psoResNet: An improved PSO-based residual network search algorithm.

Neural Architecture Search (NAS) methods are widely employed to address the time-consuming and costly challenges associated with manual operation and design of deep convolutional neural networks (DCNNs). Nonetheless, prevailing methods still encounter several pressing obstacles, including limited network architecture design, excessively lengthy search periods, and insufficient utilization of the search space. In light of these concerns, this study proposes an optimization strategy for residual networks that leverages an enhanced Particle swarm optimization algorithm. Primarily, low-complexity residual architecture block is employed as the foundational unit for architecture exploration, facilitating a more diverse investigation into network architectures while minimizing parameters. Additionally, we employ a depth initialization strategy to confine the search space within a reasonable range, thereby mitigating unnecessary particle exploration. Lastly, we present a novel approach for computing particle differences and updating velocity mechanisms to enhance the exploration of updated trajectories. This method significantly contributes to the improved utilization of the search space and the augmentation of particle diversity. Moreover, we constructed a crime-dataset comprising 13 classes to assess the effectiveness of the proposed algorithm. Experimental results demonstrate that our algorithm can design lightweight networks with superior classification performance on both benchmark datasets and the crime-dataset.

Residual varus alignment after posterior-stabilized total knee arthroplasty limits medial soft tissue remodeling.

BACKGROUND: Proper lower limb alignment and soft tissue balance are significant indicators to measure the success of total knee arthroplasty (TKA). Previous studies have confirmed that soft tissue relaxation around the knee after TKA will change over time; however, the relationship between lower limb alignment and soft tissue balance after TKA remains unclear. We studied (1) whether the change of soft tissue balance around the knee with time after posterior-stabilized (PS) TKA would affect the alignment of the lower limbs; (2) Whether the accuracy of lower limb alignment during PS TKA affects postoperative soft tissue remodeling. METHODS: In this study, 100 patients were recruited after PS TKA. Among them, 50 patients with a hip knee ankle (HKA) angle of ≤ ± 3° were set as the neutral group, and 50 patients with an HKA angle of > ± 3° were set as the deviation group. The imaging results measured the HKA angle before the operation as well as the HKA, varus, and valgus angles at 1, 3, 6, 12, and 24 months after TKA. Clinical assessment included range of motion (ROM), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Society Score (KSS). RESULTS: Eight people were excluded from the study. After the exclusion, the study enrolled 47 patients in the neutral group and 45 patients in the deviant group and were followed for up to 2 years. There was no statistical significance in mean varus angles as well as HKA angle changes during the follow-up phase of each groups (P > 0.05). The mean valgus angles of the patients in the neutral group group were 2.47°, 3.45°, 3.63°, 3.60° and 3.63°, and in the deviation group were 2.45° (P = 0.841), 2.88° (P < 0.001), 3.07° (P < 0.001), 3.06° (P < 0.001), and 3.10° (P < 0.001). ROM, WOMAC and KSS of the two groups were significantly improved after operation, with no difference between the two groups. CONCLUSION: This study shows that whether the alignment is accurate or not in the early stage after TKA, the relaxation of the medial and lateral soft tissues of the knee joint change; however, this change will not significantly affect the alignment of the lower limbs. Postoperative residual varus deformity limits medial soft tissue remodeling. LEVEL OF EVIDENCE: III.

Reliability and validity of a semi-quantitative food frequency questionnaire: dietary intake assessment among multi-ethnic populations in Northwest China.

BACKGROUND: Few multi-ethnic dietary culture-sensitive food frequency questionnaires (FFQ) have been developed due to the complexity and diversity of cooking methods and styles. This study aimed to develop and validate a specific FFQ among multi-ethnic groups in Northwest China. METHODS: In the reliability study, 139 participants aged 20-65 completed two identical FFQs separated by 3 months. The relative validation of the FFQ was assessed by three 24-h recalls (24HR) employed in the interval of two FFQs, as a reference. Stratified analyses were also conducted by the major ethnic groups (Han nationality or Ethnic minority). RESULTS: For reproducibility, the median (range) of Spearman's correlation coefficients (SCC) was 0.71 (0.43-0.84) for nutrients. The intra-class correlation coefficients (ICC) covered a spectrum from 0.39 to 0.78 (median: 0.64). Meanwhile, the weighted kappa values ranged from 0.11 to 0.64. For validity, the median (range) of Pearson's correlation coefficients derived from the energy unadjusted and the adjusted values between FFQ and 24HR were 0.61 (0.12-0.79) and 0.56 (0.12-0.77), respectively. The results of correlation coefficients were similar between the two ethnic groups. Moreover, the Bland-Altman plots likewise demonstrated a satisfactory level of agreement between the two methods. CONCLUSIONS: The FFQ showed acceptable reproducibility and moderate relative validity for evaluating dietary intake among multi-ethnic groups in northwest China. It could be a credible nutritional screening tool for forthcoming epidemiological surveys of these populations.

The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by Immunomodulation.

Gastric carcinoma is a frequently detected malignancy worldwide, while its mainstream drugs usually result in some adverse reactions, including immunosuppression. λ-carrageenan oligosaccharides (COS) have attracted increasing attention as potential anticancer agents due to their ability to enhance immune function. Our current work assessed the antitumor mechanism of λ-COS using BGC-823 cells. Our findings indicated that λ-COS alone did not have a significant impact on BGC-823 cells in vitro; however, it was effective in inhibiting tumor growth in vivo. When THP-1 cells were pre-incubated with λ-COS and used to condition the medium, BGC-823 cells in vitro displayed a concentration-dependent induction of cell apoptosis, nuclear damage, and the collapse of mitochondrial transmembrane potential. These findings suggested that the antineoplastic effect of λ-COS was primarily due to its immunoenhancement property. Treatment with λ-COS was found to significantly enhance the phagocytic capability of macrophages, increase the secretion of TNF-α and IFN-γ, and improve the indexes of spleen and thymus in BALB/c mice. In addition, λ-COS was found to inhibit the growth of BGC-823-derived tumors in vitro by activating the Par-4 signaling pathway, which may be stimulated by the combination of TNF-α and IFN-γ. When used in combination with 5-FU, λ-COS demonstrated enhanced anti-gastric carcinoma activity and improved the immunosuppression induced by 5-FU alone. These findings suggested that λ-COS could be used as an immune-modulating agent for chemotherapy.

Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome.

Background: Ulcerative colitis (UC) and irritable bowel syndrome (IBS) share various similarities in clinical symptoms, pathogenesis, and treatment. UC concurrent IBS tends toward more severe symptoms and worse prognosis, and promising feasible therapies for the overlapping symptoms remains a challenge. Rhubarb peony decoction (RPD) is a well-known traditional Chinese medicine that has been widely applied in treating UC. RPD may exert extensive therapeutic effects on both IBS and UC. However, the common mechanism of its treatment remains unclear. We aimed to assess the potential pharmacological mechanism of RPD in the treatment of overlapping IBS and UC. Methods: The active components and targets of RPD were retrieved from ETCM, TCMSP, BATMAN-TCM, and TCM databases. The disease targets were screened by searching the DrugBank, OMIM, TTD, and PharmGKB databases. PPI network analysis was performed and visualized via the STRING platform and Cytoscape software. GO and KEGG enrichment analyses of the hub genes of RPD were predicted to elucidate the potential molecular mechanism. Subsequently, molecular docking was carried out to verify the combination of active compounds with core targets. Results: By integrating all targets of RPD and disease, a total of 31 bioactive ingredients were identified including quercetin, kaempferol, aloe-emodin, beta-sitosterol, and (+)-catechin, etc. JUN, TP53, MAPK1, RELA, MYC, and ESR1 were explored as potential therapeutic targets among 126 common drug-disease-related targets. They were enriched in the AGE-RAGE signaling pathway in diabetic complications, as well as the NF-kappa B signaling pathway and MAPK signaling pathway. Additionally, some active ingredients were identified as candidates for binding to the hub targets via molecular docking, further suggesting their anti-inflammatory and antioxidative properties. Conclusion: RPD may exert the overall treatment effect for UC and IBS overlap syndrome via the biological mechanism of "multi-ingredients, multi-targets, and multi-pathways" on inflammation, oxidative stress, immune, oncogenicity, and gut microbiota dysbiosis.

Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells.

As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson's disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA). Supplementation with antioxidants early in PD can effectively prevent neurodegeneration and inhibit apoptosis in dopaminergic neurons. At present, the effect of fucoxanthin in improving the adverse effects triggered by long-term l-DA administration in PD patients is unclear. In the present study, we found that fucoxanthin can reduce cytotoxicity and suppress the high concentration of l-DA (200 µM)-mediated cell apoptosis in the 6-OHDA-induced PC12 cells through improving the reduction in mitochondrial membrane potential, suppressing ROS over-expression, and inhibiting active of ERK/JNK-c-Jun system and expression of caspase-3 protein. These results were demonstrated by PD mice with long-term administration of l-DA showing enhanced motor ability after intervention with fucoxanthin. Our data indicate that fucoxanthin may prove useful in the treatment of PD patients with long-term l-DA administration.

Food additive sodium bisulfite induces intracellular imbalance of biothiols levels in NCM460 colonic cells to trigger intestinal inflammation in mice.

Sulfites and other preservatives are considered food additives to prevent pathogen growth in food, and they are generally regarded as safe since the late 1950s. However, the possible effects of sulfites on potential damage to host intestinal tissue remain largely unexplored. Given that endogenous sulfite mainly comes from the metabolism of biothiol, we attempted to clarify the relationship among biothiol levels, gut and food additives sulfite, including sodium bisulfite (NaHSO3), and the possible mechanism of sulfite affecting the intestine. In the present study, the NaHSO3 treatments markedly increased the homocysteine (Hcy) level but decreased the cysteine (Cys) level by promoting the expression of Hcy synthase and inhibiting the activities of cystathionine ß-synthase and cystathionine γ-lyase in NCM460 cells. The level of methionine (Met) was not significantly changed, but NaHSO3 promoted ROS-mediated NF-κB signaling pathway, and increased the expressions of proinflammatory cytokines by regulating the levels of Hcy and Cys in NCM460 cells. Vitamin B6 (VB6) supplementation successfully ameliorated NaHSO3-induced damage in NCM460 cells and the colon of Balb/c mice. Altogether, our study provided valuable insights into the safety evaluation of food preservatives. Besides, VB6 could be used as a promising candidate in novel therapies for sodium bisulfite-induced intestinal inflammation.

PDK1 promotes apoptosis of chondrocytes via modulating MAPK pathway in osteoarthritis.

3-Phosphoinositide dependent protein kinase-1 (PDK1), a serine threonine kinase, belongs to the AGC kinase family and is associated with apoptosis. The aim of this study was to investigate the expression of PDK1 (3-Phosphoinositide dependent protein kinase-1) in articular cartilage with osteoarthritis (OA) and to analyze the relationship between PDK1 and chondrocyte apoptosis. Immunohistochemistry and RT-PCR analysis showed that the expression of PDK1 in articular cartilage of OA patients and healthy controls. IL-1ß-stimulated SW1353 cells were used to imitate the OA-like chondrocyte injury in vitro, and IL-1ß-induced the expression of PDK1, apoptotic markers(PARP, caspase-3), and phosphorylated p38 were detected by Western blot. The co-localization of PDK1 and Cleaved-caspase3 was confirmed through immunofluorescence. Knocking down PDK1 expression through PDK1 siRNA. Western blot was performed to detect the knockdown efficiency of PDK1 and the impact of PDK1 knockout on IL-1ß-induced expression of apoptotic markers and phosphorylated p38 in SW1353 cells. Flow Cytometry-Based Annexin V/PI Staining was used to exam chondrocyte apoptosis. Our experimental results suggested that PDK1 may promote chondrocyte apoptosis in OA via p38 MAPK signaling pathway.

Vacuolar Protein Sorting 4B (VPS4B) Regulates Apoptosis of Chondrocytes via p38 Mitogen-Activated Protein Kinases (MAPK) in Osteoarthritis.

To aim of this study is to investigate the expression of VPS4B (vacuolar protein sorting 4B) in articular cartilage with osteoarthritis (OA) and to analyze the relationship between VPS4B and chondrocyte apoptosis. We established an OA rat model by the MLI (meniscal/ligamentous injury) modeling method, and we observed the expression of VPS4B in articular cartilage through immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Human SW1353 chondrosarcoma cells were treated with IL-1ß to mimic the OA-like chondrocyte injury in vitro, and Western blot was employed to examine the IL-1ß-induced expression of VPS4B, phosphorylated p38, and apoptotic markers, namely active caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP). The co-localization of VPS4B and active caspase 3 was confirmed through immunofluorescence. We knocked down VPS4B expression through RNA interference. Western blot was carried out to detect the knockdown efficiency of VPS4B and evaluate its effects on IL-1ß-stimulated expression of apoptotic markers and phosphorylated p38 in SW1353 cells. Annexin V/propidium iodide (PI) staining was used to detect chondrocyte apoptosis. VPS4B expression was significantly upregulated in articular cartilage of OA rat model. IL-1ß stimulation increased the expression of VPS4B, apoptotic markers, and phosphorylated p38 in SW1353 cells. VPS4B co-localized with active caspase 3 in IL-1ß-treated SW1353 cells. VPS4B inhibition significantly reduced IL-1ß-stimulated expression of apoptotic markers and phosphorylated p38 in SW1353 cells. Moreover, flow cytometry assay demonstrated that VPS4B knockdown alleviated IL-1ß-induced apoptosis. Our results suggested that VPS4B might facilitate chondrocyte apoptosis in OA via p38 MAPK signaling pathway. This study may provide a novel insight into the pathophysiology of OA and a potential therapeutic target for its treatment.

SGTB Promotes the Caspase-Dependent Apoptosis in Chondrocytes of Osteoarthritis.

The purpose of this study is to investigate the expression of small glutamine-rich tetratricopeptide repeat (TPR)-containing ß (SGTB) in articular cartilage of osteoarthritis (OA) and analyze the relationship between SGTB and chondrocyte apoptosis. We established an OA rat model by the meniscal/ligamentous injury (MLI) modeling method and observed the expression of SGTB in articular cartilage by immunohistochemistry and RT-PCR. Human SW1353 chondrosarcoma cells were treated with interleukin-1ß (IL-1ß) to mimic the OA-like chondrocyte injury in vitro, and Western blot was employed to examine the IL-1ß-induced expression of SGTB and active caspase-3. The co-localization of SGTB and active caspase-3 was confirmed by immunofluorescence. We knocked down SGTB expression by RNA interference (RNAi) and overexpressed SGTB by plasmid transfection. Western blot was carried out to detect the knockdown/overexpressing efficiency of SGTB and evaluate its effects on IL-1ß-stimulated expression of active caspase-3 in SW1353 cells. Annexin V/propidium iodide staining was used to detect chondrocyte apoptosis. Then, Western blot was carried out to examine the IL-1ß-induced expression of Hsp70 and evaluate SGTB effects on IL-1ß-stimulated expression of Hsp70 in SW1353 cells. SGTB expression was significantly up-regulated in articular cartilage of OA rat model. IL-1ß stimulation increased the expression of SGTB and active caspase-3 in SW1353 cells. SGTB co-localized with active caspase-3 in IL-1ß-treated SW1353 cells. SGTB inhibition significantly reduced IL-1ß-stimulated expression of active caspase-3 in SW1353 cells. In line with this, overexpressing SGTB via Myc-SGTB transfection increased the active caspase-3 level in IL-1ß-stimulated SW1353 cells. Moreover, flow cytometry assay demonstrated that SGTB knockdown alleviated IL-1ß-induced apoptosis, but it was increased in SW1353 cells that overexpressed SGTB. Overexpressing SGTB via Myc-SGTB transfection decreased the Hsp70 level in IL-1ß-stimulated SW1353 cells. Our results suggested that SGTB positively regulate the activation of caspase-3 by negatively regulating the activity of Hsp70 and might promote chondrocyte apoptosis in OA. This study may provide a novel insight into the pathophysiology of OA and a potential therapeutic target for its treatment.

Sam68 Promotes NF-κB Activation and Apoptosis Signaling in Articular Chondrocytes during Osteoarthritis.

OBJECTIVES: To investigate the expression of Sam68 in articular cartilage of knee osteoarthritis (OA) and the relationship between Sam68 and NF-κB activation and apoptosis signaling in OA articular chondrocytes. METHODS: Sam68 expression in normal and osteoarthritic cartilage was assessed by immunohistochemistry and RT-PCR on both meniscal/ligamentous injury (MLI)-induced OA rat model and the clinical human OA cartilage tissues. Sam68 expression in chondrocytes under tumor necrosis factor-alpha (TNF-α) stimuli was also assessed by immunoblot. Inhibiting Sam68 in chondrocytes under TNF-α stimuli was conducted using small interfering RNA (siRNA) and its influence on the expression of apoptotic marker and catabolic genes was examined by immunoblot. The mechanism of how Sam68 stimulates NF-κB activity was determined by co-immunoprecipitation and immunoblot analysis of nuclear and cytoplasmic fractions of TNF-α-treated chondrocytes for p65 and Sam68. RESULTS: Sam68 expression was increased in OA cartilage tissues and chondrocytes under TNF-α stimuli. Inhibition of Sam68 by siRNA significantly decreased the expression of apoptotic markers (cleaved caspase-3 and cleaved PARP) in chondrocytes following TNF-α-stimulation. Sam68 knockdown suppressed Iκ-B degradation and p65 nuclear transportation in TNF-α-treated chondrocytes, indicating a suppressed NF-κB activation. Upon TNF-α exposure, the nuclear transportation of Sam68 and its interaction with p65 was detected in chondrocytes. Furthermore, Sam68 knockdown also alleviated the TNF-α-induced catabolic marker (MMP13, ADAMTS5, iNOS and IL-6) expression. CONCLUSIONS: The highly expressed Sam68 promotes NF-κB signaling activation, catabolic gene expression and cellular apoptosis in TNF-α-treated chondrocytes, which may provide better insights into the pathophysiology of OA and a potential target for its treatment.

KPNA2 interacts with P65 to modulate catabolic events in osteoarthritis.

OBJECTIVE: Karyopherin alpha 2 (KPNA2) is a member of the importin α family, which acts as an adaptor to deliver P65 to the nucleus by recognizing the classic nuclear localization signal (NLS) of the cargo protein, and which has been reported as being involved in the pathogenesis of many diseases. This study was undertaken to determine the expression and possible functions of KPNA2 in osteoarthritis (OA). METHODS: KPNA2 expression in cartilage tissues of OA patients and normal controls was detected by RT-PCR and immunohistochemistry. SW1353 cells were stimulated with IL-1ß to establish the chondrocyte injury model in vitro. The expression of KPNA2 and catabolic genes in IL-1ß-treated SW1353 cells were determined by Western blot. The interaction between KPNA2 and P65 was analyzed by co-immunoprecipitation, the subcellular distribution and transportation of P65 were detected by the subcellular fractionation followed by immunoblot analysis and immunofluorescence. Furthermore, we used RNA interference to analyze the role of KPNA2 in IL-1ß-induced P65 nuclear importation and MMP13, ADAMTS-5 expression in SW1353 cells. RESULTS: Cartilage expression of KPNA2 was higher in patients with OA compared with normal controls and mainly locating in chondrocytes. In IL-1ß-treated SW1353 cells, up-regulation of KPNA2 was accompanied by the elevated expression of the catabolic marker protein levels, including MMP13 and ADAMTS-5, and increased NF-κB P65 nuclear importation. Knock-down of KPNA2 resulted in decreased catabolic marker protein levels in IL-1ß-treated SW1353 cells. KPNA2 interacted with p65, and loss of KPNA2 caused decreased nuclear translocation of the active p50/p65 NF-κB complex. CONCLUSIONS: These findings suggested that KPNA2 may promote NF-κB activation via facilitating P65 nuclear transportation, and thus subsequently accelerate the catabolic events of osteoarthritis.