Association of thyroid hormone with osteoarthritis: from mendelian randomization and RNA sequencing analysis.

BACKGROUND: The relationship between thyroid hormone (TH) levels in vivo and osteoarthritis (OA) remains inconclusive. This study aims to investigate the association between TH levels and OA, analyze the effect of triiodothyronine on hypertrophic chondrocyte differentiation and OA progression, and identify potential target genes of triiodothyronine in OA to evaluate its diagnostic value. METHODS: Two-sample mendelian randomization method was used to probe the causal links between hyperthyroidism and OA. Differentially expressed genes (DEGs) from two RNA-sequencing data in Gene Expression Omnibus (GSE199847 and GSE114007) and enrichment analysis of DEGs (166 commonly upregulated genes and 71 commonly downregulated genes of GSE199847 and GSE114007) was performed to analyze the effect of triiodothyronine (T3) on hypertrophic chondrocyte differentiation and OA. C28/I2 cells treated with T3 and reverse transcription and quantitative real-time polymerase chain reaction were used to validate T3 targeted genes. The diagnostic performance of target genes was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). RESULTS: There was a positive causal association between hyperthyroidism and OA (IVW result, OR = 1.330, 95% CI 1.136-1.557, P = 0.0004). Weighted median and Weighted mode analysis also demonstrated that hyperthyroidism had a positive causal association with OA (p < 0.05, OR > 1). Bioinformatics analysis indicated T3 can partially induce the emergence of late hypertrophic chondrocyte and promote OA through extracellular matrix organization, blood vessel development, skeletal system development and ossification. Post-T3 treatment, MAFB, C1QTNF1, COL3A1 and ANGPTL2 were significantly elevated in C28/I2 cells. ROC curves in GSE114007 showed that AUC of all above genes were ≥ 0.7. CONCLUSIONS: This study identified that hyperthyroidism has a positive causal association with OA by MR analysis. T3 induced hypertrophic chondrocytes promote OA progression by upregulating genes such as MAFB, C1QTNF1, COL3A1 and ANGPTL2, which can also serve as OA diagnosis.

Fractionally spaced nonlinear Tomlinson-Harashima precoding with weight clustering for C-band 100†Gbaud/λ PAM-4 transmission.

A nonlinear Tomlinson-Harashima precoding (NTHP) scheme has been verified for its capability to effectively address both the linear and nonlinear inter-symbol interferences (ISIs) arising in the intensity-modulation direct-detection (IM-DD) fiber optics transmission. Nevertheless, the application of the NTHP scheme may significantly increase the number of levels for the intensity modulated signals, resulting in the reduction of both eye width and receiver sensitivity. Here, we propose a fractionally spaced NTHP with a weight clustering (FS-NTHP-WC) scheme. Consequently, an accurate ISI feedback can be obtained to enlarge the eye width; meanwhile a hardware-efficient implementation without the equalization penalty can be achieved by weight clustering and pruning. When the C-band 100 Gbaud/λ PAM-4 signals are transmitted, our proposed FS-NTHP-WC scheme not only can achieve 0.25 dB and 0.5 dB gains of receiver sensitivity under back-to-back (B2B) and 2-km standard single-mode fiber (SSMF) transmission conditions, respectively, but can also cut down the computational complexity by 90% and 76% in terms of the number of multiplications and additions, respectively, in comparison with the NTHP scheme.

Application of the New Irrigation Protocol to Reduce Recurrence Rate in the Management Of Periprosthetic Joint Infection.

OBJECTIVE: Irrigation is a conventional treatment for acute and chronic periprosthetic joint infections (PJI). However, there has been no unified standard for irrigation during surgery for PJI in the past, and the efficacy is uncertain. The purpose of this study is to create a new irrigation protocol to enhance the infection control rate and reduce the postoperative recurrence rate of PJI patients. METHODS: We conducted a single-institution retrospective review with a total of 56 patients who underwent revision total hip or knee arthroplasties due to PJI from January 2011 to January 2022. Conventional irrigation (CI) was used in 32 cases, and standard operating procedure of irrigation (SOPI) was used in 24. The CI protocol carries out an empirical irrigation after debridement, which is quite random. Our SOPI protocol clearly stipulates the soaking concentration and time of hydrogen peroxide and povidone-iodine. The irrigation is carried out three times, and tissue samples are taken from multiple parts before and after irrigation, which are sent for microbial culture. The important statistical indicators were the rate of positive microbiological culture and postoperative recurrence rate with an average follow-up of 24 average months. RESULTS: The drainage volume was lower in the SOPI group than in the CI group on postoperative day 3 (p < 0.01) and 7 (p = 0.016). In addition, the percentage of positive microbiological cultures after the third irrigation was less than that before (p < 0.01) and after (p < 0.01) the first irrigation. The most common causative organism was Staphylococcus aureus, which was detected in 25.0% and 12.5% of the SOPI and CI groups, respectively. The failure rate at the final follow-up was 8.3% and 31.3% (p = 0.039) for the SOPI and CI groups, respectively. CONCLUSION: Compared with the traditional CI method, SOPI standardized the soaking time of hydrogen peroxide and povidone-iodine, increased the frequency of and irrigation, and proved that microorganisms were almost completely removed through the microbial culture of multiple tissues. SOPI has the potential to become a standardized irrigation process worthy of promotion, effectively reducing the postoperative recurrence rate of PJI patients.

Distance-Aware Occlusion Detection with Focused Attention.

For humans, understanding the relationships between objects using visual signals is intuitive. For artificial intelligence, however, this task remains challenging. Researchers have made significant progress studying semantic relationship detection, such as human-object interaction detection and visual relationship detection. We take the study of visual relationships a step further from semantic to geometric. In specific, we predict relative occlusion and relative distance relationships. However, detecting these relationships from a single image is challenging. Enforcing focused attention to task-specific regions plays a critical role in successfully detecting these relationships. In this work, (1) we propose a novel three-decoder architecture as the infrastructure for focused attention; 2) we use the generalized intersection box prediction task to effectively guide our model to focus on occlusion-specific regions; 3) our model achieves a new state-of-the-art performance on distance-aware relationship detection. Specifically, our model increases the distance F1-score from 33.8% to 38.6% and boosts the occlusion F1-score from 34.4% to 41.2%. Our code and data will be publicly available.

C-band 200 Gbit/s/λ PAM-4 transmission over 2-km SSMF using look-up-table pre-distortion combined with nonlinear Tomlinson-Harashima pre-coding.

The performance of high baud-rate intensity modulation direct detection (IM-DD) transmissions is severely degraded by both the linear and nonlinear inter-symbol interference (ISI). Here, we propose and experimentally demonstrate a transmitter-side look-up-table pre-distortion combined with nonlinear Tomlinson-Harashima pre-coding (LUT_PD-NTHP) scheme with the capability of mitigating the linear and nonlinear ISI simultaneously, enabling a C-band 200 Gbit/s/λ PAM-4 transmission over 2-km standard single mode fiber (SSMF), under an end-to-end 10-dB bandwidth of about 20 GHz. The proposed LUT_PD-NTHP scheme is experimentally verified to be superior to the LUT pre-distortion combined with linear THP (LUT_PD-LTHP) scheme, in terms of both the receiver sensitivity and the LUT storage requirement, when only the feed-forward equalization (FFE) is used at the receiver-side. In particular, after the 200 Gbit/s PAM-4 signal transmission over the 2-km SSMF without the chromatic dispersion (CD) compensation, the proposed LUT_PD-NTHP scheme with a LUT pattern length of 3 possesses not only 0.25 dB improvement of the receiver sensitivity but also about 99% LUT pattern reduction, in comparison with the LUT_PD-LTHP scheme with a LUT pattern length of 5.

Measurement of the sound velocity of shock compressed water.

The sound velocities of water in the Hugoniot states are investigated by laser shock compression of precompressed water in a diamond anvil cell. The obtained sound velocities in the off-Hugoniot region of liquid water at precompressed conditions are used to test the predictions of quantum molecular dynamics (QMD) simulations and the SESAME equation-of-state (EOS) library. It is found that the prediction of QMD simulations agrees with the experimental data while the prediction of SESAME EOS library underestimates the sound velocities probably due to its improper accounting for the ionization processes.

Regulation of c-Fos gene expression by NF-κB: a p65 homodimer binding site in mouse embryonic fibroblasts but not human HEK293 cells.

The immediate early gene c-Fos is reported to be regulated by Elk-1 and cAMP response element-binding protein (CREB), but whether nuclear factor (NF)-κB is also required for controlling c-Fos expression is unclear. In this study, we determined how NF-κB's coordination with Elk/serum response factor (SRF) regulates c-fos transcription. We report that PMA strongly induced c-Fos expression, but tumor necrosis factor (TNF)-α did not. In mouse embryonic fibroblasts, the PMA induction of c-Fos was suppressed by a deficiency in IKKα, IKKß, IKKγ, or p65. By contrast, in human embryonic kidney 293 cells, PMA induced c-Fos independently of p65. In accordance with these results, we identified an NF-κB binding site in the mouse but not human c-fos promoter. Under PMA stimulation, IKKα/ß mediated p65 phosphorylation and the binding of the p65 homodimer to the NF-κB site in the mouse c-fos promoter. Furthermore, our studies demonstrated independent but coordinated functions of the IKKα/ß-p65 and extracellular signal-regulated kinase (ERK)-Elk-1 pathways in the PMA induction of c-Fos. Collectively, these results reveal the distinct requirement of NF-κB for mouse and human c-fos regulation. Binding of the p65 homodimer to the κB site was indispensable for mouse c-fos expression, whereas the κB binding site was not present in the human c-fos promoter. Because of an inability to evoke sufficient ERK activation and Elk-1 phosphorylation, TNF-α induces c-Fos more weakly than PMA does in both mouse and human cells.