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Chromosome instability (CIN) and subsequent aneuploidy are prevalent in various human malignancies, influencing tumor progression such as metastases and relapses. Extensive studies demonstrate the development of chemoresistance in high-CIN tumors, which poses significant therapeutic challenges. Given the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma (CRC), here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC cells. By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC. Subsequent analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these drugs. We further revealed the critical role of BCL-XL in the viability of high-CIN CRC cells. In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.

Birefringent crystals, which can modulate and polarize light, play a vital role in the development of optical sensors and optoelectronic devices. Herein, we synthesized a new birefringent crystal [(C10N2H10)(HI2O6)(HIO3)(IO3)] with large birefringence by integrating the large π-conjugated 4,4′-bipyridine group with two types of iodates anions ([IO3]−and [HI2O6]−) characterized by high polarizability anisotropy and strong stereochemically active lone pairs (SCALP). The crystal exhibits a large measured birefringence of 0.171 at 550 nm, surpassing most organic–inorganic hybrid iodate birefringent materials reported in the literature. Theoretical analyses reveal that the optical properties of the crystal arise primarily from the synergistic interactions between the π-conjugated 4,4′-bipyridine group and I–O groups. This research presents an effective method for the strategic integration of large π-conjugated organic cations into iodates, facilitating the design of novel birefringent materials and encouraging further exploration of superior birefringent substances.

ABSTRACTIntroductionStudies have shown the relative cardiovascular safety of hormone replacement therapy (HRT) for women in the general population. Evidence on women with diabetes remains scarce. We aimed to investigate the risk of cardiovascular disease (CVD) in menopausal women with diabetes who use HRT compared to non-users.MethodsSearch across Medline, Embase, Web of Sciences, and Cochrane databases up to November 2023 was conducted. We combined keywords of menopause, diabetes, HRT, and various CVD outcomes. Non-English studies, observational studies other than cohort and case–control, reviews, and conference abstracts were excluded. Bias was checked using validated risk-of-bias tools. Random-effects model was used to calculate pooled relative risks (RR) for similar outcomes.ResultsOut of 7625 identified articles, 19 (6 clinical trials and 13 observational studies) were included, primarily from Europe and the U.S.A. Most studies had moderate risk of bias. Meta-analysis of myocardial infarction (MI) risk from nine observational studies (n =  ~34,626) showed a pooled RR of 0.83 (95% CI 0.62–1.12). Limited data precluded meta-analysis for the clinical trials and other outcomes from observational studies.ConclusionsObservational studies do not suggest an increased risk of MI in menopausal women with diabetes prescribed HRT. Further research with a more robust method is warranted to validate this finding.Prospero registration numberCRD42023479335

The millimeter wave (mmWave) has received considerable interest due to its expansive bandwidth and high frequency. However, a noteworthy challenge arises from its vulnerability to blockages, leading to reduced coverage and achievable rate. To address these limitations, a potential solution is to deploy distributed reconfigurable intelligent surfaces (RISs), which comprise many low-cost and passively reflected elements, and can facilitate the establishment of extra communication links. In this paper, we leverage stochastic geometry to investigate the ergodic coverage probability and the achievable rate in both distributed RISs-assisted single-cell and multi-cell mmWave wireless communication systems. Specifically, we first establish the system model considering the stochastically distributed blockages, RISs and users by the Poisson point process. Then we give the association criterion and derive the association probabilities, the distance distributions, and the conditional coverage probabilities, for two cases of associations between base stations and users without or with RISs. Finally, we use Campbell’s theorem and the total probability theorem to obtain the closed-form expressions of the ergodic coverage probability and the achievable rate. Simulation results verify the effectiveness of our analysis method, and demonstrate that by deploying distributed RISs, the ergodic coverage probability is significantly improved by approximately 50%, and the achievable rate is increased by more than 1.5 times.

This research delves into the innovative application of the optical Stark effect in dynamically guiding polaritons through a Y-shaped potential, forming a polaritonic coupler within a 2D hybrid organic-inorganic perovskite microcavity. The study explores the characteristics of the 2D perovskite, focusing on harnessing the optical Stark-induced energy shift in the polariton branches. The polaritonic coupler, which has a single input and two divergent outputs, is subjected to an external optical Stark pulse, dynamically guiding polaritons between the input and outputs. The research focuses on examining the controllability of the polaritonic coupler through the polariton coupling ratio, highlighting the regulatory role played by the optical Stark effect in this dynamic process. In-depth analyses of the spatial distribution and time evolution of polaritons within the coupler reveal that the optical Stark pulse effectively regulates the polariton coupling ratio, realizing a programmable coupler. This investigation not only advances the fundamental understanding of polariton dynamics within 2D hybrid organic-inorganic perovskite microcavities but also demonstrates the potential for developing optically controlled integrated photonic devices.

ABSTRACTIntroductionAntidepressants and menopause are risk factors which are independently associated with an increased risk of fractures. This review aims to investigate the risk of fragility fractures in women aged 40 and older and prescribed antidepressants.MethodsA literature search was conducted using PubMed, Ovid Embase, Ovid PsychINFO, Web of Science, and Scopus from inception to 1 June 2024. Relevant citations were identified and screened against our inclusion/exclusion criteria. The study population comprised women over 40 years. The risk of fragility fractures was compared between users and non-users of antidepressants. Risk of bias assessment was carried out using the ROBINS-I tool. A meta-analysis of cohort studies was performed to assess fracture risk associated with prescribing of any antidepressant agents, and SSRIs specifically.ResultsOf the 3,676 articles retrieved, five observational studies were found eligible for inclusion (n = 1,240,354). In a meta-analysis of 4 studies, an increased risk of fractures in women was associated with the prescribing of antidepressants (HR = 1.62, 95% CI: 1.15–2.28; I2 = 96.50%) and SSRIs in particular (HR = 1.36, 95% CI: 1.20–1.55; I2 = 40.32%).ConclusionsFindings from this review suggest that prescribing of antidepressants is associated with an increased risk of fractures in women aged 40 and older. Substantial heterogeneity between studies may have affected the results of the meta-analysis.

The properties of the magnetic mold in magnetic mold casting directly determine the quality of the final cast parts. In this study, the magnetic mold properties in magnetic mold casting, were studied utilizing a coupled electromagnetic-structural method through numerical simulation. This study investigated key factors including equivalent stress, the distribution of tensile and compressive stresses, and the area ratio of tensile stress. It compared molds made entirely of magnetic materials with those made partially of magnetic materials. Simulation results indicate that as current increases from 4 A to 8 A, both the initial magnetic mold and the material-replaced magnetic mold initially show an increasing trend in equivalent stress, tensile-compressive stress, and the area ratio of tensile stress, peaking at 6 A before declining. After material replacement, the area ratio of tensile stress at 6 A decreases to 19.84%, representing a reduction of 29.72%. Magnetic molds comprising a combination of magnetic and non-magnetic materials exhibit sufficient strength and a reduced area ratio of tensile stress compared to those made entirely from magnetic materials. This study provides valuable insights for optimizing magnetic mold casting processes and offers practical guidance for advancing the application of magnetic molds.

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n= 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n= 130); and paclitaxel with cisplatin (TP group; n= 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1–32.0, P< 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7–18.1, P= 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034.

Objective This study aimed to analyze the malignant probability of thyroid nodules diagnosed as indeterminate cytology, including atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), and investigate the diagnostic value of combining BRAF V600E gene testing within this classification.Methods We conducted a retrospective analysis of 126 patients who underwent fine-needle aspiration (FNA) examination of thyroid nodules and subsequent surgical treatment at Beijing Haidian Hospital between October 2021 and November 2022. Among them, there were 22 male and 104 female patients, aged between 18 and 75 years old. Surgical pathology results were considered the gold standard for diagnosing the nature of thyroid nodules, evaluating the malignant incidence of cytological results categorized as AUS/FLUS. Fisher’s exact test and diagnostic test evaluation methods were used to analyze the discriminatory diagnostic efficacy of preoperative FNA combined with BRAF V600E gene testing for papillary thyroid carcinoma (PTC). Statistical analysis was performed using SPSS 22.0 software.Results In PTC patients, the BRAF V600E gene mutation rate was 87.93% (102/116). Within the category of FNA results as AUS/FLUS, the proportion of PTC was 60.00% (15/25). The specificity, sensitivity, positive predictive value, and negative predictive value of the BRAF V600E gene mutation in diagnosing PTC within the AUS/FLUS category were 10/10, 6/15, 6/6, and 10/19, respectively. The BRAF V600E gene mutation significantly increased the detection rate of PTC in patients classified under this cytology (P= 0.028, <0.05).Conclusion Preoperative FNA combined with BRAF V600E gene mutation testing significantly enhances the malignant detection rate of thyroid nodules diagnosed cytologically as AUS/FLUS. This combined approach provides a potent tool to improve diagnostic accuracy in this indeterminate classification.

Herein, we report a transition-metal-free C–H bond sulfoximidation protocol of sulfonyl hydrazones with hypervalent iodine(III) reagents. A library of novel N-sulfaneylidenehydrazonamides was constructed via chemoselective C–N bond formation reactions at aldehyde C–H bonds of sulfonyl hydrazones in the presence of a base. The reaction demonstrated broad substrate group diversity under exceedingly mild reaction conditions, and excellent yields were achieved at room temperature.

This study introduces MOVTDMA, a novel directional reception time-division multiple access (TDMA) protocol optimized for underwater acoustic sensor network (UASN) using a multiobjective optimization algorithm. To address the high-data-rate communication requirements of underwater acoustic networks, MOVTDMA utilizes the directional reception capabilities of vector hydrophones (VHPs) to enhance network throughput and robustness through spatial reuse technology. By scheduling transmission slots and VHPs’ steering angles, the protocol enables parallel data transmission across multiple links, effectively maximizing network performance. The proposed protocol models the scheduling problem as a multiobjective optimization problem and efficiently solves it using the nondominated sorting genetic algorithm II (NSGA-II) algorithm. Utilizing a novel labeled tree-based starting slot encoding scheme, steering angle prior information, and a hash-based memory search mechanism, MOVTDMA optimizes convergence speed and prevents redundant calculations. Simulation results demonstrate significant improvements in network throughput and robustness compared to existing TDMA-based media access control (MAC) protocols in UASNs, highlighting MOVTDMA’s potential in high-data-rate underwater applications. This approach offers a promising solution to the challenges of underwater acoustic communications, balancing network throughput with robustness and effectively managing spatial reuse in dense acoustic environments.

In this letter, we investigate the beam training problem in the multi-user millimeter wave (mmWave) communication system, where multiple reconfigurable intelligent surfaces (RISs) are deployed to improve the coverage and the achievable rate. However, existing beam training techniques in mmWave systems suffer from high complexity (i.e., exponential order) and low identification accuracy. To address these problems, we propose a novel hashing multi-arm beam (HMB) training scheme that reduces the training complexity to the logarithmic order with the high accuracy. Specifically, we first design a generation mechanism for HMB codebooks. Then, we propose a demultiplexing algorithm based on the soft decision to distinguish signals from different RIS reflective links. Finally, we utilize a multi-round voting mechanism to align the beams. Simulation results show that the proposed HMB training scheme enables simultaneous training for multiple RISs and multiple users, and reduces the beam training overhead to the logarithmic level. Moreover, it also shows that our proposed scheme can significantly improve the identification accuracy by at least 20% compared to the existing beam training techniques.

This article presents a novel aperture-shared architecture applied in integration of millimeter-wave (mmW) phased array and sub-6 GHz antenna using diversified metasurface structures. First, a miniaturized mmW antenna element based on overlapped metasurface is designed, and then a wide-angle scanning phased array using the above elements is constructed with some U-shaped decoupling paths. In addition, a novel electromagnetic-transparent (EM-transparent) sub-6 GHz antenna formed by four square ring metasurface (SRMS) cells is proposed and located above the mmW array in the same aperture. To further reduce the shielding effects, a serial of frequency-selective surface (FSS) structures with high-impedance property are loaded around the SRMS for enhancing the transparent property at mmW band. Finally, the aperture-shared antenna array is implemented using the low-temperature-cofired ceramic (LTCC) technology; moreover, their feeding networks are highly integrated together. As a result, the mmW array can achieve a wide beam scanning in the E-plane from −55° to 55° at 24.25–29.5 GHz and high isolation over 20 dB; meanwhile, the sub-6 GHz antenna exhibits good radiation at 3.3–3.6 GHz. Compared with other works, it not only realizes aperture-shared integration of mmW phased array and sub-6 GHz antenna with largest frequency ratio but also ensures wide-angle scanning performance, which can be potentially applied in future multiband base-station antennas.

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure–activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14dshares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14dsignificantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14das a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.

This study aims to investigate the phase composition, microstructure, and mechanical properties of three refractory high-entropy alloys (RHEAs): Al7(NbTiZr)93, Al7(NbTiZrMo)93, and Al7(NbTiZrTa)93. The as-cast Al7(NbTiZr)93alloy exhibits a single-phase BCC structure, with a yield strength (YS) of 1050 MPa at room temperature. The addition of Mo and Ta leads to the formation of Al7(NbTiZrMo)93and Al7(NbTiZrTa)93alloys with BCC-B2and B2-FCC dual-phase structures, whose YS values reach 1741 MPa and 2350 MPa, respectively. At 800 °C, trace amounts of ordered B2phase are generated in the Al7(NbTiZr)93matrix, and the YS decreases from 1050 MPa at room temperature to 219 MPa at 800 °C. In the Al7(NbTiZrMo)93alloy, the 10 nm B2precipitates grow to several hundred nanometers, and the YS decreases to 431 MPa after compression at 800 °C. In the Al7(NbTiZrTa)93alloy, the grid B2-FCC structure at room temperature transforms into a disordered BCC structure at 800 °C, yet possessing the YS of 908 MPa and demonstrating acceptable ductility. Moreover, Ta exhibits the better structural and performance matching than Mo in AlNbTiZr-based RHEAs. Therefore, it opens up new prospects for regulating the structure and high-temperature performance of AlNbTiZr-based RHEAs.

Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population.