Comparative Analysis of Short-Term and Long-Term Clinical Efficacy of Mesenchymal Stem Cells from Different Sources in Knee Osteoarthritis: A Network Meta-Analysis.

Background: Joint articular injection of mesenchymal stem cells (MSCs) has emerged as a novel treatment approach for osteoarthritis (OA). However, the effectiveness of MSCs derived from different sources in treating OA patients remains unclear. Therefore, this study aimed to explore the differences between the effectiveness and safety of different sources of MSCs. Materials and Methods: For inclusion consideration, we searched trial registries and published databases, including PubMed, Cochrane Library, Embase, and Web of Science databases. Revman (V5.3), STATA (V16.0), and R (V4.0) were utilized for conducting data analysis, while the Cochrane Risk of Bias Tool was employed for assessing the quality of the studies. We derived outcome measures at 6 and 12 months based on the duration of study follow-up, including visual analog scale (VAS) score, WOMAC score, WOMAC pain, WOMAC Functional Limitation, and WOMAC stiffness. The evaluation time for short-term effectiveness is set at 6 months, while 12 months is utilized as the longest follow-up time for most studies to assess long-term effectiveness. Results: The evaluation of literature quality showed that the included studies had excellent methodological quality. A meta-analysis revealed that different sources of MSCs improved knee function and pain more effectively among patients suffering from knee OA (KOA) than controls. The results of the network meta-analysis showed the following: short-term functional improvement (the indexes were evaluated after 6 months of follow-up) (WOMAC total score: bone marrow-derived MSC (BMMSC) vs. adipose-derived MSC (ADMSC) (mean difference (MD) = -20.12, 95% confidence interval (CI) -125.24 to 42.88), umbilical cord-derived MSC (UCMSC) (MD = -7.81, 95% CI -158.13 to 74.99); WOMAC stiffness: BMMSC vs. ADMSC (MD = -0.51, 95% CI -7.27 to 4.29), UCMSC (MD = -0.75, 95% CI -9.74 to 6.63); WOMAC functional limitation: BMMSC vs. ADMSC (MD = -12.22, 95% CI -35.05 to 18.86), UCMSC (MD = -9.31, 95% CI -44.26 to 35.27)). Long-term functional improvement (the indexes were evaluated after 12 months of follow-up) (WOMAC total: BMMSC vs. ADMSC (MD = -176.77, 95% CI -757.1 to 378.25), UCMSC (MD = -181.55, 95% CI -937.83 to 541.13); WOMAC stiffness: BMMSC vs. ADMSC (MD = -0.5, 95% CI -26.05 to 18.61), UCMSC (MD = -1.03, 95% CI -30.44 to 21.69); WOMAC functional limitation: BMMSC vs. ADMSC (MD = -5.18, 95% CI -316.72 to 177.1), UCMSC (MD = -8.33, 95% CI -358.78 to 218.76)). Short-term pain relief (the indexes were evaluated after 6 months of follow-up) (VAS score: UCMSC vs. BMMSC (MD = -10.92, 95% CI -31.79 to 12.03), ADMSC (MD = -14.02, 95% CI -36.01 to 9.81), PLMSC (MD = -17.09, 95% CI -46.31 to 13.17); WOMAC pain relief: BMMSC vs. ADMSC (MD = -11.42, 95% CI -39.52 to 11.77), UCMSC (MD = -6.73, 95% CI -47.36 to 29.15)). Long-term pain relief (the indexes were evaluated after 12 months of follow-up) (VAS score: BMMSC vs. UCMSC (MD = -4.33, 95% CI -36.81 to 27.08), ADMSC (MD = -11.43, 95% CI -37.5 to 13.42); WOMAC pain relief: UCMSC vs. ADMSC (MD = 0.23, 95% CI -37.87 to 38.11), BMMSC (MD = 5.89, 95% CI -25.39 to 51.41)). According to the GRADE scoring system, WOMAC, VAS, and AE scores were of low quality. Conclusion: Meta-analysis suggests MSCs can effectively treat KOA by improving pain and knee function compared to control groups. In terms of functional improvement in KOA patients, both short-term (6-month follow-up) and long-term (12-month follow-up) results indicated that while the differences between most treatments were not statistically significant, bone marrow-derived MSCs may have some advantages over other sources of MSCs. Additionally, BM-MSCs and UC-MSCs may offer certain benefits over ADMSCs in terms of pain relief for KOA patients, although the variances between most studies were not statistically significant. Therefore, this study suggests that BM-MSCs may present clinical advantages over other sources of MSCs.

Sustainable thermal regulation improves stability and efficiency in all-perovskite tandem solar cells.

Mixed Sn-Pb perovskites have emerged as promising photovoltaic materials for both single- and multi-junction solar cells. However, achieving their scale-up and practical application requires further enhancement in stability. We identify that their poor thermal conductivity results in insufficient thermal transfer, leading to heat accumulation within the absorber layer that accelerates thermal degradation. A thermal regulation strategy by incorporating carboranes into perovskites is developed; these are electron-delocalized carbon-boron molecules known for their efficient heat transfer capability. We specifically select ortho-carborane due to its low thermal hysteresis. We observe its existence through the perovskite layer showing a decreasing trend from the buried interface to the top surface, effectively transferring heat and lowering the surface temperature by around 5 °C under illumination. o-CB also facilitates hole extraction at the perovskite/PEDOT:PSS interface and reduces charge recombination. These enable mixed Sn-Pb cells to exhibit improved thermal stability, retaining 80% of their initial efficiencies after aging at 85 °C for 1080 hours. When integrated into monolithic all-perovskite tandems, we achieve efficiencies of over 27%. A tandem cell maintains 87% of its initial PCE after 704 h of continuous operation under illumination.

Neuroimaging with Rotterdam Scoring System and long-term outcomes in severe traumatic brain injury patients.

PURPOSE: The Rotterdam Scoring System (RSS) attempts to prognosticate early mortality and early functional outcome in patients with traumatic brain injury (TBI) based on non-contrast head computed tomography (CT) imaging findings. The purpose of this study was to identify the relationship between RSS scores and long-term outcomes in patients with severe TBI. METHODS: Consecutively treated patients with severe TBI enrolled between 2008 and 2011, in the prospective, observational, Brain Trauma Research Center database were included. The Glasgow Outcome Scale (GOS) was used to measure long-term functional outcomes at three, six, 12, and 24 months. GOS scores were categorized into favorable (GOS = 4-5) and unfavorable (GOS = 1-3) outcomes. RSS scores were calculated at the time of image acquisition. RESULTS: Of the 89 patients included, 74 (83.4%) were male, 81 (91.0%) were Caucasian, and the mean age of the cohort was 41.9 ± 18.5 years old. Patients with an RSS score of 3 and lower were more likely to have a favorable outcome with increased survival rates than patients with RSS scores greater than 3. CONCLUSIONS: The RSS score determined on the head CT scan acquired at admission in a cohort of patients with severe TBI correlated with long-term survival and functional outcomes up to two years following injury.

The Construction of Anion-Induced Solvation Structures in Low-concentration Electrolyte for Stable Zinc Anodes.

Aqueous zinc-ion batteries (ZIBs) are promising large-scale energy storage devices because of their low cost and high safety. However, owing to the high activity of H2O molecules in electrolytes, hydrogen evolution reaction and side reactions usually take place on Zn anodes. Herein, additive-free PCA-Zn electrolyte with capacity of suppressing the activity of free and solvated H2O molecules was designed by selecting the cationophilic and solventophilic anions. In such electrolyte, contact ion-pairs and solvent-shared ion-pairs were achieved even at low concentration, where PCA- anions coordinate with Zn2+ and bond with solvated H2O molecules. Simultaneously, PCA- anions also induce the construction of H-bonds between free H2O molecules and them. Therefore, the activity of free and solvated H2O molecules is effectively restrained. Furthermore, since PCA- anions possess a strong affinity with metal Zn, they can also adsorb on Zn anode surface to protect Zn anode from the direct contact of H2O molecules, inhibiting the occurrence of water-triggered side reactions. As a result, plating/stripping behavior of Zn anodes is highly reversible and the coulombic efficiency can reach to 99.43 % in PCA-Zn electrolyte. To illustrate the feasibility of PCA-Zn electrolyte, the Zn||PANI full batteries were assembled based on PCA-Zn electrolyte and exhibited enhanced cycling performance.

Oral administration of ellagic acid mitigates perioperative neurocognitive disorders, hippocampal oxidative stress, and neuroinflammation in aged mice by restoring IGF-1 signaling.

This study investigates the potential of ellagic acid (EA), a phytochemical with antioxidant and anti-inflammatory properties, in managing perioperative neurocognitive disorders (PND). PND, which represents a spectrum of cognitive impairments often faced by elderly patients, is principally linked to surgical and anesthesia procedures, and heavily impacted by oxidative stress in the hippocampus and microglia-induced neuroinflammation. Employing an aged mice model subjected to abdominal surgery, we delve into EA's ability to counteract postoperative oxidative stress and cerebral inflammation by engaging the Insulin-like growth factor-1 (IGF-1) pathway. Our findings revealed that administering EA orally notably alleviated post-surgical cognitive decline in older mice, a fact that was manifested in improved performance during maze tests. This enhancement in the behavioral performance of the EA-treated mice corresponded with the rejuvenation of IGF-1 signaling, a decrease in oxidative stress markers in the hippocampus (like MDA and carbonylated protein), and an increase in the activity of antioxidant enzymes such as SOD and CAT. Alongside these, we observed a decrease in microglia-driven neuroinflammation in the hippocampus, thus underscoring the antioxidant and anti-inflammatory roles of EA. Interestingly, when EA was given in conjunction with an IGF1R inhibitor, these benefits were annulled, accentuating the pivotal role that the IGF-1 pathway plays in the neuroprotective potential of EA. Hence, EA could serve as a potent candidate for safeguarding against PND in older patients by curbing oxidative stress and neuroinflammation through the activation of the IGF-1 pathway.

Hot-Carrier Cooling Regulation for Mixed Sn-Pb Perovskite Solar Cells.

The rapid relaxation of hot carriers leads to energy loss in the form of heat and consequently restricts the theoretical efficiency of single-junction solar cells; However, this issue has not received much attention in tin-lead perovskites solar cells. Herein, tin(II) oxalate (SnC2O4) is introduced into tin-lead perovskite precursor solution to regulate hot-carrier cooling dynamics. The addition of SnC2O4 increases the length of carrier diffusion, extends the lifetime of carriers, and simultaneously slows down the cooling rate of carriers. Furthermore, SnC2O4 can bond with uncoordinated Sn2+ and Pb2+ ions to regulate the crystallization of perovskite and enable large grains. The strongly reducing properties of the C2O4 2- can inhibit the oxidation of Sn2+ to Sn4+ and minimize the formation of Sn vacancies in the resulting perovskite films. Additionally, as a substitute for tin(II) fluoride, the introduction of SnC2O4 avoids the carrier transport issues caused by the aggregation of F- ions at the interface. As a result, the SnC2O4-treated Sn-Pb cells show a champion efficiency of 23.36%, as well as 27.56% for the all-perovskite tandem solar cells. Moreover, the SnC2O4-treated devices show excellent long-term stability. This finding is expected to pave the way toward stable and highly efficient all-perovskite tandem solar cells.

Association Between ß-Amyloid Accumulation and Incident Dementia in Individuals 80 Years or Older Without Dementia.

BACKGROUND AND OBJECTIVES: While the highest prevalence of dementia occurs in individuals older than 80 years, most imaging studies focused on younger populations. The rates of ß-amyloid (Aß) accumulation and the effect of Alzheimer disease (AD) pathology on progression to dementia in this age group remain unexplored. In this study, we examined the relationship between changes in Aß deposition over time and incident dementia in nondemented individuals followed during a period of 11 years. METHODS: We examined 94 participants (age 85.9 + 2.8 years) who had up to 5 measurements of Pittsburgh compound-B (PiB)-PET and clinical evaluations from 2009 to 2020. All 94 participants had 2 PiB-PET scans, 76 participants had 3 PiB-PET scans, 18 participants had 4 PiB-PET scans, and 10 participants had 5 PiB-PET scans. The rates of Aß deposition were compared with 120 nondemented individuals younger than 80 years (69.3 ± 5.4 years) from the Australian Imaging, Biomarker, and Lifestyle (AIBL) study who had 3 or more annual PiB-PET assessments. RESULTS: By 2020, 49% of the participants developed dementia and 63% were deceased. There was a gradual increase in Aß deposition in all participants whether they were considered Aß positive or negative at baseline. In a Cox model controlled for age, sex, education level, APOE-4 allele, baseline Mini-Mental State Examination, and mortality, short-term change in Aß deposition was not significantly associated with incident dementia (HR 2.19 (0.41-11.73). However, baseline Aß burden, cortical thickness, and white matter lesions volume were the predictors of incident dementia. Aß accumulation was faster (p = 0.01) in the older cohort (5.6%/year) when compared with AIBL (4.1%/year). In addition, baseline Aß deposition was a predictor of short-term change (mean time 1.88 years). DISCUSSION: There was an accelerated Aß accumulation in cognitively normal individuals older than 80 years. Baseline Aß deposition was a determinant of incident dementia and short-term change in Aß deposition suggesting that an active Aß pathologic process was present when these participants were cognitively normal. Consequently, age may not be a limiting factor for the use of the emergent anti-Aß therapies.

Advances in methods and techniques for the study of polysaccharide in vivo processes and immunomodulatory mechanisms / 药学学报

In recent years, polysaccharides have received much attention because of their high safety and good immunological activity. The study of polysaccharide in vivo process is a key scientific problem that needs to be solved for polysaccharide drug development. Some progress has been made in the field of polysaccharide pharmacokinetics and immunomodulation. However, due to the lack of both chromogenic and light-absorbing groups and the complex molecular structure of polysaccharides, the in vivo processes and immunomodulatory mechanisms of polysaccharides have been slow to be investigated. The effective combination of multiple techniques can break the bottleneck of difficult tracing and unknown immunomodulatory mechanism of polysaccharides in vivo, and promote the development and utilization of polysaccharides. In this paper, we systematically summarize the key techniques in the study of polysaccharide in vivo processes and immunomodulatory mechanisms in order to provide technical references and research ideas for the study of polysaccharide in vivo processes and immunomodulatory mechanisms.

An ERK5-PFKFB3 axis regulates glycolysis and represents a therapeutic vulnerability in pediatric diffuse midline glioma.

Metabolic reprogramming in pediatric diffuse midline glioma is driven by gene expression changes induced by the hallmark histone mutation H3K27M, which results in aberrantly permissive activation of oncogenic signaling pathways. Previous studies of diffuse midline glioma with altered H3K27 (DMG-H3K27a) have shown that the RAS pathway, specifically through its downstream kinase, extracellular-signal-related kinase 5 (ERK5), is critical for tumor growth. Further downstream effectors of ERK5 and their role in DMG-H3K27a metabolic reprogramming have not been explored. We establish that ERK5 is a critical regulator of cell proliferation and glycolysis in DMG-H3K27a. We demonstrate that ERK5 mediates glycolysis through activation of transcription factor MEF2A, which subsequently modulates expression of glycolytic enzyme PFKFB3. We show that in vitro and mouse models of DMG-H3K27a are sensitive to the loss of PFKFB3. Multi-targeted drug therapy against the ERK5-PFKFB3 axis, such as with small-molecule inhibitors, may represent a promising therapeutic approach in patients with pediatric diffuse midline glioma.

Corrigendum: Matching different-structured advertising pictorial metaphors with verbalization forms: incongruity-based evoked response potentials evidence.

[This corrects the article DOI: 10.3389/fpsyg.2023.1131387.].

Comparative Transcriptome Analysis Points to the Biological Processes of Hybrid Incompatibility between Brassica napus and B. oleracea.

Improving Brassica napus via introgression of the genome components from its parental species, B. oleracea and B. rapa, is an important breeding strategy. Interspecific hybridization between B. napus and B. rapa is compatible with high rate of survival ovules, while the hybridization between B. napus and B. oleracea is incompatible with the high occurrence of embryo abortion. To understand the diverse embryo fate in the two interspecific hybridizations, here, the siliques of B. napus pollinated with B. oleracea (AE) and B. rapa (NE) were employed for transcriptome sequencing at 8 and 16 days after pollination. Compared to NE and the parental line of B. napus, more specific differentially expressed genes (DEGs) (1274 and 1698) were obtained in AE and the parental line of B. napus at 8 and 16 days after pollination (DAP). These numbers were 51 and 5.8 times higher than the number of specific DEGs in NE and parental line of B. napus at 8 and 16 DAP, respectively, suggesting more complex transcriptional changes in AE. Most of DEGs in the terms of cell growth and cell wall formation exhibited down-regulated expression patterns (96(down)/131(all) in AE8, 174(down)/235(all) in AE16), while most of DEGs in the processes of photosynthesis, photorespiration, peroxisome, oxidative stress, and systemic acquired resistance exhibited up-regulated expression patterns (222(up)/304(all) in AE8, 214(up)/287(all) in AE16). This is in accordance with a high level of reactive oxygen species (ROS) in the siliques of B. napus pollinated with B. oleracea. Our data suggest that the disorder of plant hormone metabolism, retardation of cell morphogenesis, and the accumulation of ROS may be associated with hybrid incompatibility between B. napus and B. oleracea.

Percutaneous glycerol rhizolysis of the trigeminal ganglion for the treatment of idiopathic and classic trigeminal neuralgia: Outcomes and complications.

BACKGROUND AND PURPOSE: Patients with idiopathic trigeminal neuralgia (TN) with absent arterial contact or venous contact only and classic TN with morphological changes of the trigeminal nerve secondary to venous compression are not routinely recommended microvascular decompression at our institution. In patients with these anatomical subtypes of TN, limited data exists describing the outcomes of percutaneous glycerol rhizolysis (PGR) of the trigeminal ganglion (TG). METHODS: We performed a retrospective single-center cohort study and analyzed outcomes and complications after PGR of the TG. Clinical outcome after PGR of the TG was assessed via the Barrow Neurological Institute (BNI) Pain Scale. RESULTS: Forty-five patients underwent a total of 66 PGRs of the TG. At short-term follow-up, 58 procedures (87.9%) resulted in a BNI score of I (i.e., freedom from pain without medication). At a median follow-up of 3.07 years, 18 procedures (27.3%) resulted in a BNI score of I, 12 procedures (18.1%) resulted in BNI score of IIIa, and 36 procedures (54.5%) resulted in a BNI score of IIIb-V. The median length of freedom from pain without medication was 1.5 years. Eighteen procedures (27.3%) caused hypesthesia and two (3.0%) caused paresthesias. There were no serious complications. CONCLUSION: In patients with these anatomical subtypes of TN there was a high rate of short-term pain relief for the first 1-2 years and thereafter a large proportion of patients experienced pain relapse. In this patient group, PGR of the TG represents a safe procedure that is efficacious in the short term.

Types, functions and mechanisms of robot-assisted intervention for fall prevention: A systematic scoping review.

BACKGROUND: Any individual may experience accidental falls, particularly older adults. Although robots can prevent falls, knowledge of their fall-preventive use is limited. OBJECTIVE: To explore the types, functions, and mechanisms of robot-assisted intervention for fall prevention. METHODS: A systematic scoping review of global literature published from inception to January 2022 was conducted according to Arksey and O'Malley's five-step framework. Nine electronic databases, namely, PubMed, Embase, CINAHL, IEEE Xplore, the Cochrane Library, Scopus, Web of Science, PsycINFO, and ProQuest, were searched. RESULTS: Seventy-one articles were found with developmental (n = 63), pilot (n = 4), survey (n = 3), and proof-of-concept (n = 1) designs across 14 countries. Six types of robot-assisted intervention were found, namely cane robots, walkers, wearables, prosthetics, exoskeletons, rollators, and other miscellaneous. Five main functions were observed including (i) detection of user fall, (ii) estimation of user state, (iii) estimation of user motion, (iv) estimation of user intentional direction, and (v) detection of user balance loss. Two categories of mechanisms of robots were found. The first category was executing initiation of incipient fall prevention such as modeling, measurement of user-robot distance, estimation of center of gravity, estimation and detection of user state, estimation of user intentional direction, and measurement of angle. The second category was achieving actualization of incipient fall prevention such as adjust optimal posture, automated braking, physical support, provision of assistive force, reposition, and control of bending angle. CONCLUSIONS: Existing literature regarding robot-assisted intervention for fall prevention is in its infancy. Therefore, future research is required to assess its feasibility and effectiveness.

Matching different-structured advertising pictorial metaphors with verbalization forms: incongruity-based evoked response potentials evidence.

Many studies emphasize the need of verbally representing pictorial metaphors, but few have empirically investigated whether and how the particular verbalization form match different types of pictorial metaphors. Using evoked response potentials (ERP), a 3 (pictorial structure: fusion, juxtaposition, literal image) × 2 [verbalization form: A(is) B, A(is like) B] within-group experiment was conducted among 36 participants. ERPs were time-locked to the onset of the verb [/(is/is like)] of the metaphor sentence that follows a pictorial metaphor to detect the verbo-pictorial incongruity in metaphor comprehension. The incongruity-based ERP analysis showed that pictorial metaphors, when verbalized in two forms, all induced frontal N1 effect, regardless of pictorial structures, only with a larger N1 amplitude for literal images in "A(is) B." A central stronger P2 was observed in "A(is like) B" for three structures. Despite a general elicitation of posterior P3 in all conditions, a larger P3 was found for juxtapositions verbalized in "A(is like) B" and for literal images verbalized in "A(is) B." There was no significant difference between two verbalization forms for fusion-structured pictorial metaphors. These findings suggest: (1) verbo-pictorial metaphors could induce incongruity-based attention; (2) higher verbo-pictorial semantic congruity and relatedness, indexed by stronger P2 and P3, confirmed "A(is like) B" to be the more effective verbalization form in representing pictorial metaphors, specifically for juxtaposition-structured pictorial metaphors; (3) for non-metaphor advertising pictures, verbal metaphor showed an interference effect. The study not only reveals the neuro-cognitive mechanism of processing verbo-pictorial metaphors, but also offers neural reference for the design of effective multi-modal metaphor by finding an optimal match between PMs and verbalization forms.

Health risk study of cadmium, chromium, lead and arsenic in reservoir water of Changzhou, China.

Accurately assessing the health risks of human exposure to heavy metals via water is of great importance for performing targeted health risk prevention measures. To better understand the concentration characteristics and potential harm to human health of cadmium, chromium, lead and arsenic in the main drinking water-type reservoirs of Changzhou city, we collected samples from the Haidi Reservoir, Dongjin Reservoir, Xinfushan Reservoir, Maodong Reservoir and Xiangyang Reservoir of Changzhou in the summer of 2019. The results showed that the daily average comprehensive exposure level of metals was much lower than the provisional tolerated daily intake (PTDI), i.e., Cd: 1 µg kg-1 d-1; Cr: 3 µg kg-1 d-1; Pb: 3.57 µg kg-1 d-1; and As: 2.14 µg kg-1 d-1. The comprehensive non-carcinogenic risk levels of four metals under water-drinking exposure and water-skin exposure routes ranged from 4.68E - 3 to 1.69E - 1, and the carcinogenic risk ranged from 2.09E - 5 to 7.30E - 5, which were all at acceptable risk levels. Although lead and chromium were present at acceptable health risk levels, they still represented the main pollutants of potential health risk in the local water environment from a non-carcinogenic or carcinogenic perspective, and they should be listed as the primary targets for water environmental risk management.

Effects of oral ß-caryophyllene (BCP) treatment on perioperative neurocognitive disorders: Attenuation of neuroinflammation associated with microglial activation and reinforcement of autophagy activity in aged mice.

Perioperative neurocognitive disorders (PND) are a constellation of cognitive impairments that arise following surgical procedures and anesthesia, with a higher incidence in elderly patients. PND is deeply entwined with microglia-mediated neuroinflammation and disrupted autophagy. ß-caryophyllene (BCP) is a natural terpene that occurs widely in dietary plants, and possesses robust anti-inflammatory properties by selectively activating CB2 receptors (CB2R). Accordingly, the present study endeavors to investigate the potential of BCP in ameliorating PND in aged mice, by mitigating hippocampal neuroinflammation and improving autophagy. In this study, an abdominal surgery was utilized to induce perioperative neurocognitive disorders (PND) in aged mice. BCP was administered orally at a dosage of 200 mg/kg for seven consecutive days prior to the scheduled surgery. In order to explore the relationship between BCP and CB2 receptors (CB2R), a co-administration of intraperitoneal injections of the CB2R antagonist AM630 was implemented, 30 min preceding the oral gavage of BCP. Postoperative cognitive functions were assessed using Morris water maze (MWM) tests. The extent of hippocampal inflammation was examined by measuring the microglial marker Iba-1 protein levels, Iba-1 and GFAP immunoactivity, as well as IL-1ß and IL-6 concentrations. Evaluation of autophagy activity was conducted based on the ratio of LC3B2/LC3B1 and protein levels of Beclin-1, p62, and phospho-mTOR (p-mTOR). After being orally administered BCP, the compromised behavioral performance of abdominal surgical interventions on aged mice was alleviated. This was evident by the extended escape latency, reduced time spent in the target quadrant, and fewer platform crossings observed through MWM testing. While hippocampal CB2R mRNA or protein expression remained unaffected by the abdominal surgical procedure, their levels were significantly upregulated in mice that were administered BCP. Moreover, the oral administration of BCP was able to reduce neuroinflammation in response to microglia activation, as evidenced by the decreased levels of Iba-1 protein and immunoactivity, as well as the reduction of IL-1ß and IL-6 concentrations. Additionally, BCP intensified autophagic activity, as detected by increased LC3B2/LC3B1 ratio and Beclin-1 protein levels, coupled with decreased levels of p62 and p-mTOR in the hippocampus of aged mice. Conversely, the treatment of AM630 ameliorated the suppressive effect of BCP triggered by the neuroinflammation caused by microglial activation post-surgery in aged mice (increased Iba-1 protein levels and immunoactivity, accompanied by higher IL-1ß and IL-6 concentrations). Furthermore, the pro-autophagy effect of BCP on aged mice following surgery was partially blocked by AM630, culminating in decreased LC3B2/LC3B1 ratio and Beclin-1 protein levels. However, the levels of p62 and p-mTOR remained unchanged by AM630. Our investigation unveils the remarkable therapeutic benefits of oral BCP administration for managing PND in aged mice through the attenuation of neuroinflammation associated with microglial activation and the fortification of autophagy activity. Hence, BCP holds great promise as a formidable candidate englobing various potential physiological mechanisms that would mitigate cognitive decline associated with aging.

Genome-Wide Splicing Quantitative Expression Locus Analysis Identifies Causal Risk Variants for Non-Small Cell Lung Cancer.

Alternative RNA splicing is an essential mechanism linking genetic variation to human diseases. While the signals from genome-wide association studies (GWAS) have been linked to expression quantitative trait loci (eQTL) in previous studies, further work is needed to better elucidate the relationship to other genetic regulatory mechanisms, such as splicing QTLs (sQTL). Here, we performed a genome-wide sQTL analysis to identify variants that might affect RNA splicing in 1,010 non-small cell lung cancer (NSCLC) samples from The Cancer Genome Atlas. The identified sQTLs were largely independent of eQTLs and were predominantly enriched in exonic regions, genetic regulatory elements, RNA-binding protein (RBP) binding sites, and known NSCLC risk loci. In addition, target genes affected by sQTLs (sGenes) were involved in multiple processes in cancer, including cell growth, apoptosis, metabolism, immune infiltration, and drug responses, and sGenes were frequently altered genetically in NSCLC. Systematic screening of sQTLs associated with NSCLC risk using GWAS data from 15,474 cases and 12,375 controls identified an sQTL variant rs156697-G allele that was significantly associated with an increased risk of NSCLC. The association between the rs156697-G variant and NSCLC risk was further validated in two additional large population cohorts. The risk variant promoted inclusion of GSTO2 alternative exon 5 and led to higher expression of the GSTO2 full-length isoform (GSTO2-V1) and lower expression of the truncated GSTO2 isoform (GSTO2-V2), which was induced by RBP quaking (QKI). Mechanistically, compared with GSTO2-V1, GSTO2-V2 inhibited NSCLC cells proliferation by increasing S-glutathionylation of AKT1 and thereby functionally blocking AKT1 phosphorylation and activation. Overall, this study provides a comprehensive view of splicing variants linked to NSCLC risk and provides a set of genetic targets with therapeutic potential. SIGNIFICANCE: Analysis of sQTL reveals the role of genetically driven mRNA splicing alterations in NSCLC risk and elucidates that rs156697 variant impacts risk by altering GSTO2 splicing.

[Early clinical application of Mako robot-assisted total knee arthroplasty in knee osteoarthritis].

OBJECTIVE: To investigate the early efficacy of Mako robot-assisted total knee arthroplasty (TKA) in the treatment of knee osteoarthritis (KOA) and summarize the initial application experience. METHODS: Retrospective analysis of 73 patients with KOA treated with Mako robot-assisted TKA from June 2021 to December 2021. There were 16 males and 57 females, aged from 54 to 81 years old with an average of (67.8±6.6) years old. The hip knee and ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), lateral femoral component angle (LFCA) and lateral tibial component angle (LTCA) were recorded and analyzed. WOMAC score and KSS were used to compare the functional recovery of patients preoperatively, 3 and 6 months postoperatively. RESULTS: All the 73 patients were successfully treated without serious complications such as vascular and nerve injury, and all the incisions healed well at stageⅠwithout infection. The patients were followed up from 4 to 11 months with an average of (7.0±2.7) months, and the satisfaction rate of the last follow-up was 90.41% (66/73). WOMAC scores were (23.1±5.4) at 3 months and (14.8±4.1) at 6 months postoperatively. KSS clinical scores were ( 76.1±4.0) at 3 months and (82.1±3.7) at 6 months postoperatively;KSS functional scores were (74.3±3.1) at 3 months and (78.6±2.1) at 6 months after operation. Postoperative imaging showed good position of the prosthesis, HKA angle was (178.5±2.1)°, LDFA was (91.2±1.8)°, MPTA was(89.9±1.5) °, LFCA was (7.6±3.1)°, LTCA was (88.2±1.1)°. The mechanical axis within ±3° in sixty cases(82.2%), and the mechanical axis within ±6° in all the patients. CONCLUSION: Mako robot-assisted TKA is a safe and effective surgery in the treatment of knee osteoarthritis, which exhibited good efficacy in the correction of lower limb alignment, soft tissue balance and improvement of knee function. The long-term efficacy needs further follow-up observation.

Long-term Benefits for Younger Patients with Aggressive Immediate Intervention following Severe Traumatic Brain Injury: A Longitudinal Cohort Analysis of 175 Patients from a Prospective Registry.

BACKGROUND: The prevalence of traumatic brain injury (TBI) continues to rise, in part as a reflection of a growing elderly population. Concomitantly, nihilism may exist following substantial neurotrauma from a myriad of commonplace mechanisms, such as traffic incidents, assaults, or falls. OBJECTIVE: This study assesses long-term outcomes following aggressive surgical intervention with invasive neuromonitoring to guard against nihilism, especially for patients with advantageous characteristics such as younger age. METHODS: A consecutive series of patients with severe TBI treated between 2008 and 2018 and enrolled into the Brain Trauma Research Center (BTRC) database, an Institutional Review Board (IRB 19030228) approved prospective, longitudinal cohort study, were extracted. Demographic and clinical data were analyzed. Long-term functional outcome was recorded with the eight-point Glasgow Outcome Scale-Extended (GOS-E) score at 3-, 6-, 12-, and 24-months by trained, qualified neuropsychology technicians. Chi-squared and analysis of variance tests were used to evaluate the relationship of age groups between different variables. RESULTS: For this analysis, 175 patients with severe TBI who were enrolled in the BTRC database and required decompressive hemicraniectomy during the study period were included. Over one-third of the patients with a severe TBI, who were aged 35 years and younger, had a favorable outcome. CONCLUSIONS: Despite enduring a severe TBI, a substantial percentage of younger patients achieved favorable outcomes following aggressive treatment. As such, establishing a prognosis should be deferred to allow for recovery via individualized rehabilitation, multidisciplinary support, and community reintegration programs to cope with various long-term psychological, cognitive, and functional disabilities.