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Abstract Pronounced spatial disparities in heatwave trends are bound up with a diversity of atmospheric signals with complex variations, including different phases and wavenumbers. However, assessing their relationships quantitatively remains a challenging problem. Here, we use a network-searching approach to identify the strengths of heatwave-related atmospheric teleconnections (AT) with ERA5 reanalysis data. This way, we quantify the close links between heatwave intensity and AT in the Northern Hemisphere. Approximately half of the interannual variability of heatwaves is explained and nearly 80% of the zonally asymmetric trend signs are estimated correctly by the AT changes in the mid-latitudes. We also uncover that the likelihood of extremely hot summers has increased sharply by a factor of 4.5 after 2000 over areas with enhanced AT, but remained almost unchanged over the areas with attenuated AT. Furthermore, reproducing Eastern European heatwave trends among various models of the Coupled Model Intercomparison Project Phase 6 largely depends on the simulated Eurasian AT changes, highlighting the potentially significant impact of AT shifts on the simulation and projection of heatwaves.

Abstract The comprehensive understanding of propagation patterns of extreme precipitation events (EPEs) is essential for early warning of associated hazards such as floods and landslides. In this study, we utilize climate networks based on an event synchronization measure to investigate the propagation patterns of EPEs over the global land masses, and identify 16 major propagation pathways. We explain them in association with regional weather systems, topographic effects, and travelling Rossby wave patterns. We also demonstrate that the revealed propagation pathways carry substantial EPE predictability in certain areas, such as in the Appalachian, the Andes mountains. Our results help to improve the understanding of key propagation patterns of EPEs, where the global diversity of the propagated patterns of EPEs and corresponding potential predictability provide prior knowledge for predicting EPEs, and demonstrate the power of climate network approaches to study the spatiotemporal connectivity of extreme events in the climate system.

Abstract Osteoarthritis is a degenerative joint disease with joint pain as the main symptom, caused by fibrosis and loss of articular cartilage. Due to the complexity and heterogeneity of osteoarthritis, there is a lack of effective individualized disease-modifying osteoarthritis drugs in clinical practice. Chondrocyte senescence is reported to participate in occurrence and progression of osteoarthritis. Here we show that small molecule 10-hydroxy-2-decenoic acid suppresses cartilage degeneration and relieves pain in the chondrocytes, cartilage explants from osteoarthritis patients, surgery-induced medial meniscus destabilization or naturally aged male mice. We further confirm that 10-hydroxy-2-decenoic acid exerts a protective effect by targeting the glycosylation site in the Asp_Arg_Hydrox domain of aspartyl β-hydroxylase. Mechanistically, 10-hydroxy-2-decenoic acid alleviate cellular senescence through the ERK/p53/p21 and GSK3β/p16 pathways in the chondrocytes. Our study uncovers that 10-hydroxy-2-decenoic acid modulate cartilage metabolism by targeting aspartyl β-hydroxylase to inhibit chondrocyte senescence in osteoarthritis. 10-hydroxy-2-decenoic acid may be a promising therapeutic drug against osteoarthritis.

Abstract To compare the clinical efficacy of interlaminar endoscopic surgical system delta (iLESSYS-Delta) discectomy with that of classical fenestration discectomy for treating lumbar disc herniation. Patients who underwent iLESSYS-Delta or fenestration discectomy were enrolled in this study. Baseline information and clinical indicators were collected. The baseline data were matched using propensity score matching. Fifty-two patients were in each group. In the iLESSYS-Delta cohort, the volume of intraoperative bleeding was 18.17 ± 4.20 ml, the length of postoperative hospital stay was 4.16 ± 2.29 days, and the length of postoperative off-bed activity was 1.58 ± 0.88 days. In contrast, in the fenestration group, the volume of intraoperative bleeding was 32.50 ± 17.13 ml, the length of postoperative hospital stay was 6.66 ± 2.44 days, and the length of postoperative off-bed activity was 3.18 ± 1.28 days. The difference between the two groups was statistically significant (P 0.05). The two groups showed no significant differences in clinical effects, postoperative recurrence rates, or perioperative complications. iLESSYS-Delta can cause less intraoperative bleeding and faster recovery than fenestration discectomy.

Abstract Microbot collectives can cooperate to accomplish complex tasks that are difficult for a single individual. However, various force-induced microbot collectives maintained by weak magnetic, light, and electric fields still face challenges such as unstable connections, the need for a continuous external stimuli source, and imprecise individual control. Here, we construct magnetic and light-driven ant microbot collectives capable of reconfiguring multiple assembled architectures with robustness. This methodology utilizes a flexible two-photon polymerization strategy to fabricate microbots consisting of magnetic photoresist, hydrogel, and metal nanoparticles. Under the cooperation of magnetic and light fields, the microbots can reversibly and selectively assemble (e.g., 90° assembly and 180° assembly) into various morphologies. Moreover, we demonstrate the ability of assembled microbots to cross a one-body-length gap and their adaptive capability to move through a constriction and transport microcargo. Our strategy will broaden the abilities of clustered microbots, including gap traversal, micro-object manipulation, and drug delivery.

Abstract This study aimed to analyze the impact of the lockdown period due to COVID-19 pandemic on the mental health status of healthcare workers and identify the related risk factors of psychosomatic distress. We conducted an online questionnaire survey to investigate the general demographic characteristics, perceived stress level, adult attachment style (AAS), family cohesion and adaptability, social support, sleep state, emotional state, and physical health of healthcare workers during the lockdown period due to the pandemic in 2022. We compared the mental health status between doctors and nurses, and further analyzed the factors influencing sleep, emotions, physical symptoms, and severe psychosomatic distress separately. For factors that showed statistical significance in the univariate analysis, forward stepwise regression was used for logistic regression analysis to identify risk factors for the corresponding issues. A total of 622 healthcare workers participated in the survey. Among the participants, 121 (19.5%) reported sleep problems, 209 (33.6%) had negative emotional states, and 147 (23.6%) reported physical health problems. There were 48 (7.7%) healthcare workers with severe psychosomatic distress. Compared to the group of nurses, the group of doctors exhibit a higher prevalence of emotional issues, physical health problems and psychosomatic distress. Perceived stress was identified as a risk factor for sleep disturbance, while living with others during quarantine and family adaptability were identified as protective factors. Higher educational background and perceived stress were identified as risk factors for negative emotion, while subjective support was identified as a protective factor. Perceived stress and coming from a rural area were also identified as risk factors for physical health. Overall, for the comparison between the no psychosomatic distress and severe psychosomatic distress groups, perceived stress was identified as a risk factor for severe psychosomatic distress, while subjective support was identified as a protective factor. Healthcare workers’ potential mental and physical health problems are related to their educational background, family cohesion and adaptability, perceived stress and social support. This makes it clearer on how to deal with and prevent adverse consequences when facing stressful situations.

Abstract Osteoporosis is a systemic metabolic bone disorder for which inflammatory cytokines play an important role. To develop new osteoporosis treatments, strategies for improving the microenvironment for osteoblast and osteoclast balance are needed. Tumor necrosis factor-α (TNF-α) plays an important role in the initiation and development of osteoporosis. Atsttrin is an engineered protein derived from the growth factor, progranulin (PGRN). The present study investigates whether Atsttrin affects osteoclast formation and osteoblast formation. Here we show Atsttrin inhibits TNF-α-induced osteoclastogenesis and inflammation. Further mechanistic investigation indicates Atsttrin inhibits TNF-α-induced osteoclastogenesis through the TNFR1 signaling pathway. Moreover, Atsttrin rescues TNF-α-mediated inhibition of osteoblastogenesis via the TNFR1 pathway. Importantly, the present study indicates that while Atsttrin cannot directly induce osteoblastogenesis, it can significantly enhance osteoblastogenesis through TNFR2-Akt-Erk1/2 signaling. These results suggest that Atsttrin treatment could potentially be a strategy for maintaining proper bone homeostasis by regulating the osteoclast/osteoblast balance. Additionally, these results provide new insights for other bone metabolism-related diseases.

Abstract The efficacy of aminolevulinic acid (5-ALA)-based photodynamic diagnosis (5-ALA-PDD) and photodynamic therapy (5-ALA-PDT) is dependent on 5-ALA-induced cancer-specific accumulation of protoporphyrin IX (PpIX). We previously reported that inhibition of oncogenic Ras/MEK increases PpIX accumulation in cancer cells by reducing PpIX efflux through ATP-binding cassette sub-family B member 1 (ABCB1) and ferrochelatase (FECH)-catalysed PpIX conversion to haem. Here, we sought to identify the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation via ABCB1 and FECH. First, we demonstrated that Ras/MEK activation reduced PpIX accumulation in RasV12-transformed NIH3T3 cells and HRAS transgenic mice. Knockdown of p90 ribosomal S6 kinases (RSK) 2, 3, or 4 increased PpIX accumulation in RasV12-transformed NIH3T3 cells. Further, treatment with an RSK inhibitor reduced ABCB1 expression and increased PpIX accumulation. Moreover, HIF-1α expression was reduced when RasV12-transformed NIH3T3 cells were treated with a MEK inhibitor, demonstrating that HIF-1α is a downstream element of MEK. HIF-1α inhibition decreased FECH activity and increased PpIX accumulation. Finally, we demonstrated the involvement of RSKs and HIF-1α in the regulation of PpIX accumulation in human cancer cell lines. These results demonstrate that the RSK-ABCB1 and HIF-1α-FECH axes are the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation.