassed biopsy, ascites drainage, adhesion lysis, reinforcement of weakened sections of the small intestinal walls, and repositioning of twisted intestines. Postoperatively, the treatment protocol included fasting, rehydration, gastrointestinal decompression, and parenteral nutrition. However, the patient did not received chemotherapy. OUTCOMES: The patient declined further treatment and deceased in early November. LESSONS: This case highlights the nonspecific nature of DSRCT symptoms. In clinical practice, it is crucial to meticulously evaluate unexplained intestinal obstruction in young patients, considering DSRCT as a differential diagnosis to avoid delays in diagnosis.

Precious Metal Free Hydrogen Evolution Catalyst Design and Application.

The quest to identify precious metal free hydrogen evolution reaction catalysts has received unprecedented attention in the past decade. In this Review, we focus our attention to recent developments in precious metal free hydrogen evolution reactions in acidic and alkaline electrolyte owing to their relevance to commercial and near-commercial low-temperature electrolyzers. We provide a detailed review and critical analysis of catalyst activity and stability performance measurements and metrics commonly deployed in the literature, as well as review best practices for experimental measurements (both in half-cell three-electrode configurations and in two-electrode device testing). In particular, we discuss the transition from laboratory-scale hydrogen evolution reaction (HER) catalyst measurements to those in single cells, which is a critical aspect crucial for scaling up from laboratory to industrial settings but often overlooked. Furthermore, we review the numerous catalyst design strategies deployed across the precious metal free HER literature. Subsequently, we showcase some of the most commonly investigated families of precious metal free HER catalysts; molybdenum disulfide-based, transition metal phosphides, and transition metal carbides for acidic electrolyte; nickel molybdenum and transition metal phosphides for alkaline. This includes a comprehensive analysis comparing the HER activity between several families of materials highlighting the recent stagnation with regards to enhancing the intrinsic activity of precious metal free hydrogen evolution reaction catalysts. Finally, we summarize future directions and provide recommendations for the field in this area of electrocatalysis.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with increasing morbidity and mortality due to changes of social environment. AIM: To evaluate the significance of serum carbohydrate antigen 19-9 (CA19-9) and tumor size changes pre- and post-neoadjuvant therapy (NAT). METHODS: This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital. This study specifically assessed CA19-9 levels and tumor size before and after NAT. RESULTS: A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study. The average age was 65.4 ± 10.6 years and 72 (46.2%) patients were female. Before survival analysis, we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio (CR). The patients were divided into three groups: CR < 0.5, CR > 0.5 and < 1 and CR > 1. With regard to tumor size measured by both computed tomography and magnetic resonance imaging, we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio (TR). The patients were then divided into three groups: TR < 0.5, TR > 0.5 and < 1 and TR > 1. Based on these groups divided according to CR and TR, we performed both overall survival (OS) and disease-free survival (DFS) analyses. Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR (P < 0.05). CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response. Moreover, CR (hazard ratio: 1.721, 95%CI: 1.373-3.762; P = 0.006), and TR (hazard ratio: 1.435, 95%CI: 1.275-4.363; P = 0.014) were identified as independent factors associated with OS. CONCLUSION: This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.

Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable; however, designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated drug product for targeting CD33+ tumors called dimerizaing agent-regulated immunoreceptor complex (DARIC33). T cell products demonstrated target-specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1 nM rapamycin. Rapamycin withdrawal paused DARIC33-stimulated T cell effector functions, which were restored following reexposure to rapamycin, demonstrating reversible effector function control. While rapamycin-regulated DARIC33 T cells were highly sensitive to target antigen, CD34+ stem cell colony-forming capacity was not impacted. We benchmarked DARIC33 potency relative to CD19 CAR T cells to estimate a T cell dose for clinical testing. In addition, we integrated in vitro and preclinical in vivo drug concentration thresholds for off-on state transitions, as well as murine and human rapamycin pharmacokinetics, to estimate a clinically applicable rapamycin dosing schedule. A phase I DARIC33 trial has been initiated (PLAT-08, NCT05105152), with initial evidence of rapamycin-regulated T cell activation and antitumor impact. Our findings provide evidence that the DARIC platform exhibits sensitive regulation and potency needed for clinical application to other important immunotherapy targets.

Effect of Day Length on Growth and Gonadal Development in Meishan Male Pigs.

Day length is a critical environmental factor for regulating animal growth and development. This study aimed to investigate the effects of different day lengths on the developmental changes of growth parameters, testicular sizes, testosterone secretion in Meishan male pigs, and steroidogenesis proteins and melatonin receptors. Fourteen Meishan male pigs (10 weeks (wks) of age) with the same parity, paired in litter and body weight (BW), were evenly allocated into a short-day-length group (SDL, 10 light/14 dark) and long-day-length group (LDL, 14 light/10 dark). After 12 wks of the experiment, the LDL-treated boars had more lying time and less exploring time. The LDL treatment led to significant increases in body height, chest circumference, testicular length, testicular weight, crude protein digestibility, and fecal testosterone at the 10th and 12th wks of the experiment, and cortisol at the 10th wk, compared to the SDL treatment, with no differences in the final BW, testicular width, and epididymis weight. Furthermore, the LDL treatment significantly increased the protein levels of melatonin receptor 1b (MT2), aromatase (CYP19), and steroidogenic factor 1 (SF1) in the testis, with no differences in the protein levels of melatonin receptor 1a (MT1), steroidogenic acute regulatory (StAR), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), and cholesterol side-chain cleavage enzyme (P450scc). The present study suggests that day length has an effect on the growth and gonadal development in male pigs maybe via MT2 and influences steroid synthesis and secretion in the testis. Therefore, proper day length should be considered in male pig breeding.

Ultrathin LayCoOx Nanosheets with High Porosity Featuring Boosted Catalytic Oxidation of Benzene: Mechanism Elucidation via an Experiment-Theory Combined Paradigm.

Designing transition-metal oxides for catalytically removing the highly toxic benzene holds significance in addressing indoor/outdoor environmental pollution issues. Herein, we successfully synthesized ultrathin LayCoOx nanosheets (thickness of ∼1.8 nm) with high porosity, using a straightforward coprecipitation method. Comprehensive characterization techniques were employed to analyze the synthesized LayCoOx catalysts, revealing their low crystallinity, high surface area, and abundant porosity. Catalytic benzene oxidation tests demonstrated that the La0.029CoOx-300 nanosheet exhibited the most optimal performance. This catalyst enabled complete benzene degradation at a relatively low temperature of 220 °C, even under a high space velocity (SV) of 20,000 h-1, and displayed remarkable durability throughout various catalytic assessments, including SV variations, exposure to water vapor, recycling, and long time-on-stream tests. Characterization analyses confirmed the enhanced interactions between Co and doped La, the presence of abundant adsorbed oxygen, and the extensive exposure of Co3+ species in La0.029CoOx-300 nanosheets. Theoretical calculations further revealed that La doping was beneficial for the formation of oxygen vacancies and the adsorption of more hydroxyl groups. These features strongly promoted the adsorption and activation of oxygen, thereby accelerating the benzene oxidation processes. This work underscores the advantages of doping rare-earth elements into transition-metal oxides as a cost-effective yet efficient strategy for purifying industrial exhausts.

Electrothermal Transformations within Graphene-Based Aerogels through High-Temperature Flash Joule Heating.

Flash Joule heating of highly porous graphene oxide (GO) aerogel monoliths to ultrahigh temperatures is exploited as a low carbon footprint technology to engineer functional aerogel materials. Aerogel Joule heating to up to 3000 K is demonstrated for the first time, with fast heating kinetics (∼300 K·min-1), enabling rapid and energy-efficient flash heating treatments. The wide applicability of ultrahigh-temperature flash Joule heating is exploited in a range of material fabrication challenges. Ultrahigh-temperature Joule heating is used for rapid graphitic annealing of hydrothermal GO aerogels at fast time scales (30-300 s) and substantially reduced energy costs. Flash aerogel heating to ultrahigh temperatures is exploited for the in situ synthesis of ultrafine nanoparticles (Pt, Cu, and MoO2) embedded within the hybrid aerogel structure. The shockwave heating approach enables high through-volume uniformity of the formed nanoparticles, while nanoparticle size can be readily tuned through controlling Joule-heating durations between 1 and 10 s. As such, the ultrahigh-temperature Joule-heating approach introduced here has important implications for a wide variety of applications for graphene-based aerogels, including 3D thermoelectric materials, extreme temperature sensors, and aerogel catalysts in flow (electro)chemistry.

Fecal microbial composition associated with testosterone in the development of Meishan male pigs.

Introduction: The gut microbiota closely relates to host health, whereas the relationship between gut microbiota and testosterone during the development of Meishan male pigs remains unclear. This study investigated the fecal microbiota composition and testosterone level during development in Meishan male pigs. Methods: Fresh fecal samples of 20 healthy Meishan male pigs were individually collected at 10 and 22 weeks (wk) of age for testosterone content detection and bacteria pyrosequencing analysis. Anaerobic culture experiment of fecal bacteria in vitro was performed for bacteria pyrosequencing analysis. Results: The fecal testosterone content increased significantly from 10 weeks (wk) to 22 wk of age (P < 0.05). Meanwhile, the boars at 22 wk had a lower abundance of phylum Bacteroidetes and Proteobacteria, and genus Alloprevotella, Prevotella_1, Prevotellaceae_NK3B31_group, and Streptococcus in the fecal microbiota composition (P < 0.05). but higher proportions of the phylum Actinobacteria, Firmicutes, Kiritimatiellaeota, and Tenericutes, and genus Clostridium_sensu_stricto_1, Muribaculaceae and Terrisporobacter than that at 10 wk (P < 0.05), and the Firmicutes to Bacteroidetes ratio was higher at 22 wk than 10 wk (P < 0.05). Moreover, the fecal testosterone level significantly correlated with the relative abundance of the phylum Actinobacteria, Firmicutes, and Tencuteseri, and genus Alloprevotella, Clostridium_sensu_stricto_1, Muribaculaceae, Prevotella_1 and Streptococcus. Furthermore, the in vitro experiments indicated that the abundance of the phylum Proteobacteria and genus Escherichia-Shigella reduced with the increase of supplemental testosterone level. In contrast, the proportion of Firmicutes phylum increased with additional testosterone levels. Discussion: Testosterone could modulate the microflora structure. Meanwhile, the bacteria could degrade the testosterone in a dose testosterone-dependent manner. These results provide us with new insights into the relationship between the gut microbiome and testosterone and the contributions of the gut microbiome in physiological regulation in response to gonad development.

Characteristics and time points to inhibit ferroptosis in human osteoarthritis.

Ferroptosis is a form of cell death that is triggered by iron-dependent lipid peroxidation and is closely associated with osteoarthritis. The primary interventions for inhibiting ferroptosis in osteoarthritis are anti-lipid peroxidation and iron chelation. The objective of our study is to investigate the characteristics of ferroptosis in osteoarthritis and identify the optimal time points for inhibiting ferroptosis to alleviate disease progression. Ferroptosis-related alterations and markers of OA were analyzed in paired intact and damaged cartilages from OA patients by immunofluorescence, qRT-PCR, mitochondrial membrane potential and immunohistochemistry. We also compared Ferroptosis-related alterations in cartilage of mild, moderate, and severe OA (according to the modified Mankin score). In addition, we compared the effect of Fer-1 on ferroptosis and the protection of chondrocytes by detecting markers of both ferroptosis and OA by immunofluorescence, CCK8 and qRT-PCR. Ferroptosis-related alterations (GPX4 downregulation, ACSL4 upregulation, MDA, LPO accumulation, Mitochondrial membrane potential decreased) in the damaged area cartilage were more severe than those in the intact area and increased with the progression of OA. Compared with mild OA group, the activity of chondrocytes treated with Fer-1 (a ferroptosis inhibitor) was increased, mitochondrial function was improved, and ferroptosis was reduced (GPX4 upregulation, SLC7A11 upregulation, ACSL4 downregulation,), and promoted the expression of COL2A1 and inhibited the expression of MMP13. However, these changes were not observed in moderate and severe OA chondrocytes. Ferroptosis occurs in a region-specific manner and is exacerbated with the progression of human OA cartilage degeneration. Inhibition of ferroptosis might had a therapeutic effect on chondrocytes with mild OA but had no significant therapeutic effect on chondrocytes with moderate to severe OA.

[Unilateral interlaminar approach 270° circular spinal canal decompression under the iLESSYS Delta for the treatment of lumbar spinal stenosis in the elderly].

OBJECTIVE: To investigate the clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the Interlaminar Endoscopic Surgical System(iLESSYS) Delta for the treatment of lumbar spinal stenosis (LSS) in the elderly. METHODS: Total of 29 patients with LSS treated with the iLESSYS Delta from December 2018 to January 2021 were retrospectively analyzed, including 12 males and 17 females with an average age of (71.52±10.82) years old ranging from 63 to 83 years old. All patients had definite intermittent claudication, mainly neurogenic symptoms of both lower limbs. All patients had single-level spinal stenosis, including L3,4 5 cases, L4,5 21 cases, and L5S1 3 cases. Visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified Macnab assessment criteria were used to evaluate pain, low back pain dysfunction index and clinical efficacy, respectively. RESULTS: All 29 cases were successfully completed. The operation time was (73.45±5.89) min, the intraoperative blood loss was (9.93±0.83) ml, the hospital stay was (4.03±0.41) days, and the follow-up was more than 12 months. The VAS scores of low back pain before surgery and 1 day, 1 month, 3 months, 1 year after surgery were 2.31±0.88, 1.45±0.62, 1.21±0.61, 1.10±0.55, 1.03±0.49;VAS of leg pain were 6.48±0.49 0.56, 1.97±0.61, 1.31±0.59, 1.17±0.59, 1.10±0.55;ODI scores were 38.41±2.74, 18.14±1.17, 5.17±0.53, 5.07±0.45, 4.90±0.48;low back and leg pain VAS score and ODI score have statistically significant differences between preoperative and postoperative follow-up time points (P<0.05). The MacNab efficacy evaluation at 1-year follow-up:excellent in 22 cases, good in 5 cases and fair in 2 cases. CONCLUSION: The clinical effect of unilateral interlaminar approach 270° circular spinal canal decompression under the iLESSYS Delta for the treatment of lumbar spinal stenosis in the elderly is satisfactory, with the advantages of less trauma and less bleeding, large microscopic operation space, sufficient decompression, and ideal post-operative recovery, and at the same time, it can minimize the damage to the stable structure of the lumbar spine, which is an ideal surgical method for the treatment of elderly lumbar spinal stenosis.

[Development progress of stationary phase for supercritical fluid chromatography and related application in natural products].

Supercritical fluid chromatography (SFC) is an environment-friendly and efficient column chromatography technology that was developed to expand the application range of high performance liquid chromatography (HPLC) using a supercritical fluid as the mobile phase. A supercritical fluid has a temperature and pressure that are above the critical values as well as relatively dynamic characteristics that are between those of a gas and liquid. Supercritical fluids combine the advantages of high solubility and diffusion, as their diffusion and viscosity coefficients are equivalent to those of a gas, while maintaining a density that is comparable with that of a liquid. Owing to the remarkable compressibility of supercritical fluids, analyte retention in SFC is significantly influenced by the density of the mobile phase. Thus, the column temperature and back pressure are crucial variables that regulate analyte retention in SFC. Increasing the back pressure can increase the density and solubility of the mobile phase, leading to reductions in retention time. The column temperature can affect selectivity and retention, and the degree to which different analytes are affected by this property varies. On the one hand, increasing the temperature reduces the density of the mobile phase, thereby extending the retention time of the analytes; on the other hand, it can also increase the energy of molecules, leading to a shorter retention time of the analyte on the stationary phase. CO2, the most widely employed supercritical fluid to date, presents moderate critical conditions and, more importantly, is miscible with a variety of polar organic solvents, including small quantities of water. In comparison with the mobile phases used in normal-phase liquid chromatography (NPLC) and reversed-phase liquid chromatography (RPLC), the mobile phase for SFC has a polarity that can be extended over a wide range on account of its extensive miscibility. The compatibility of the mobile phase determines the diversity of the stationary phase. Nearly all stationary phases for HPLC, including the nonpolar stationary phases commonly used for RPLC and the polar stationary phases commonly used for NPLC, can be applied to SFC. Because all stationary phases can use the same mobile-phase composition, chromatographic columns with completely different polarities can be employed in SFC. The selectivity of SFC has been effectively expanded, and the technique can be used for the separation of diverse analytes ranging from lipid compounds to polar compounds such as flavonoids, saponins, and peptides. The choice of stationary phase has a great impact on the separation effect of analytes in SFC. As new stationary phases for HPLC are constantly investigated, specialized stationary phases for SFC have also been continuously developed. Researchers have discovered that polar stationary phases containing nitrogen heterocycles such as 2-EP and PIC are highly suitable for SFC because they can effectively manage the peak shape of alkaline compounds and provide good selectivity in separating acidic and neutral compounds.The development of various stationary phases has promoted the applications of SFC in numerous fields such as pharmaceuticals, food production, environmental protection, and natural products. In particular, natural products have specific active skeletons, multiple active groups, and excellent biological activity; hence, these materials can provide many new opportunities for the discovery of novel drugs. According to reports, compounds related to natural products account for 80% of all commercial drugs. However, natural products are among the most challenging compounds to separate because of their complex composition and low concentration of active ingredients. Thus, superior chromatographic methods are required to enable the qualitative and quantitative analysis of natural products. Thanks to technological improvements and a good theoretical framework, the benefits of SFC are gradually becoming more apparent, and its use in separating natural products is expanding. Indeed, in the past 50 years, SFC has developed into a widely used and efficient separation technology. This article provides a brief overview of the characteristics, advantages, and development process of SFC; reviews the available SFC stationary phases and their applications in natural products over the last decade; and discusses prospects on the future development of SFC.

Macrophages depletion alleviates lung injury by modulating AKT3/GXP4 following ventilator associated pneumonia.

Background: AKT3 appears to play a role in lung cancer. However, its role in ventilator-associated pneumonia is still unclear. Therefore, this study aimed to investigate the role of AKT3 in macrophages during ventilator-associated pneumonia. Methods: The mRNA level of AKT3, Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The data is analyzed using the Xiantao academic analysis tool. Additionally, the roles of AKT3 in ventilator-associated pneumonia (VAP) were investigated through in vivo experiments. Results: AKT3 was differentially expressed in various normal and tumor tissues. Functional enrichment analysis indicated the immunomodulatory function and inflammatory response of AKT3 in lung cancer. Depletion of macrophages protected against lung epithelial cells and significantly decreased MMP9, MMP19, FTH, and FTL expression levels and increased GPX4 expression levels, while partially reversing the changes in macrophage. Mechanistically, macrophage depletion attenuates ferroptosis of lung epithelial cells by modulating AKT3 following VAP. Conclusion: Collectively, this study suggests the need for further validation of the immunoregulatory function of AKT3 in lung cancer. Additionally, macrophage depletion mitigates lung injury by modulating the AKT3/GPX4 pathway in the context of VAP.