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Background: Cancer incidence and mortality have been increasing, and cancer is still the leading cause of death all over the world. Therefore, expanding the arsenal of anticancer drugs with high efficiency and low toxicity is still one of the most challenging tasks. As a branch of antitumor drug design and discovery, dual-targeting drug candidates draw extensive attention. Objective:: In this work, we try to construct a multitarget drug candidate and evaluate its antitumor effects. Methods: Hsp90 and histone deacetylase were selected as two targets to design a dual targeting inhibitor w11. Enzyme inhibition work, cell viability assay, and docking simulation were carried out to evaluate the activity of the compound. Results: w11 could inhibit the activity of Hsp90α and HDAC6 with the IC50 of 50.1 nM and 8.1 nM, respectively. In cell viability assay, five human tumor cell lines Eca-109, FaDu, HN6, MCF-7 and MDAMB- 231 were used, results showed that w11 could potently inhibit the proliferation of three human lines with IC50 values in the nM range. Molecular docking experiments proved the rationality of structure design. Conclusion: Compound w11 was a potent Hsp90 and HDAC dual inhibitor for anticancer research.

Aged cells have declined regenerative ability when subjected to environmental insult. Here we elucidate the mechanism by which mechanical stimulus induces hair regeneration at the microenvironmental regulation level using the hair plucking and organoid culture models. We observed that the skin cells harvested from post-plucking day 3 (PPD3) have the best self-organizing ability during skin organoid culture and have the highest hair regeneration upon transplantation. By bulk RNA sequencing (RNA-seq) and single-cell RNA-seq analysis and in situ hybridization, we identified that the chemokine signaling pathway genes including CCL2 are significantly increased in the skin at PPD3 and in skin organoid cultures. Immunostaining shows that the PPD3 skin epithelial cells have increased multipotency, which is verified by the ability to self-organize to form epidermal aggregates during organoid culture. By adding CCL2 recombinant protein to the organoid culture using an environmental reprogramming protocol, we observed the PPD0 adult skin cells, which lose their regenerative ability can self-organize in organoid culture and regenerate hair follicles robustly upon transplantation. Our study demonstrates that CCL2 functions in immune regulation of hair regeneration under mechanical stimulus, and enhances cell multipotency during organoid culture. This provides a therapeutic potential for future clinical application.

In a coil magnetometer, the size and uniformity of the bias magnetic field generated by the Helmholtz coil directly determine the accuracy of the solution of the geomagnetic direction. The design of traditional spherical coils relies heavily on the manual experience or mathematical derivation, making it difficult to obtain optimal parameters or requiring larger spherical coils. To address the problem, first, a coaxial symmetrical spherical coil model that improves space utilization was established. Second, an optimal design method for the spherical magnetic field generation coil based on a differential evolution algorithm was proposed. Third, the optimal bias magnetic field was obtained without increasing the volume of the coil. The verification results showed that the magnetic non-uniformity and magnetic gradient of the bias field generated by the optimized coil were reduced by 63.2% and 82.8%, respectively.

Secondary organic aerosol (SOA) has been identified as a major contributor to fine particulate matter (PM2.5) in the North China Plain (NCP). However, the chemical mechanisms involved are still unclear due to incomplete understanding of its multiple formation processes. Here we report field observations in summer in Handan of the NCP, based on high-resolution online measurements. Our results reveal the formation of SOA via photochemistry and two types of aqueous-phase chemistry, the latter of which include nocturnal and daytime processing. The photochemical pathway is the most important under high-Ox (i.e., O3 + NO2) conditions (65.1 ± 20.4 ppb). The efficient SOA formation from photochemistry (Ox-initiated SOA) dominated the daytime (65 % to OA), with an average growth rate of 0.8 µgm-3h-1. During the high-relative-humidity (RH; 83.7 ± 12.5 %) period, strong nocturnal aqueous-phase SOA formation (aqSOA) played a significant role in SOA production (45 % to OA), with a nighttime growth rate of 0.6 µgm-3h-1. Meanwhile, an equally fast growth rate of 0.6 µgm-3h-1 of Ox-initiated SOA from daytime aqueous-phase photochemistry was also observed, which contributed 39 % to OA, showing that photochemistry in the aqueous phase is also a non-negligible pathway in summer. The primary-related SOA (SOA attributed to primary particulate organics) and aqSOA are related to residential coal combustion activities, supported by distinct fragments from polycyclic aromatic hydrocarbons (PAHs). Moreover, the conversion and rapid oxidation of primary-related SOA to aqSOA were possible in the aqueous phase under high-RH conditions. This work sheds light on the multiple formation pathways of SOA in ambient air of complex pollution and improves our understanding of ambient SOA formation and aging in summer with high oxidation capacity.

Since the industrial revolution, global carbon emissions have continued to increase, and after entering the 21st century, the trend of global warming has become more and more obvious. This paper first use the collected 10-year monthly average temperature data and divide them into two groups: 2012.3~2022.2 and 2022.3~2022.10, then conduct the Mann-Whitney U test, and find that the temperature increase in March 2022 did not increase significantly; then we three models are established to predict the future global temperature, the first model is ARIMA, the second model is BP neural network, and the third model is GA-BP neural network. Three models are used to predict the time when the future temperature will reach 20°C, ARIMA predicts the time is 2050, BP is 2046, and GA-BP is 2045. Finally, this paper use MAE, MAPE, and RMSE to evaluate the accuracy of the model, and find that GA-BP has the highest accuracy, followed by BP, and ARIMA is the worst.

This correspondence investigates a reconfigurable intelligent surface (RIS)-assisted wireless communication system with security threats. The RIS is deployed to enhance the secrecy outage probability (SOP) of the data sent to a legitimate user. By deriving the distributions of the received signal-to-noise-ratios (SNRs) at the legitimate user and the eavesdropper, we formulate, in a closed-form expression, a tight bound for the SOP under the constraint of discrete phase control at the RIS. The SOP is characterized as a function of the number of antenna elements, $N$, and the number of discrete phase choices, $2^b$. It is revealed that the performance loss in terms of SOP due to the discrete phase control is ignorable for large $N$ when $b\!\geq\!3$. In addition, we explicitly quantify this SOP loss when binary phase shifts with $b\!=\!1$ is utilized. It is identified that increasing the RIS antenna elements by $1.6$ times can achieve the same SOP with binary phase shifts as that by the RIS with ideally continuous phase shifts. Numerical simulations are conducted to verify the accuracy of these theoretical observations., Accepted by IEEE Transactions on Vehicular Technology

Internet-of-Everything (IoE) has gradually been recognized as an integral part of future wireless networks. In IoE, there can be an ultra-massive number of smart devices of various types to be served, imposing multi-dimensional requirements on wireless communication, sensing, and security. In this article, we provide a tutorial overview of the promising intelligent reflection communication (IRC) technologies, including reconfigurable intelligent surface (RIS) and ambient backscatter communication (AmBC), to support the requirements of IoE applications beyond the fifth-generation (5G) wireless communication network. Specifically, we elaborate on the benefits of IRC-assisted IoE in the context of the space-air-ground integrated communications and green communications, which are regarded as key features of supporting future IoE application from society and industries. Furthermore, we envision that the IRC-assisted communication and sensing can mutually benefit each other and articulate multiple ways of enhancing the security in IoE by the IRC. Numerical results help illustrate the importance of the IRC in unfavorable secrecy environments. Finally, open research issues and challenges about the IRC-assisted IoE are presented., Accepted by IEEE Wireless Communications

We aimed to investigate the surgical techniques, efficacy, and safety of Starr frame-assisted and minimally invasive internal fixation for simultaneous anterior and posterior ring stability in pelvic fractures.The clinical data of 22 patients with anterior and posterior pelvic ring injuries who underwent Starr frame-assisted and minimally invasive internal fixation were retrospectively collected. The anterior pelvic ring was fixed with an anterior subcutaneous internal fixator (INFIX), and the posterior pelvic ring was fixed with sacroiliac screws. The operative time, intraoperative blood loss, fluoroscopy times, number of assistants, complications, and weight-bearing time were analyzed. The Matta score was used to evaluate the fracture reduction. The Majeed score was used to evaluate clinical efficacy, and Gibbon's classification was used to estimate the occurrence of sacral nerve injury.All 22 patients were treated with sacroiliac screws for posterior ring injuries, including 12 cases with single sacroiliac screws, nine with two sacroiliac screws, and one with three sacroiliac screws. INFIX was used for all anterior ring fixation, including two screws in seven cases, three screws in 13 cases, and four screws in two cases. The fracture reduction quality was excellent in 15 cases, good in four cases, and moderate in three cases by Matta scores. All patients were followed up for 6-20 (12.5 ± 5.7) months. Callus-formation time based on postoperative X-ray was 3-8 (4.3 ± 1.2) weeks. Weight-bearing time was 3-12 (6.3 ± 2.8) weeks after surgery. At the last follow-up, 15 patients were evaluated as excellent, five as good, and two as fair according to the Majeed score. Gibbons' classification showed that one of the three patients with sacral nerve injury recovered completely and two did not recover. Complications occurred in six patients, including one with internal fixation loosening, two with anterolateral thigh paresthesia, one with malunion, one with nonunion, and one with heterotopic ossification.Starr frame-assisted and minimally invasive internal fixation could stabilize the anterior and posterior pelvic rings simultaneously, overcoming the difficulty of fracture reduction. This technique can help patients with early postoperative weight-bearing and improved functional outcomes, providing a novel modality for the minimally invasive treatment of pelvic ring injuries.

A mechanical flocculation system with multi-chambers in series is commonly used as the advanced phosphorus removal technology for wastewater treatment. This work aims to numerically investigate the inner states and overall performance of industrial-scale mechanical flocculators in series. This is based on our previously developed computational fluid dynamics (CFD) flocculation model which is extended to consider the key chemical reactions of phosphorus removal. The effects of the number of flocculation chambers, locations, and sizes of the flocculation chamber connection as well as operational combinations of impeller speeds are investigated. With a decreasing number of flocculation chambers, the main vortexes and chemical reactions are weakened, while the small flocs form. Both the phosphorus removal efficiency η and the average floc size dp reduce as the number of flocculation chambers decreases. The connection location of flocculation chambers directly determines the turbulent flow, thus influencing the key performance indicators. However, the phosphorus removal efficiency η and average particle size dp are little affected by the size of the flocculation chamber connection. As the impeller speeds in series gradually increase, the gradient of floc size distribution in each chamber is enlarged and the chemical reaction is enhanced over the working volume.