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As a model for delivering infrastructure initiatives, public–private partnerships (PPPs) have gained significant popularity in recent years. The globalization of PPP has exposed them to elevated risks emanating from the international real economy and financial market, which can ultimately result in project cancellations or distress. This study analyzes risk factors affecting the sustainable outcomes of global PPP projects from a stakeholder perspective. After identifying the interests of key stakeholders and examining how various risks influence stakeholders’ interests, a two-step binomial probit model is used to investigate domestic and international risk factors in PPP arrangements based on the World Bank PPI database. The empirical results indicate that inflation has a substantially positive effect on project failure, while factors such as PPP experience, central government involvement, exchange rate fluctuations, etc., significantly contribute to PPP success. In addition, the study demonstrates that trade openness and net foreign direct investment (FDI) inflow are crucial for the transmission of global risks. The study also provides policy implications and recommendations from a risk allocation–stakeholder relationship perspective to enhance the resilience of PPP initiatives based on these findings.

A multidimensional sleep health framework improves screening and treatment efficacy by simultaneously addressing multiple sleep domains. However, limited studies have used objective measures to evaluate the co-occurrence of diverse unhealthy sleep characteristics and their pleiotropic health effects. To represent real-world sleep patterns, we introduce the Unfavorable Sleep Profile (USP), an integrated multidimensional sleep health metric developed using accelerometer data in the UK Biobank ( N  = 85,233; aged 43–79 years). USP captures five domains: sleep timing, efficiency, duration, rhythmicity, and regularity. Phenome-wide association study found that USP was significantly associated with 76 out of 526 incident health outcomes over 7.9 years of follow-up. We identified several upstream environmental risk factors associated with USP, including low socioeconomic status. Whole-genome sequence analyses identified common variants in MEIS1 and rare coding variants in TTC1 associated with USP. We validated the USP framework in an independent cohort, the Multi-Ethnic Study of Atherosclerosis. Our findings underscore the importance of multidimensional sleep health assessment in predicting and potentially mitigating a wide array of health disorders and advance genetic insights into sleep health. Sleep health involves multiple interrelated domains, yet few studies have objectively evaluated their combined impact on long-term disease risk. Here, the authors show that an accelerometer-derived Unfavourable Sleep Profile (USP) predicts diverse health outcomes and reveals genetic and environmental contributions to poor sleep.

The branch predictor is widely used to enhance processor performance, but it also constitutes one of the major energy‐consuming components in processors. We found that approximately 32% of instruction blocks in a decoupled frontend do not contain branch instructions, while 30.8% of instruction blocks contain only conditional branches. However, because the type of instructions within a block cannot be determined during prediction, branch prediction must be executed every cycle. In this work, we propose the next block type (NBT) and no branch sequence table (NST) for predicting instruction block types. These mechanisms occupy minimal space and are straightforward to implement. For a four‐way out‐of‐order processor, the NBT and NST reduce the branch predictor’s energy consumption by 52.36% and processor’s energy consumption by 4.1% without sacrificing the processor’s instructions per cycle (IPC) and branch prediction accuracy.

Global change is accelerating the chemical weathering of silicate rocks and the associated phosphorus release. However, the effects of phosphorus release on the global patterns of plant phosphorus limitation remain unclear. Here, we show that approximately 47% of the exposed areas in global silicate rocks are subject to phosphorus limitation of vegetation growth, as estimated using the ratio of leaf nitrogen to phosphorus resorption efficiency. Phosphorus-limited areas are projected to expand markedly with global warming, and the proportion may reach 54 − 59% according to two model scenarios (the shared socioeconomic pathways SSP2-4.5 and SSP5-8.5). Nevertheless, phosphorus release from accelerated chemical weathering of silicate rocks mitigates this limitation, with a relative contribution of approximately 15.5%. This work highlights the implications of accelerated chemical weathering of silicate rocks and its resulting phosphorus release for the global patterns of phosphorus limitation, providing a scientific foundation for phosphorus management strategies. Climate warming is projected to expand plant phosphorus limitation from 47% to 59% of global silicate rock areas. However, phosphorus release from accelerated chemical weathering of these rocks offsets about 15.5% of this increase.

Programmed cell death is a suicidal defense mechanism for eukaryotes to combat pathogen infection. In the evolutionary arms race with the host, bacteria are endowed with ingenious tactics to block host cell death to facilitate their replication. Blocking host cell death is an important virulence strategy employed by many bacterial pathogens. We recently reported that Shigella flexneri inhibits host pyroptosis by delivering a type III secretion system (T3SS) effector OspC3 that catalyzes a novel arginine ADP-riboxanation modification on caspase-4/11. Here, we investigated the OspC3 homologue CopC from Chromobacterium violaceum , an opportunistic but sometimes deadly bacterial pathogen. CopC bears the same arginine ADP-riboxanase activity as OspC3, but with a different substrate specificity. Through proteomic analysis, we first identified host calmodulin (CaM) as a binding partner of CopC. The analyses additionally revealed that CopC preferably modifies apoptotic caspases including caspase-7, -8 and -9. This results in suppression of both extrinsic and intrinsic apoptosis programs in C. violaceum -infected cells. Biochemical reconstitution showed that CopC requires binding to CaM, specifically in the calcium-free state, to achieve efficient ADP-riboxanation of the caspases. We determined crystal structure of the CaM-CopC-CASP7 ternary complex, which illustrates the caspase recognition mechanism and a unique CaM-binding mode in CopC. Structure-directed mutagenesis validated the functional significance of CaM binding for stimulating CopC modification of its caspase substrates. CopC adopts an ADP-ribosyltransferase-like fold with a unique His-Phe-Glu catalytic triad, featuring two acidic residues critical for site-specific arginine ADP-riboxanation. Our study expands and deepens our understanding of the OspC family of ADP-riboxanase effectors. IMPORTANCE Programmed cell death is a suicidal defense mechanism for eukaryotes to combat pathogen infection. In the evolutionary arms race with the host, bacteria are endowed with ingenious tactics to block host cell death to facilitate their replication. Here, we report that the C. violaceum effector CopC ADP-riboxanates caspase-7/8/9, enabled by interacting with the host factor calmodulin, to block host cell apoptosis, illustrating a unique and sophisticated strategy adopted by the pathogen to counteract host defense.

This paper investigates the profile of COVID-19 cases in Hong Kong, highlighting the unique age structure of confirmed cases compared to other territories. While the majority of cases in most territories around the world have fitted an older age profile, our analysis shows that positive cases in Hong Kong have been concentrated among younger age groups, with the largest incidence of cases reported in the 15-24 age group. This is despite the population's rapidly aging structure and extremely high levels of population density. Using detailed case data from Hong Kong's Centre for Health Department and Immigration Department, we analyze the sex and age distribution of the confirmed cases along with their recent travel histories and immigration flows for the period January to April 2020. Our analysis highlights Hong Kong's high proportion of imported cases and large overseas student population in developing COVID-19 hotspot areas such as the United Kingdom. Combined with community action and targeted and aggressive early policy measures taken to contain the virus, these factors may have contributed to the uniquely younger age structure of COVID-19 cases in the city. Consequently, this young profile of confirmed cases may have prevented fatalities in the territory. Recent research has highlighted the importance of a demographic approach to understanding COVID-19 transmission and fatality rates. The experience in Hong Kong shows that while an older population age structure may be important for understanding COVID-19 fatality, it is not a given. From a social science perspective at least, there is 'no easy answer' to why one area should experience COVID-19 differently from another.

In this study, we employed the principle of Relative Mode Transfer Method (RMTM) to establish a model for a single pendulum subjected to sudden changes in its length. An experimental platform for image processing was constructed to accurately track the position of a moving ball, enabling experimental verification of the pendulum’s motion under specific operating conditions. The experimental data demonstrated excellent agreement with simulated numerical results, validating the effectiveness of the proposed methodology. Furthermore, we performed simulations of a double obstacle pendulum system, investigating the effects of different parameters, including obstacle pin positions, quantities, and initial release angles, on the pendulum’s motion through numerical simulations. This research provides novel insights into addressing the challenges associated with abrupt and continuous changes in pendulum length.

Nonlinear optics, which is a subject for studying the interaction between intense light and materials, has great impact on various research fields. Since many structures in biological tissues exhibit strong nonlinear optical effects, nonlinear optics has been widely applied in biomedical studies. Especially in the aspect of bio-imaging, nonlinear optical techniques can provide rapid, label-free and chemically specific imaging of biological samples, which enable the investigation of biological processes and analysis of samples beyond other microscopy techniques. In this review, we focus on the introduction of nonlinear optical processes and their applications in bio-imaging as well as the recent advances in this filed. Our perspective of this field is also presented.

Accumulating evidence indicates that exosomes help to regulate bone homeostasis. The roles of bone-derived exosomes have been well-described; however, recent studies have shown that some non-bone-derived exosomes have better bone targeting ability than bone-derived exosomes and that their performance as a drug delivery vehicle for regulating bone homeostasis may be better than that of bone-derived exosomes, and the sources of non-bone-derived exosomes are more extensive and can thus be better for clinical needs. Here, we sort non-bone-derived exosomes and describe their composition and biogenesis. Their roles and specific mechanisms in bone homeostasis and bone-related diseases are also discussed. Furthermore, we reveal obstacles to current research and future challenges in the practical application of exosomes, and we provide potential strategies for more effective application of exosomes for the regulation of bone homeostasis and the treatment of bone-related diseases. 67yBviMJcTRjcZnyRK6kR4 Video Abstract

Heart failure with preserved ejection fraction (HFpEF) is a major subtype of heart failure, primarily characterized by a normal or mildly reduced left ventricular ejection fraction along with left ventricular diastolic dysfunction. Recent studies have shown that the prevalence of HFpEF is higher in women than that in men, particularly in postmenopausal women. Concurrently, it has been observed that the incidence of risk factors contributing to HFpEF (such as obesity, hypertension, diabetes, and atrial fibrillation) also notably increases post-menopause, affecting the incidence of HFpEF. This review aimed to examine the relationship between estrogen and risk factors associated with HFpEF, clarifying the underlying mechanisms through which estrogen affects these risk factors from epidemiological and pathophysiological perspectives. This review also provides a comprehensive understanding of the association between estrogen and the risk factors for HFpEF, thus helping explore potential targets for HFpEF treatment.