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Objective Non-steroidal anti-inflammatory drugs are used as first-line treatment of primary dysmenorrhea, but there has been no optimal clinical choice among non-steroidal anti-inflammatory drugs yet. The present study was to assess the relative benefits of different common non-steroidal anti-inflammatory drugs for primary dysmenorrhea patients with a network meta-analysis. Methods Randomized controlled trials were screened by our criteria and included in the network meta-analysis. Pain relief was considered as primary outcomes and adverse effect was supplied as a safety outcome, while additional rescue, assessment score, and pain intensity difference were secondary outcomes. All the indexes were evaluated with odds ratio or standardized mean difference. Surface under cumulative ranking curve result was used to calculate the ranking of each treatment. Results Totally, 72 randomized controlled trials of 5723 patients and 13 drugs were included in our study after screening. As for pain relief, all drugs except nimesulide, rofecoxib, and waldecoxib were superior to aspirin (odds ratio with 95% credible intervals, diclofenac: 0.28 (0.08, 0.86), flurbiprofen: 0.10 (0.03, 0.29), ibuprofen: 0.32 (0.14, 0.73), indomethacin: 0.21 (0.07, 0.58), ketoprofen: 0.25 (0.10, 0.64), mefenamic acid: 0.28 (0.09, 0.87), naproxen: 0.31 (0.15, 0.64), piroxicam: 0.15 (0.03, 0.59), and tiaprofenic acid: 0.17 (0.04, 0.63)). Aspirin also required additional rescue when compared with the majority of other drugs (flurbiprofen: 3.46 (1.15, 11.25), ibuprofen: 6.30 (2.08, 20.09), mefenamic acid: 7.32 (1.51, 37.71), naproxen: 2.66 (1.17, 6.55), and tiaprofenic acid: 9.58 (1.43, 94.63)). As for assessment of the whole treatment, ketoprofen, naproxen, rofecoxib, and ibuprofen got higher score significantly than placebo. In addition, ibuprofen performed better than placebo in pain intensity difference. Considering the safety, tiaprofenic acid and mefenamic acid were noticeable in low risk, and indomethacin revealed higher risk than any other drugs. According to the results of network analysis and surface under cumulative ranking curve, flurbiprofen was considered to be the best one among all the treatments in efficacy, and aspirin was worse than most of others. On the other hand, tiaprofenic acid and mefenamic acid were indicated as the safest drugs. Conclusion Considering the efficacy and safety, we recommended flurbiprofen and tiaprofenic acid as the optimal treatments for primary dysmenorrhea.

A novel copper-based metal-organic framework (Cu-MOF) with a large specific surface area and high porosity was synthesized. The Cu-MOF was a good peroxidase-mimicking enzyme and showed a high affinity with hydrogen peroxide in a wide pH range. The catalytic mechanism of Cu-MOF has been studied further based on comparing the characteristic of the Cu-MOF with some isomorphic MOFs. The catalytic activity center of Cu-MOF was determined to be the cupric ion rather than the ligand, which effectively promoted the generation of free radicals and electron transfer in the reaction progress. The high affinity of Cu-MOF to hydrogen peroxide proved it as an ideal catalyst for the chemiluminescence (CL) reaction involving hydrogen peroxide. Therefore, the CL method with high sensitivity could be established for detecting various substrates. A double-enzyme CL glucose biosensing platform was constructed for the determination of serum glucose employing the peroxidase-mimicking properties of Cu-MOF as well as glucose oxidase (GOx).

Synaptic vesicles (SVs) can be pooled across multiple synapses, prompting questions about their dynamic allocation for neurotransmission and plasticity. We find that the axonal traffic of recycling vesicles is not supported by ubiquitous microtubule-based motility but relies on actin instead. Vesicles freed from synaptic clusters undergo ~1 µm bouts of active transport, initiated by nearby elongation of actin filaments. Long distance translocation arises when successive bouts of active transport were linked by periods of free diffusion. The availability of SVs for active transport can be promptly increased by protein kinase A, a key player in neuromodulation. Vesicle motion is in turn impeded by shutting off axonal actin polymerization, mediated by nitric oxide-cyclic GMP signaling leading to inhibition of RhoA. These findings provide a potential framework for coordinating post-and pre-synaptic strength, using retrograde regulation of axonal actin dynamics to mobilize and recruit presynaptic SV resources. Transport of membrane proteins within the cell is thought to mainly rely on microtubule-based transport, but the role of microtubules in neuronal cell recycling of synaptic vesicles is unclear. Here, the authors show that axonal movement of recycling vesicles may be driven not by microtubules but primarily by actin polymerization.

This study aimed to assess temporal trends, health inequities and potential improvements in the burden of head and neck cancer (HNC) in middle-aged and older adults between 1990 and 2021, focusing on three major subtypes: larynx, nasopharynx, and lip/oral cavity cancers. A secondary analysis of the Global Burden of Disease Study (GBD) 2021 was performed, using age-standardised incidence rates (ASIR) and age-standardised disability-adjusted life years (ASDR) to quantify the burden of HNC. The average annual percent change was calculated to analyzed trends. The slope index of inequality (SII) and the concentration index quantified health inequities. Frontier analysis identified regions with potential for improvement. In 2021, there were approximately 650,205 new cases of overall HNC globally, resulting in 9,621,610 DALYs, with ASIR and ASDR both declining since 1990. ASIR exhibited a decrease for laryngeal and nasopharyngeal cancers, in contrast to an increase for lip and oral cavity cancers. ASDR decreased across all cancer types. The SII showed a notable shift in ASDR from countries with higher socio-demographic indices (SDI) in 1990 to those with lower SDI countries by 2021. Meantime, the concentration index revealed a worsening inequality in lower SDI countries. Frontier analyses across 204 countries and territories indicated that certain high SDI countries could effectively reduce ASDR for HNCs. The global burden of HNCs shown considerable regional disparities. Health inequalities have persisted, with lower SDI regions bearing a heavier burden, particularly in laryngeal and lip/oral cavity cancers. Developing tailored national cancer control plans and enhancing international medical cooperation are essential to reduce HNC burden and promote equitable health outcomes.

Volitional eye closure is observed only in conscious and awake humans, and is rare in animals. It is believed that eye closure can focus one's attention inward and facilitate activities such as meditation and mental imagery. Congenital blind individuals are also required to close their eyes for these activities. Resting-state functional magnetic resonance imaging (RS-fMRI) studies have found robust differences between the eyes-closed (EC) and eyes-open (EO) conditions in some brain regions in the sighted. This study analyzed data from 21 congenital blind individuals and 21 sighted controls by using amplitude of low-frequency fluctuation (ALFF) of RS-fMRI. The blind group and the sighted group shared similar pattern of differences between the EC and EO condition: ALFF was higher in the EC condition than the EO condition in the bilateral primary sensorimotor cortex, bilateral supplementary motor area, and inferior occipital cortex, while ALFF was lower in the EC condition than the EO condition in the medial prefrontal cortex, highlighting the “nature” effect on the difference between the EC and EO conditions. The results of other matrices such as fractional ALFF (fALFF) and regional homogeneity (ReHo) showed similar patterns to that of ALFF. Moreover, no significant difference was observed between the EC-EO pattern of the two subgroups of congenital blind (i.e., with and without light perception), suggesting that the EC-EO difference is irrespective of residual light perception which reinforced the “nature” effect. We also found between-group differences, i.e., more probably “nurture effect”, in the posterior insula and fusiform. Our results suggest that the acts of closing and opening the eyes are of importance for the congenital blind, and that these actions and their differences might be inherent in the nature of humans.

Janus particles, which have an attractive patch on the otherwise repulsive surface, have been commonly employed for anisotropic colloidal assembly. While current methods of particle synthesis allow for control over the patch size, they are generally limited to producing dome-shaped patches with a high symmetry (C ∞ ). Here, we report on the synthesis of Janus particles with patches of various tunable shapes, having reduced symmetries ranging from C 2v to C 3v and C 4v . The Janus particles are synthesized by partial encapsulation of an octahedral metal-organic framework particle (UiO-66) in a polymer matrix. The extent of encapsulation is precisely regulated by a stepwise, asymmetric dewetting process that exposes selected facets of the UiO-66 particle. With depletion interaction, the Janus particles spontaneously assemble into colloidal clusters reflecting the particles’ shapes and patch symmetries. We observe the formation of chiral structures, whereby chirality emerges from achiral building blocks. With the ability to encode symmetry and directional bonding information, our strategy could give access to more complex colloidal superstructures through assembly. Janus particles commonly exhibit a high-symmetry patch, constraining the range of possible assemblies. Here, the authors devise a synthetic approach to fine-tune the patch symmetry in Janus particles and showcase the assembly of these particles into chiral colloidal clusters.

Urban delivery, especially the last-mile delivery, has become an increasingly important area in the global supply chain along with the boom of e-commerce. Delivery companies and merchants can introduce some innovative solutions such as the equipment of autonomous vehicles (AVs) to decrease their operating costs, environmental impact, and social risks during the delivery process. This paper mainly develops a mathematical model to get the best allocation of AVs among city logistics centers (CLCs) as a mixed delivery method. The advantage of the presented model stems from considering the equipment cost, the delivery cost, and the CO2 emission, which is measured through social carbon cost (SCC). In addition, this paper establishes a risk model considering the impact of seasonal variations to evaluate the infection risk of delivery during pandemic periods for four potential delivery scenarios: customers going to CLCs, ordering online and picking-up at CLCs, delivering by traditional vehicles (TVs), and delivering by the mixed method with the optimal allocation of AVs. The research finds the optimal allocation for a London case, reveals the relationship between the nominal service capacity (NCpa) of CLCs and the optimal number of CLCs equipped with AVs, concludes that the more CLCs are equipped with AVs, the fewer CO2 emissions and the fewer citizens will be infected, and provides some managerial insights that may help delivery companies and merchants make appropriate decisions about the allocation of AVs.

Asia bears a disproportionate burden of head and neck cancer (HNC). This study aimed to analyze its spatial distribution and temporal trends in Asia from 1990 to 2021, projecting trends to 2030. We performed a secondary analysis of data from the Global Burden of Disease Study (GBD) 2021, examining disability-adjusted life years (DALYs) for HNC and its five major subtypes: nasopharyngeal cancer (NPC), thyroid cancer (TC), laryngeal cancer (LC), lip and oral cavity cancer (LOC), and other pharyngeal cancer (OPC), across five Asian subregions and 34 countries/territories from 1990 to 2021. Temporal trends were evaluated using Joinpoint regression, and projections to 2030 were generated through Bayesian Age-Period-Cohort model. From 1990 to 2021, DALYs for HNC increased in five subregions. In contrast, age-standardized DALY rates (ASDR) declined across all subregions except South Asia, with East Asia experiencing the most rapid decrease. In 2021, South Asia recorded the highest DALYs (6,412,639) and ASDR (405.82 per 100,000) for HNC. LOC was the main HNC type in most regions (32.41% - 46.23%), except East Asia, where NPC was most common (38.96%). South Asia also exhibited the highest ASDRs for LC (67.29), LOC (182.29), and OPC (93.00) per 100,000, while Southeast Asia demonstrated the highest ASDRs for NPC (50.77) and TC (18.22) per 100,000. Significant disparities in ASDR trends for HNC subtypes were observed across Asia. By 2030, South Asia is projected to maintain the highest ASDRs for HNC (394.59), LC (62.98), LOC (185.31), and OPC (95.50). East and Southeast Asia are expected to show comparable ASDRs for NPC (approximately 50.00), with Southeast Asia leading in TC ASDR (23.90). HNC remains a significant public health challenge in Asia, with substantial heterogeneity in its subtypes across the five subregions. Implementing targeted, region-specific strategies is crucial to mitigating the disease burden.

Summary In Arabidopsis, the initiation and proliferation of stomatal lineage cells is controlled by SPEECHLESS (SPCH). Phosphorylation of SPCH at the post‐translational level has been reported to regulate stomatal development. Here we report that IDD16 acts as a negative regulator for stomatal initiation by directly regulating SPCH transcription. In Arabidopsis, IDD16 overexpression decreased abaxial stomatal density in a dose‐dependent manner. Time course analysis revealed that the initiation of stomatal precursor cells in the IDD16‐OE plants was severely inhibited. Consistent with these findings, the transcription of SPCH was greatly repressed in the IDD16‐OE plants. In contrast, IDD16‐RNAi transgenic line resulted in enhanced stomatal density, suggesting that IDD16 is an intrinsic regulator of stomatal development. ChIP analysis indicated that IDD16 could directly bind to the SPCH promoter. Furthermore, Arabidopsis plants overexpressing IDD16 exhibited significantly increased drought tolerance and higher integrated water use efficiency (WUE) due to reduction in leaf transpiration. Collectively, our results established that IDD16 negatively regulates stomatal initiation via trans‐repression of SPCH, and thus provide a practical tool for increasing plant WUE through the manipulation of IDD16 expression.

Background Human responses and acclimation to the environmental stresses of high altitude and low oxygen are multifaceted and regulated by multiple genes. However, the mechanism of how the body adjusts in a low-oxygen environment is not yet clear. Results Hence, we performed RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) to observe the changes of transcriptome and chromatin accessibility in the peripheral blood of eight individuals at 1 h post adaptation in a simulated plateau environment with 3500 m and 4500 m altitude, respectively. Differential expression analysis and the Boruta algorithm identified differentially expressed genes (DEGs) and differentially accessible regions (DARs) associated with hypoxia adaptation. Specifically, RNA-seq identified 93 and 7 DEGs after 1 h post adaptation with 3500 m altitude and 45 and 8 DEGs after 1 h adaptation with 4500 m. Additionally, ATAC-seq screened 12 and 4 DARs in 3500 m altitude adaption and 15 and 5 DARs in 4500 m altitude adaption. Moreover, the combined analysis of RNA-seq and ATAC-seq revealed that 10 hub genes were independently identified from the protein–protein interaction (PPI) network for each altitude. Gene enrichment analysis displayed that most hub genes were related with hypoxia pathways. Conclusions Our results can provide the reference for the early response of the organism to hypoxic adaptation.