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Abstract Wearable ultrasound imaging technology has become an emerging modality for the continuous monitoring of deep-tissue physiology, providing crucial health and disease information. Fast volumetric imaging that can provide a full spatiotemporal view of intrinsic 3D targets is desirable for interpreting internal organ dynamics. However, existing 1D ultrasound transducer arrays provide 2D images, making it challenging to overcome the trade-off between the temporal resolution and volumetric coverage. In addition, the high driving voltage limits their implementation in wearable settings. With the use of microelectromechanical system (MEMS) technology, we report an ultrasonic phased-array transducer, i.e., a 2D piezoelectric micromachined ultrasound transducer (pMUT) array, which is driven by a low voltage and is chip-compatible for fast 3D volumetric imaging. By grouping multiple pMUT cells into one single drive channel/element, we propose an innovative cell–element–array design and operation of a pMUT array that can be used to quantitatively characterize the key coupling effects between each pMUT cell, allowing 3D imaging with 5-V actuation. The pMUT array demonstrates fast volumetric imaging covering a range of 40 mm × 40 mm × 70 mm in wire phantom and vascular phantom experiments, achieving a high temporal frame rate of 11 kHz. The proposed solution offers a full volumetric view of deep-tissue disorders in a fast manner, paving the way for long-term wearable imaging technology for various organs in deep tissues.

Wide-angle imaging and spectral detection play vital roles in tasks such as target tracking, object classification, and anti-camouflage. However, limited by their intrinsically different architectures, as determined by frequency dispersion requirements, their simultaneous implementation in a shared-aperture system is difficult. Here, we propose a novel concept to realize reconfigurable dual-mode detection based on electrical-control tunable metasurfaces. As a proof-of-concept demonstration, the simultaneous implementation of wide-angle imaging and polarization-spectral detection in a miniature shared-aperture meta-optical system is realized for the first time via the electrical control of cascaded catenary-like metasurfaces. The proposed system supports the imaging (spectral) resolution of approximately 27.8 line-pairs per millimeter (lp·mm−1; ∼80 nm) for an imaging (spectral) mode from 8 to 14 μm. This system also bears a large field of view of about 70°, enabling multi-target recognition in both modes. This work may promote the miniaturization of multifunctional optical systems, including spectrometers and polarization imagers, and illustrates the potential industrial applications of meta-optics in biomedicine, security, space exploration, and more.

Diabetes, a prevalent chronic condition, significantly increases the risk of mortality from COVID-19, yet the underlying mechanisms remain elusive. Emerging evidence implicates Cathepsin L (CTSL) in diabetic complications, including nephropathy and retinopathy. Our previous research identified CTSL as a pivotal protease promoting SARS-CoV-2 infection. Here, we demonstrate elevated blood CTSL levels in individuals with diabetes, facilitating SARS-CoV-2 infection. Chronic hyperglycemia correlates positively with CTSL concentration and activity in diabetic patients, while acute hyperglycemia augments CTSL activity in healthy individuals. In vitro studies reveal high glucose, but not insulin, promotes SARS-CoV-2 infection in wild-type cells, with CTSL knockout cells displaying reduced susceptibility. Utilizing lung tissue samples from diabetic and non-diabetic patients, alongside Leprdb/dbmice and Leprdb/+mice, we illustrate increased CTSL activity in both humans and mice under diabetic conditions. Mechanistically, high glucose levels promote CTSL maturation and translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. Our findings underscore the pivotal role of hyperglycemia-induced CTSL maturation in diabetic comorbidities and complications.

Anaplastic lymphoma kinase (ALK) inhibitors are the recommended treatment of ALK-rearranged non-small cell lung cancer but are prone to eventual drug resistance.Herein we report a 45-year-old Asian woman diagnosed with EML4-ALK rearranged lung adenocarcinoma. Small cell lung cancer-like phenotypic transformation occurred when resistance to crizotinib treatment. Next-generation sequencing was performed and detected an ALK rearrangement co-existent with a TP53 gene mutation in the small cell specimens. The patient had a good response to alectinib with a progression-free survival >7 months. After disease progression, newly emerged ALK p.G1269A and p.L1196 M gene mutations co-existent with ALK rearrangement were detected. The patient had a good initial response to ceritinib treatment, which last for >12 months. After ceritinib failure, however, more complicated mutations within the ALK kinase domain (p.G1269A, p.L1196 M, newly emerged p.D1203 N, and p.L1122V) were detected. Ultimately, due to terminal rapid progression and resistance to lorlatinib, the overall survival was nearly 3 years.Our case showed that next-generation ALK-tyrosine kinase inhibitors (TKIs) may be an appropriate choice after transformation to small cell lung cancer and failure to one ALK-TKI. Sequential biopsies and gene mutation monitoring are important to arrange the sequence of different generation ALK-TKIs. Appropriate sequential therapies may yield a prolonged response with a satisfactory quality of life in patients with advanced ALK-rearranged non-small cell lung cancer.

Abstract As a modernist writer writing through the two World Wars and witnessing the decline of British imperial power through the decay of her own class, the Anglo-Irish Ascendancy, most of Elizabeth Bowen’s (1899–1973) writing is that of trauma. Many critics have suggested that modernist writing provides a response to the traumas of the era and resonates with the Freudian model of trauma, which regards the syndrome of traumatic events as post-traumatic. This essay challenges the previous studies regarding modernist writing of trauma as post-traumatic, by introducing Saint-Amour’s concept of a “pre-traumatic stress syndrome” to study Bowen’s two novels about wars, The Last September and The Heat of the Day. The essay holds that in Bowen’s writing, anticipation and anxiety arising before the war can also inflict psychic damage, just like the actual war. The essay demonstrates how Bowen’s writing about wars adds a new approach to literary trauma studies, which have concentrated almost solely on the aftermath of catastrophes or violence. Interpreting Bowen’s writing as pre-trauma not only provides a better understanding of the psychological condition of people during the wars but brings a new perspective to trauma studies as well.

Delaying an electromagnetic (EM) wave pulse on a thin screen for a significant time before releasing it is highly desired in many applications, such as optical camouflage, information storage, and wave–matter interaction boosting. However, available approaches to achieve this goal either require thick and complex systems or suffer from low efficiencies and a short delay time. This paper proposes an ultra-thin meta-platform that can significantly delay an EM-wave pulse after reflection. Specifically, our meta-platform consists of three meta-surfaces integrated together, of which two are responsible for efficiently coupling incident EM-wave pulse into surface waves (SWs) and vice versa, and the third one supports SWs exhibiting significantly reduced group velocity. We employ theoretical model analyses, full-wave simulations, and microwave experiments to validate the proposed concept. Our experiments demonstrate a 13 ns delay of an EM pulse centered at 12.975 GHz, enabled by a λ/8-thick and 38-λ-long meta-device with an efficiency of 32% (or 70%) with (or without) material loss taken into account. A larger delay time can be enabled by devices with larger sizes considering that the SWs group velocity of our device can be further reduced via dispersion engineering. These findings establish a new road for delaying an EM-wave pulse with ultra-thin screens, which may lead to many promising applications in integration optics.

Formulating warning signals for canopy growth status at different stages are an effective way to dynamically regulate the water and fertilizer management based on the relationship between growth information and orchard productivity. In the study, the response of leaf nitrogen content (LNC), leaf area index (LAI), fruit yield, quality and water and nitrogen use efficiency to irrigation levels and nitrogen rates was investigated in a field experiment from 2017 to 2022. Principal component analysis was used to construct an orchard production comprehensive evaluation index (OPCEI) to assess orchard productivity, and the relationship between LAI, LNC and OPCEI was analyzed by the structural equation modeling. The results showed that nitrogen rates had significant effect on OPCEI in the different years, but irrigation levels had significant effect in 2019 and 2021. Compared to no fertilization, the OPCEI of 120, 240, and 360 kg ha−1 under low irrigation amount showed average increased 28.90%, 48.54%, and 25.85%, while it increased by an average of 33.51%, 55.65%, and 32.44% for 120, 240, and 360 kg ha−1 under high irrigation amount. Also, low irrigation amount did not significantly reduce OPCEI at 240 kg ha−1 compared to high irrigation amount. Structural equation modeling revealed that LNC had significant positive effect on fruit yield, while had significant negative effect on total soluble solids. Furthermore, LAI had a significant positive effect on fruit yield and sugar-acid ratio. On the basis of the relationship of LAI, LNC and OPCEI, the reference value of LNC was proposed. The suitable range of LNC in the shoot growth and young fruit stage is 2.96%-3.79% and 2.62%-3.30%, and that is 2.43%-3.17%, 2.21%-2.97%, and 2.13%-2.63% in the early, middle and late fruit expansion stage, respectively. The study results provide a basis for canopy nitrogen diagnosis, which is guide for achieving precise nitrogen application in apple orchards.

Metalenses have gained significant attention and have been widely utilized in optical systems for focusing and imaging, owing to their lightweight, high-integration, and exceptional-flexibility capabilities. Traditional design methods neglect the coupling effect between adjacent meta-atoms, thus harming the practical performance of meta-devices. The existing physical/data-driven optimization algorithms can solve the above problems, but bring significant time costs or require a large number of data-sets. Here, we propose a physics-data-driven method employing an “intelligent optimizer” that enables us to adaptively modify the sizes of the meta-atom according to the sizes of its surrounding ones. The implementation of such a scheme effectively mitigates the undesired impact of local lattice coupling, and the proposed network model works well on thousands of data-sets with a validation loss of 3×10−3. Based on the “intelligent optimizer”, a 1-cm-diameter metalens is designed within 3 hours, and the experimental results show that the 1-mm-diameter metalens has a relative focusing efficiency of 93.4% (compared to the ideal focusing efficiency) and a Strehl ratio of 0.94. Compared to previous inverse design method, our method significantly boosts designing efficiency with five orders of magnitude reduction in time. More generally, it may set a new paradigm for devising large-aperture meta-devices.

A novel type of austenite–martensite dual-phase laminate steel with a yield strength of 2.2 GPa, ultimate tensile strength of 2.5 GPa, uniform elongation of 9.4% and total elongation of 12% was produced. Such unexpectable mechanical properties were mainly due to the synergistic strengthening of nanolaminate microstructure, high densities of dislocations and nanoprecipitates. The high uniform elongation at very high stress could be attributed to the strongly enhanced work hardening rate, mainly enabled by transformation-induced plasticity (TRIP) of the austenite reverted by annealing, as well as the cooperative deformation and stress/strain partitioning between the austenite–martensite stacked nanolaminate.

Abstract Aim Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions. Subjects and method In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C > A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data. Results The most frequent base substitutions were G:C > A:T transition in all the areas investigated. The G:C > A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C > A:T transition in CpG sites and A:T > G:C mutation was more prevalent in Asian countries. Conclusion The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.

Abstract Freely switching light transmission and absorption via an achromatic reflectionless screen is highly desired for many photonic applications (e.g., energy-harvesting, cloaking, etc.), but available meta-devices often exhibit reflections out of their narrow working bands. Here, we rigorously demonstrate that an optical metasurface formed by two resonator arrays coupled vertically can be perfectly reflectionless at all frequencies below the first diffraction mode, when the near-field (NF) and far-field (FF) couplings between two constitutional resonators satisfy certain conditions. Tuning intrinsic loss of the system can further modulate the ratio between light transmission and absorption, yet keeping reflection diminished strictly. Designing/fabricating a series of metasurfaces with different inter-resonator configurations, we experimentally illustrate how varying inter-resonator NF and FF couplings can drive the system to transit between different phase regions in a generic phase diagram. In particular, we experimentally demonstrate that a realistic metasurface satisfying the discovered criteria exhibits the desired achromatic reflectionless property within 160–220 THz (0–225 THz in simulation), yet behaving as a perfect absorber at ~ 203 THz. Our findings pave the road to realize meta-devices exhibiting designable transmission/absorption spectra immune from reflections, which may find many applications in practice.

Imaging polarimetry is one of the most widely used analytical technologies for object detection and analysis. To date, most metasurface-based polarimetry techniques are severely limited by narrow operating bandwidths and inevitable crosstalk, leading to detrimental effects on imaging quality and measurement accuracy. Here, we propose a crosstalk-free broadband achromatic full Stokes imaging polarimeter consisting of polarization-sensitive dielectric metalenses, implemented by the principle of polarization-dependent phase optimization. Compared with the single-polarization optimization method, the average crosstalk has been reduced over three times under incident light with arbitrary polarization ranging from 9 μm to 12 μm, which guarantees the measurement of the polarization state more precisely. The experimental results indicate that the designed polarization-sensitive metalenses can effectively eliminate the chromatic aberration with polarization selectivity and negligible crosstalk. The measured average relative errors are 7.08%, 8.62%, 7.15%, and 7.59% at 9.3, 9.6, 10.3, and 10.6 μm, respectively. Simultaneously, the broadband full polarization imaging capability of the device is also verified. This work is expected to have potential applications in wavefront detection, remote sensing, light-field imaging, and so forth.

The development of low-cost and eco-friendly gel polymer electrolytes (GPEs) with a wide window, ideal compatibility, and structural stability is an effective measure to achieve safe high-energy-density lithium-metal batteries. Herein, a biodegradable composite polyacrylonitrile/poly-L-lactic acid nanofiber membrane (PAL) is synthesized and used as a robust skeleton for GPEs. The 3D nanofiber membrane (PAL-3-C12) prepared with an adjusted weight ratio of polyacrylonitrile (PAN)/poly-L-lactic acid (PLLA) and spinning solution concentration delivers decent thermal stability, biodegradability, and liquid electrolyte absorbability. The “passivation effect” of PAN upon lithium metal is effectively alleviated by hydrogen bonds formed in the PAL chains. These advantages enable PAL GPEs to work stably to 5.17 ​V while maintaining high ionic conductivity as well as excellent corrosion resistance and dielectric properties. The interfacial compatibility of optimized GPEs promotes the stable operation of a Li||PAL-3-C12 GPEs||Li symmetric battery for 1000 ​h at 0.15 ​mA ​cm−2/0.15 ​mA ​h cm−2, and the LiFePO4 full cell retains capacity retention of 97.63% after 140 cycles at 1C.

BackgroundUntreated maternal postpartum depression (PPD) has consequences for children's physical growth, but no published study has evaluated changes in this effect over time. Here we therefore aimed to evaluate the dynamic effects of PPD on the physical growth of children in a prospective birth cohort.MethodsBetween 2015 and 2019, 960 mother-child pairs in Changsha, China were followed up when the child was aged 1–48 months. Data were obtained through household surveys. The mothers' depressive symptoms were measured using the Edinburgh Postpartum Depression Scale (EPDS) at 1 month postpartum. Linear mixed models were used to examine the changes in the association of PPD and EPDS scores with physical growth in six different age groups of children between 1 and 48 months.ResultsA total of 604 mother-child pairs completed the follow-up, and 3.3% of mothers reported PPD. No associations were found between PPD and weight or height growth at any age. While EPDS scores were associated with weight gain (β = −0.014, 95% CI (−0.025, −0.002), P = 0.024) and height growth (β = −0.044, 95% CI (−0.084, −0.004), P = 0.030) rates at 1–3 months, no associations were found in older children.LimitationsThe number of mothers who reported PPD was relatively small, and the measurement of PPD was not continuously taken.ConclusionsAfter adjustments for confounders, no dynamic association was found between PPD and children's weight and height growth. EPDS scores, in contrast, did negatively affect children's weight and height growth at age 1–3 months, but this effect was not long-lasting.

Abstract. Background:. To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19. Methods:. This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable. Results:. A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%–48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151–3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350–67.410, P 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions:. SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events. Trial registration:. Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1

Abstract The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important target for vaccine and drug development. However, the rapid emergence of variant strains with mutated S proteins has rendered many treatments ineffective. Cleavage of the S protein by host proteases is essential for viral infection. Here, we discovered that the S protein contains two previously unidentified Cathepsin L (CTSL) cleavage sites (CS-1 and CS-2). Both sites are highly conserved among all known SARS-CoV-2 variants. Our structural studies revealed that CTSL cleavage promoted S to adopt receptor-binding domain (RBD) “up” activated conformations, facilitating receptor-binding and membrane fusion. We confirmed that CTSL cleavage is essential during infection of all emerged SARS-CoV-2 variants (including the recently emerged Omicron variant) by pseudovirus (PsV) infection experiment. Furthermore, we found CTSL-specific inhibitors not only blocked infection of PsV/live virus in cells but also reduced live virus infection of ex vivo lung tissues of both human donors and human ACE2-transgenic mice. Finally, we showed that two CTSL-specific inhibitors exhibited excellent In vivo effects to prevent live virus infection in human ACE2-transgenic mice. Our work demonstrated that inhibition of CTSL cleavage of SARS-CoV-2 S protein is a promising approach for the development of future mutation-resistant therapy.

Aqueous Zn metal batteries have become competitive electrochemical energy storage systems owing to their material abundance, low cost, high capacity, and nontoxicity. Nevertheless, the notorious Zn dendrites and poor anode reversibility caused by the insulating by-products and “dead Zn” are still formidable challenges for their practical application. Herein, an SnS-based layer coated on the Zn anode is reported to tackle these problems. The semiconducting SnS with a higher work function can drive the electrons from the Zn anode, which constructs a polarized interface between the SnS layer and Zn. The semiconducting importance of the coating layer is verified through theoretical simulations, which can migrate the polarization layer from the electrode surface to a well-protected spot beneath the coating layer. This polarization interface is effective in homogenizing the Zn2+ flux and repelling the anions from electrochemical corrosion. Compared with the bare Zn, the SnS-coated Zn anode exhibits a notable 14.7-fold enhancement in plating/stripping lifetime (over 3000 ​h), high reversibility (with CE of 99.74%), and superior stability in full cells when paired with vanadium- and manganese-based cathodes.

Abstract Background Although with the impressive efficacy, several patients showed intrinsic resistance or an unsatisfactory response to Osimertinib. We aim to explore the impact of clinical and molecular features on efficacy and outcome of patients with EGFR T790M-mutation non-small cell lung cancer (NSCLC) receiving second-line Osimertinib. Methods Patients with EGFR T790M-mutant NSCLC who had acquired resistance to the first-generation EGFR TKI and then received Osimertinib as second-line treatment were included. Patients’ demographic and clinical information, as well as molecular data were extracted from electronic medical records. The impact of clinical and molecular features on treatment response and patients’ outcome were assessed. Results Among the 99 patients, 60 patients were tissue/pleural effusion T790M positive and 69 patients were plasma positive with a median PFS of 12.1 m and 9.9 m (P = 0.25), respectively. In addition, median PFS were similar between patients of plasma T790M + and patients of plasma T790M- (P = 0.94). The Pearson correlation test showed no significant relationship between plasma T790M abundance and PFS (r = 0.074, P = 0.546). In subgroup analyses, PFS was significantly improved in elder patients (P = 0.009) and patients with longer PFS to the first-generation EGFR TKI (P = 0.0008), while smokers tended to have worse PFS compared with non-smokers (P = 0.064). PARP1 mutant-type patients had a worse PFS compared with wild-type group (P = 0.0003). Patients with MYC amplification also had a worse PFS than MYC wild-type patients (P = 0.016). A significant PFS shrinkage was observed in TMB-High group as 6.77 m, compared with 19.10 m in TMB-Low group. The multivariate Cox analysis revealed that years ≥ 65 was an independent positive feature for PFS, while PARP1 mutation and TMB-H were negative features for PFS. Conclusion In conclusion, our findings in this study demonstrated that clinical and molecular features can be served as predictive biomarkers to stratify patients with EGFR T790M-mutant NSCLC receiving second-line Osimertinib.

Abstract Aqueous zinc metal batteries are noted for their cost-effectiveness, safety and environmental friendliness. However, the water-induced notorious issues such as continuous electrolyte decomposition and uneven Zn electrochemical deposition remarkably restrict the development of the long-life zinc metal batteries. In this study, zwitterionic sulfobetaine is introduced to copolymerize with acrylamide in zinc perchlorate (Zn(ClO4)2) solution. The designed gel framework with hydrophilic and charged groups can firmly anchor water molecules and construct ion migration channels to accelerate ion transport. The in situ generated hybrid interface, which is composed of the organic functionalized outer layer and inorganic Cl− containing inner layer, can synergically lower the mass transfer overpotential, reduce water-related side reactions and lead to uniform Zn deposition. Such a novel electrolyte configuration enables Zn//Zn cells with an ultra-long cycling life of over 3000 h and a low polarization potential (~ 0.03 V) and Zn//Cu cells with high Coulombic efficiency of 99.18% for 1000 cycles. Full cells matched with MnO2 cathodes delivered laudable cycling stability and impressive shelving ability. Besides, the flexible quasi-solid-state batteries which are equipped with the anti-vandalism ability (such as cutting, hammering and soaking) can successfully power the LED simultaneously. Such a safe, processable and durable hydrogel promises significant application potential for long-life flexible electronic devices.

Abstract Multifunctional terahertz (THz) devices in transmission mode are highly desired in integration‐optics applications, but conventional devices are bulky in size and inefficient. While ultra‐thin multifunctional THz devices are recently demonstrated based on reflective metasurfaces, their transmissive counterparts suffer from severe limitations in efficiency and functionality. Here, based on high aspect‐ratio silicon micropillars exhibiting wide transmission‐phase tuning ranges with high transmission‐amplitudes, a set of dielectric metasurfaces is designed and fabricated to achieve efficient spin‐multiplexed wavefront controls on THz waves. As a benchmark test, the photonic‐spin‐Hall‐effect is experimentally demonstrated with a record high absolute efficiency of 92% using a dielectric metasurface encoded with geometric phases only. Next, spin‐multiplexed controls on circularly polarized THz beams (e.g., anomalous refraction and focusing) are experimentally demonstrated with experimental efficiency reaching 88%, based on a dielectric meta‐device encoded with both spin‐independent resonant phases and spin‐dependent geometric phases. Finally, high‐efficiency spin‐multiplexed dual holographic images are experimentally realized with the third meta‐device encoded with both resonant and geometric phases. Both near‐field and far‐field measurements are performed to characterize these devices, yielding results in agreement with full‐wave simulations. The study paves the way to realize multifunctional, high‐performance, and ultra‐compact THz devices for applications in biology sensing, communications, and so on.

Aim: The purpose of this study was to investigate the mechanical and electrophysiological effects of emodin on BK channels in the IRASMCs, of the rat. Methods: Isolated interlobar renal artery was used for vascular reactivity measurements using a pressure myograph system. Electrophysiological measurements of single vascular smooth muscle cells were conducted using whole-cell and cell-attached patch-clamp recording. Laser scanning confocal microscope technology was used to measure cytosolic calcium ion signals. Key results: Emodin relaxed the interlobar renal artery and enhanced the outward currents amplitude of IRASMCs in a concentration-dependent manner, and IbTX inhibited these emodin-induced outward currents. Incubation of IRASMCs in a calcium ion free medium for 30 min decreased the observed effects of emodin on IRASMCs membrane currents. Furthermore, the application of nimodipine, an L-Type calcium ion channel blocker, ryanodine, a ryanodine receptor modifier, and heparin, an IP3 receptor blocker, decreased the emodin-induced BK channel currents, respectively. BAPTA-AM, a selective calcium ion chelator, abolished the emodin-induced BK channel currents. Emodin repolarized cytomembrane and enhanced BK channel open probabilities and elevated cytosolic calcium ion concentration. Conclusion: The vasorelaxant effect of emodin on vessels is mediated through the activation of BK channels.

Unrestricted manipulations on terahertz (THz) waves are highly desired in integration-optics, but THz devices based on conventional materials are usually bulky in size. Although all-silicon metasurfaces have exhibited great capabilities in manipulating THz waves, most of them are less efficient and have limited functionalities. In this work, we first design a silicon meta-atom structure consisting of a high-aspect-ratio (AR) micro-pillar that exhibits nearly perfect transmission and large transmission phase of THz wave, and systemically study how the fabrication quality (e.g., steepness of the sidewall and the vertical thickness distribution) may influence the final performance of a functional metasurface constructed with such meta-atoms. After experimentally examining how two working phases in the deep-reactive-ion-etch technology (i.e., the etch and passivation phases) influence the quality of the fabricated meta-devices, we develop an optimized Bosch process to realize high-AR (~20:1) all-silicon metasurfaces by balancing two working phases. We finally design/fabricate a high-AR silicon metasurface and experimentally demonstrate that it behaves as a high-efficiency half-wave-plate for THz waves in transmission geometry. Our results pave the avenue to realize ultra-compact THz meta-devices with high performance in transmission geometry, which is highly desirable for THz applications.

Brain structural and functional abnormalities have been shown to be involved in the neurobiological underpinnings of bulimia nervosa (BN), while the mechanisms underlying this dysregulation are unclear. The main goal of this investigation was to explore the presence of brain structural alterations and relevant functional changes in BN. We hypothesized that BN patients had regional gray matter volume abnormalities and corresponding resting-state functional connectivity (rsFC) changes compared with healthy controls. Thirty-one BN patients and twenty-eight matched healthy controls underwent both high-resolution T1-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Structural analysis was performed by voxel-based morphometry (VBM), with subsequent rsFC analysis applied by a seed-based, whole-brain voxelwise approach using the abnormal gray matter volume (GMV) region of interest as the seed. Compared with the controls, the BN patients showed increased GMV in the left medial orbitofrontal cortex (mOFC). The BN patients also exhibited significantly increased rsFC between the left mOFC and the right superior occipital gyrus (SOG) and decreased rsFC between the left mOFC and the left precentral gyrus, postcentral gyrus, and supplementary motor area (SMA). Furthermore, the z values of rsFC between the left mOFC and right SOG was positively correlated with the Dutch Eating Behavior Questionnaire-external eating scores. Findings from this investigation further suggest that the mOFC plays a crucial role in the neural pathophysiological underpinnings of BN, which may lead to sensorimotor and visual regions reorganization and be related to representations of body image and the drive behind eating behavior. These findings have important implications for understanding neural mechanisms in BN and developing strategies for prevention.

This work achieves drastic fluorescence enhancement of NIR single-molecule based on asymmetric plasmonic nano-antenna, by fine-tuning the near- and far- field properties of plasmonic mode.

ABSTRACT: Background: It is necessary to determine the optimal treatment for melanoma as the incidence of melanoma is increasing every year. In this study, we conducted a meta-analysis to compare the effectiveness of available treatments for melanoma. Methods: The index keywords “melanoma” and “treatment” were used to search the PubMed, Cochrane Library, Web of Science, and Embase databases, and the articles were limited to randomized controlled trials. The search was filtered for articles published until February 2020, and articles were independently extracted by two reviewers. Network meta-analysis (Stata® 14.0 software network package, Stata Corp LLC TX, USA) was used to compare the effectiveness of the mentioned treatments of melanoma. Results: A total of 616 articles were screened of which 6 were selected for meta-analysis, involving 5 treatment measures and 2 047 patients (those who were not followed up on were excluded). The treatment strategies reported for melanoma included tumor necrosis factor (L19-TNFα) and interleukin-2 (L19IL2) in combination with dacarbazine (L19IL2 + DTIC), DTIC, programmed cell death-1 plus cytotoxic T cell antigen-4 (PD-1 + CTLA-4), PD-1, and CTLA-4. Conclusion: Among L19IL2 + DTIC, DTIC, PD-1 + CTLA-4, PD-1, and CTLA-4, CTLA-4 is found to be the best treatment method for melanoma. Our study findings provide a reference for the clinical treatment of melanoma and can clarify the direction for setting up controlled clinical trials.

Abstract With inherent orthogonality, both the spin angular momentum (SAM) and orbital angular momentum (OAM) of photons have been utilized to expand the dimensions of quantum information, optical communications, and information processing, wherein simultaneous detection of SAMs and OAMs with a single element and a single-shot measurement is highly anticipated. Here, a single azimuthal-quadratic phase metasurface-based photonic momentum transformation (PMT) is illustrated and utilized for vortex recognition. Since different vortices are converted into focusing patterns with distinct azimuthal coordinates on a transverse plane through PMT, OAMs within a large mode space can be determined through a single-shot measurement. Moreover, spin-controlled dual-functional PMTs are proposed for simultaneous SAM and OAM sorting, which is implemented by a single spin-decoupled metasurface that merges both the geometric phase and dynamic phase. Interestingly, our proposed method can detect vectorial vortices with both phase and polarization singularities, as well as superimposed vortices with a certain interval step. Experimental results obtained at several wavelengths in the visible band exhibit good agreement with the numerical modeling. With the merits of ultracompact device size, simple optical configuration, and prominent vortex recognition ability, our approach may underpin the development of integrated and high-dimensional optical and quantum systems.

Abstract Vectorial optical fields (VOFs) exhibiting arbitrarily designed wavefronts and polarization distributions are highly desired in photonics. However, current methods to generate them either require complicated setups or exhibit limited functionalities, which is unfavorable for integration-optics applications. Here, we propose a generic approach to efficiently generate arbitrary VOFs based on metasurfaces exhibiting full-matrix yet inhomogeneous Jones-matrix distributions. We illustrate our strategy with analytical calculations on a model system and an experimental demonstration of a meta-device that can simultaneously deflect light and manipulate its polarization. Based on these benchmark results, we next experimentally demonstrate the generation of a far-field VOF exhibiting both a vortex wavefront and an inhomogeneous polarization distribution. Finally, we design/fabricate a meta-device and experimentally demonstrate that it can generate a complex near-field VOF—a cylindrically polarized surface plasmon wave possessing orbital angular momentum—with an efficiency of ~34%. Our results establish an efficient and ultracompact platform for generating arbitrary predesigned VOFs in both the near- and far-fields, which may find many applications in optical manipulation and communications.

The aim of this study is to fabricate high-strength steel with exceptional yield strength and superior ductility by employing a novel design approach of nanolamellar/equiaxial crystal “sandwich” heterostructures, utilizing rolling and electron-beam-welding techniques. The microstructural heterogeneity of the steel is manifested in the phase content and grain size, ranging from nanolamellae comprising a small quantity of martensite on both sides to the completely coarse austenite in the center, which are interconnected via gradient interfaces. The structural heterogeneity and phase-transformation-induced plasticity (TIRP) offer remarkable strength and ductility for the samples. Furthermore, the synergistic confinement of the heterogeneous structures leads to the formation of Lüders bands, which exhibit stable propagation under the TIRP effect and impede the onset of plastic instability, ultimately resulting in a significant improvement in the ductility of the high-strength steel.

Theoretically, the topological charge l in the vortex can be any integer or fraction, thus the vortex carrying different topological charges can form an infinitely orthogonal orbital angular momentum state space, which can provide new dimensional resources for optical communication. However, high-capacity optical communication requires low delay, thus real-time detection of the OAM is significant for communication. Metasurfaces have the characteristics of low loss, ultra-thin, easy integration, and flexible phase controls, which provide a meaningful way to realize integrated OAM generation and detection. Here, an optimized streamlined metasurface (OSM) is presented, which can detect high-order vortex beams in a single, simple, and rapid manner by photon momentum transformation (PMT). Since different vortices are converted into focusing modes with distinct azimuthal coordinates on a transverse plane through PMT, a single measurement can determine OAMs in an ample mode space. In addition, the OSM can detect more and higher order OAMs compared with a discrete metasurface (DM) at the same size, due to its better wavefront sampling capabilities. With the merits of an ultra-compact device size, simple optical structure, and outstanding vortex recognition ability, our approach may underpin the development of integrated optics and quantum systems.

As the ageing population increases, it is essential to manage human resources with residual life prediction, especially for the ageing population. Thus, this study aims to predict residual life using the available information of health statuses, such as the performances in activities of daily living (ADL) and memory. In this study, the principal components of ADL and memory information are extracted for prediction. The relationship between the principal components and residual life is established based on the concept of the proportional residual, which states that the residual life may be proportional to the changes in ADL and memory performance. A recursive model for residual life prediction is formulated and fitted for the Chinese Health and Nutrition Survey data. Finally, a goodness-of-fit test is conducted, and an example case is presented. The results show that the fitted model in this study is more accurate and precise than the original, unfitted model to estimate the residual life of human beings. This study is advantageous over existing studies in two aspects: (1) the model is formulated using a recursive method based on stochastic filtering; (2) the data include both physical status and mental status.

Abstract G protein‐coupled receptor 65 (GPR65), a susceptibility gene for inflammatory bowel diseases (IBD), has been identified to promote Th17 cell pathogenicity and induce T cell apoptosis. However, the potential role of GPR65 in modulating CD4+ T cell immune responses in the pathogenesis of IBD stills not entirely understood. Here, we displayed that GPR65 expression was increased in inflamed intestinal mucosa of IBD patients and positively associated with disease activity. It was expressed in CD4+ T cells and robustly upregulated through the TNF‐α‐caspase 3/8 signalling pathway. Ectopic expression of GPR65 significantly promoted the differentiation of peripheral blood (PB) CD4+ T cells from IBD patients and HC to Th1 and Th17 cells in vitro. Importantly, conditional knockout of Gpr65 in CD4+ T cells ameliorated trinitrobenzene sulfonic acid (TNBS)‐induced acute murine colitis and a chronic colitis in Rag1–/– mice reconstituted with CD45RBhighCD4+ T cells in vivo, characterised by attenuated Th1 and Th17 cell immune response in colon mucosa and decreased infiltration of CD4+ T cells, neutrophils and macrophages. RNA‐seq analysis of Gpr65ΔCD4 and Gpr65flx/flxCD4+ T cells revealed that NUAK family kinase 2 (Nuak2) acts as a functional target of Gpr65 to restrict Th1 and Th17 cell immune response. Mechanistically, GPR65 deficiency promoted NUAK2 expression via the cAMP‐PKA‐C‐Raf‐ERK1/2‐LKB1‐mediated signalling pathway. Consistently, silencing of Nuak2 facilitated the differentiation of Gpr65ΔCD4 and Gpr65flx/flxCD4+ T cells into Th1 and Th17 cells. Therefore, our data point out that GPR65 promotes Th1 and Th17 cell immune response and intestinal mucosal inflammation by suppressing NUAK2 expression, and that targeting GPR65 and NUAK2 in CD4+ T cells may represent a novel therapeutic approach for IBD.

Since the outbreak of novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19), numerous medical staff are fighting on the frontline. However, the possibility of occult infection in medical staff is ignored in many recent studies. Herein, we collected data in a COVID-19 designated hospital from January 22, 2020 to March 10, 2020. A total of 33 medical staff had at least one nucleic acid test of throat swab, immunoglobulin G (IgG) or IgM serum antibody test, and chest computed tomography (CT), were enrolled. Finally, we identified 25 cases (75.8%) were isolated for hospitalized treatment after positive virus detection. In addition, 4 cases who were all negative for nucleic acid test detection with no clinical symptoms, and none of their chest CT were abnormal. However, the results of serum IgG or IgM antibody test in these 4 cases were positive, suggesting the presence of occult infection. In conclusion, data from our single center indicated that SARS-CoV-2 had a high medical infection rate (29/33 = 87.9%) and might have a potential risk of occult infection.

Abstract Background The first few weeks after childbirth are critical, as women may encounter lactation problems and postpartum depression during this period. However, it is still unclear whether early breastfeeding behaviours are related to the symptoms of postnatal depression (PND) in Chinese populations. Therefore, the current study aimed to investigate the association between symptoms of PND and infant feeding practices based on a large-scale Chinese cohort. Methods A prospective study of the community-based cohort was conducted from January 2015 to December 2016. Infant feeding outcomes, including exclusive/partial breastfeeding and formula feeding, were assessed according to the WHO guidelines. Symptoms of PND were assessed by the Edinburgh Postnatal Depression Scale at 4 weeks postpartum. Multivariate generalized estimating equation models were applied to investigate the associations between depressive symptoms and infant feeding behaviours. Results A total of 956 mother-infant pairs were included. Fifty-six mothers presented screen-positive symptoms of PND with a cut-off ≥10. The percentage of early breastfeeding initiation was 75.8%, while the average duration of exclusive breastfeeding was 3.90 ± 2.33 months. Postnatal depressive symptoms were associated with a shorter breastfeeding duration (8.02 vs. 6.32 months, P

Abstract Background Few prospective birth cohort studies are available on the effects of prenatal and early-life exposures on food allergy and eczema among Chinese children. The aim of this study was to evaluate the influence of prenatal and early-life exposures on food allergy and eczema during the first year of life in a prospective birth cohort study. Methods This study was based on a prospective, observational birth cohort of 976 mother-child pairs in three Streets in Changsha, China from January to December 2015. Data on prenatal, early-life exposures and allergic outcomes were obtained from questionnaires collected at birth, and 1, 3, 6, 8, and 12 months of age. Multivariate logistic regression models were performed to estimate the effects of prenatal and early-life exposures on food allergy and eczema. Results Common risk factors for food allergy and eczema in infancy were parental history of allergy, while moderate eggs consumption (3–4 times/week) during pregnancy was protective for both of them compared with low consumption (≤ 2 times/week). Factors only associated with food allergy were maternal aquatic products consumption during pregnancy, number of older siblings and age of solid food introduction, whereas factors only associated with eczema were maternal milk or milk products consumption during pregnancy, maternal antibiotic exposure during pregnancy, season of birth and antibiotic exposure through medication during the first year of life. Conclusion Our study suggests that factors associated with food allergy and eczema are multifaceted, which involving hereditary, environmental and nutritional exposures. Furthermore, differential factors influence the development of food allergy and eczema in infants.

A large number of EGFR mutant non‐small cell lung cancer patients primordially benefit from first‐line treatment with first‐generation EGFR‐tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. However, multiple acquired resistance mechanisms have been described that limit the clinical efficacy of first‐generation EGFR‐TKIs. Herein, we report a rare case of lung adenocarcinoma harboring an EGFR exon 19‐deletion mutation before the administration of target therapy. This patient acquired resistance to first‐generation EGFR‐TKIs through small cell lung cancer (SCLC) transformation accompanied by the T790M mutation. Unexpectedly, this SCLC patient maintained a sensitive response to the third‐generation EGFR‐TKI osimertinib. This special case may indicate that osimertinib represents an effective target drug for SCLC patients who harbor an EGFR T790M mutation.

Objective This study aimed to identify a predictive marker of response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant advanced lung adenocarcinoma. Methods A cohort of 190 patients with EGFR-mutant advanced lung adenocarcinoma was analyzed. Receiver operating characteristic curve analysis was used to evaluate the optimal cutoffs for fibrinogen levels, the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR) for predicting progression-free survival (PFS). Univariate and multivariate survival analyses were performed to identify factors correlated with PFS and overall survival (OS). Results High NLR was associated with worse performance status. In univariate analysis, fibrinogen levels, NLR, and PLR were correlated with OS and PFS. In multivariate analysis, all three variables remained predictive of OS, whereas only fibrinogen levels and PLR were independent prognostic factors for PFS. Furthermore, the combination of fibrinogen levels and PLR (F-PLR score) could stratify patients into three groups with significantly different prognoses, and the score was independently predictive of survival. Conclusion The F-PLR score predicted the prognosis of patients with EGFR-mutant advanced lung adenocarcinoma who received EGFR-TKIs, and this score may serve as a convenient blood-based marker for identifying high-risk patients.

Objectives. This study was designed to explore the intellectual landscape of research into the application of sphingosine 1 phosphate (S1P) in age-related diseases and to identify thematic development trends and research frontiers in this area. Methods. Scientometric research was conducted by analyzing bibliographic records retrieved from the Web of Science (WOS) Sci-Expanded Database dated between 1900 and 2020. Countries, institutions, authors, keyword occurrence analysis, and cooperation network analysis were performed using the CiteSpace and VOSviewer software. Results. A total of 348 valid records were included in the final dataset, and the number of publications and the frequency of citations have grown rapidly over the last ten years. The USA (n=175), China (n=42), and Germany (n=37) were the three largest contributors to the global publications on S1P and aging, while the Medical University of South Carolina (n=15), University of California, San Francisco (n=13), and University of Toronto (n=13) were the leading institutions in this field. Analysis showed that early studies primarily focused on the mechanism of S1P intervention in AD. While S1P and its relevant metabolites have remained a long-term active area of research, recent studies have focused more on interventions aimed at improving retinal degeneration, cardiomyopathy, multiple sclerosis, and diabetes, among others. Conclusions. It is worth mentioning that this manuscript is the first to describe any bibliometric analysis of S1P and its application in age-related interventions. This study includes a discussion of the (1) historical overview of the topic; (2) main contributors: journals, countries, institutes, funding agencies, and authors; (3) collaboration between institutes and authors; (4) research hot spots and zones; and 5) research trends and frontiers. This will enable scholars to understand the current status of S1P research in age-related diseases.

The pathogenesis of type 2 diabetes mellitus (T2DM) is very complicated. The currently well-accepted etiology is the “Ominous Octet” theory proposed by Professor Defronzo. Since presently used drugs for T2DM have limitations and harmful side effects, studies regarding alternative treatments are being conducted. Analyzing the pharmacological mechanism of biomolecules in view of pathogenesis is an effective way to assess new drugs. Sphingosine 1 phosphate (S1P), an endogenous lipid substance in the human body, has attracted increasing attention in the T2DM research field. This article reviews recent study updates of S1P, summarizing its effects on T2DM with respect to pathogenesis, promoting β cell proliferation and inhibiting apoptosis, reducing insulin resistance, protecting the liver and pancreas from lipotoxic damage, improving intestinal incretin effects, lowering basal glucagon levels, etc. With increasing research, S1P may help treat and prevent T2DM in the future.

Chinese cabbage is an important vegetable mainly planted in Asian countries, and mining the molecular mechanism responsible for purple coloration in Brassica crops is fast becoming a research hotspot. In particular, the anthocyanin accumulation characteristic of purple heading Chinese cabbage, along with the plant’s growth and head developing, is still largely unknown. To elucidate the dynamic anthocyanin biosynthesis mechanism of Chinese cabbage during its development processes, here we investigated the expression profiles of 86 anthocyanin biosynthesis genes and corresponding anthocyanin accumulation characteristics of plants as they grew and their heads developed, between purple heading Chinese cabbage 11S91 and its breeding parents. Anthocyanin accumulation of 11S91 increased from the early head formation period onward, whereas the purple trait donor 95T2-5 constantly accumulated anthocyanin throughout its whole plant development. Increasing expression levels of BrMYB2 and BrTT8 together with the downregulation of BrMYBL2.1, BrMYBL2.2, and BrLBD39.1 occurred in both 11S91 and 95T2-5 plants during their growth, accompanied by the significantly continuous upregulation of a phenylpropanoid metabolic gene, BrPAL3.1; a series of early biosynthesis genes, such as BrCHSs, BrCHIs, BrF3Hs, and BrF3’H; as well as some key late biosynthesis genes, such as BrDFR1, BrANS1, BrUF3GT2, BrUF5GT, Br5MAT, and Brp-Cout; in addition to the transport genes BrGST1 and BrGST2. Dynamic expression profiles of these upregulated genes correlated well with the total anthocyanin contents during the processes of plant growth and leaf head development, and results supported by similar evidence for structural genes were also found in the BrMYB2 transgenic Arabidopsis. After intersubspecific hybridization breeding, the purple interior heading leaves of 11S91 inherited the partial purple phenotypes from 95T2-5 while the phenotypes of seedlings and heads were mainly acquired from white 94S17; comparatively in expression patterns of investigated anthocyanin biosynthesis genes, cotyledons of 11S91 might inherit the majority of genetic information from the white type parent, whereas the growth seedlings and developing heading tissues of 11S91 featured expression patterns of these genes more similar to 95T2-5. This comprehensive set of results provides new evidence for a better understanding of the anthocyanin biosynthesis mechanism and future breeding of new purple Brassica vegetables.

Abstract Spoof surface plasmons (SSPs) play crucial roles in terahertz (THz) near‐field photonics. However, both high‐efficiency excitation and wavefront engineering of SSPs remain great challenges, which hinder their wide applications in practice. Here, a scheme is proposed to simultaneously achieve these two goals efficiently using a single ultracompact device. First, it is shown that a gradient meta‐coupler constructed by high‐efficiency Pancharatnam–Berry (PB) meta‐atoms can convert circularly polarized (CP) THz beams into SSPs with absolute efficiency up to 60%. Encoding a parabolic phase profile into the meta‐coupler based on the PB mechanism, it is demonstrated that the device can covert CP beams into SSPs with focusing or defocusing wavefronts, dictated by the chirality of the incident wave. Finally, two distinct chirality‐dependent phase distributions are encoded into the meta‐coupler design by combining the PB and resonance phase mechanisms, and it is demonstrated that the resulting meta‐device can achieve SSP excitations with chirality‐delinked bifunctional wavefront engineering. THz near‐field experiments are performed to characterize all three devices, in excellent agreement with full‐wave simulations. The results pave the road to realize ultracompact devices integrating different functionalities on near‐field manipulations, which can find many applications (e.g., optical sensing, imaging, on‐chip photonics, etc.) in different frequency domains.

Objectives: Accumulating evidence has illustrated greater benefit of immunotherapy in tumors with high tumor mutation burden (TMB), whereas its impact on targeted therapy or chemotherapy is undefined. Herein, we evaluated TMB outside of immuno-oncology in epidermal growth factor receptor (EGFR)–mutant patients and EGFR/ALK wild-type cohorts.Methods: In this retrospective study, we correlated TMB with response rate and progression-free survival (PFS) of patients who received EGFR–tyrosine kinase inhibitors (TKIs) or pemetrexed/platinum as first-line therapy. Tumor mutation burden was evaluated by targeted next-generation sequencing. Patients were divided into low (L)/intermediate (I)/high (H) TMB groups by tertiles.Results: In EGFR-mutant cohort, TMB-L patients had a massively improved PFS compared to TMB-I and TMB-H patients (16.4 vs. 9.0 vs. 7.4 months; log-rank p = 0.006) when treated with first-generation EGFR-TKIs. In EGFR/ALK wild-type cohorts who received pemetrexed/platinum regimen, the objective response rate (ORR) of TMB-L group was statistically superior than that of TMB-I and TMB-H groups (53.8% vs. 23% vs. 8.3%; log-rank p = 0.037), and patients with low TMB had a numerically but not significantly prolonged PFS (6.9 vs. 4.3 vs. 4.6 m; log-rank p = 0.22).Conclusion: Our data provide insights into the relevance between TMB and targeted/chemo therapy. Higher non-synonymous TMB correlates with inferior PFS for first-generation EGFR-TKIs in EGFR-driven patients and worse response to pemetrexed/platinum regimen in EGFR/ALK wild-type patients, which has potential clinical implications for cancer treatment but needs corroboration in larger studies.

Background. Since the end of December 2019, novel coronavirus- (SARS-CoV-2-) infected pneumonia (COVID-19) has spread rapidly in China. The study was designed to describe the clinical characteristics of COVID-19 patients with and without diabetes in Wuhan. Methods. 199 COVID-19 patients were admitted to Wuhan Red Cross Hospital in China from January 24th to March 15th. The cases were divided into the diabetic and nondiabetic groups according to the history of taking antidiabetic drugs or by plasma fasting blood glucose level at admission, and the differences between the groups were compared. A multivariable analysis of independent risk factors for in-hospital death was performed. Results. Among 199 COVID-19 patients, 76 were diabetic and 123 were nondiabetic. Compared with nondiabetics, patients with diabetes were older and had high levels of fasting plasma glucose (FPG), D-dimer, white blood cells, blood urea nitrogen (BUN), and total bilirubin (TBIL) and lower levels of lymphocytes, albumin and oxygen saturation (SaO2), and higher mortality (P

In this paper, an improved channel estimation scheme based on time-domain orthogonal gray complementary training sequence (Golay TS) is proposed to resist subcarrier mutual beat interference in 16-quadrature amplitude modulation multiband orthogonal-frequency-division-multiplexing ultrawide band over fiber (16QAM MB-OFDM UWBoF) systems. The simulation results showed that the performance of system with the improved Golay TS channel estimation scheme was improved by about 1 dB compared with the traditional Golay TS channel estimation scheme, at a bit error rate (BER) of 3.8 × 10−3 after 70 km standard single mode fiber (SSMF) transmission. At the same time, the synchronization and channel estimation performance of Golay TS and the selected frequency-domain orthogonal training sequences (TSs) were compared. The simulation results showed that the performance of system with the TSs channel estimation was improved by about 2.7 dB compared with the improved Golay TS channel estimation.

In this paper, we proposed a coding scheme based on orthogonal cyclic transpose (OCT) precoding combined with low-density parity check (LDPC) code to improve the transmission performance of 128-quadrature amplitude modulation multiband orthogonal-frequency-division-multiplexing ultrawide band over fiber (128 QAM MB-OFDM UWBoF) system. The proposed scheme could not only improve the performance of the system but also average the signal-to-noise ratio (SNR) of subcarriers and reduce the difference among subchannels in practical application. The simulation results showed that compared with the traditional scheme, the receiver performance of this scheme was improved by 2.7 dB when the LDPC-coding rate was 87.5% through 70 km standard single mode fiber (SSMF) transmission and the bit error rate (BER) was 3.8 × 10−3. Besides, the constellation distribution was more convergent and uniform.

Background/Aims: Increasing evidence links microRNAs to the pathogenesis of peripheral vascular disease. We recently found microRNA-125b (miR-125b) to be one of the most significantly down‑regulated microRNAs in human arteries with arteriosclerosis obliterans (ASO) of the lower extremities. However, its function in the process of ASO remains unclear. This study aimed to investigate the expression, regulatory mechanisms, and functions of miR-125b in the process of ASO. Methods: Using the tissue explants adherent method, vascular smooth muscle cells (VSMCs) were prepared for this study. A rat carotid artery balloon injury model was constructed to simulate the development of vascular neointima, and a lentiviral transduction system was used to overexpress serum response factor (SRF) or miR-125b. Quantitative real‑time PCR (qRT‑PCR) was used to detect the expression levels of miR‑125b and SRF mRNA. Western blotting was performed to determine the expression levels of SRF and Ki67. In situ hybridization analysis was used to analyze the location and expression levels of miR-125b. CCK-8 and EdU assays were used to assess cell proliferation, and transwell and wound closure assays were performed to measure cell migration. Flow cytometry was used to evaluate cell apoptosis, and a dual-luciferase reporter assay was conducted to examine the effects of miR‑125b on SRF. Immunohistochemistry and immunofluorescence analyses were performed to analyze the location and expression levels of SRF and Ki67. Results: miR-125b expression was decreased in ASO arteries and platelet-derived growth factor (PDGF)-BB-stimulated VSMCs. miR-125b suppressed VSMC proliferation and migration but promoted VSMC apoptosis. SRF was determined to be a direct target of miR-125b. Exogenous miR-125b expression modulated SRF expression and inhibited vascular neointimal formation in balloon-injured rat carotid arteries. Conclusions: These findings demonstrate a specific role of the miR-125b/SRF pathway in regulating VSMC function and suggest that modulating miR-125b levels might be a novel approach for treating ASO.

Martensite transformation and grain refinement can make austenitic stainless steel stronger, but this comes at a dramatic loss of both ductility and corrosion resistance. Here we report a novel gradient structure in 301 stainless steel sheets, which enables an unprecedented combination of high strength, improved ductility and good corrosion resistance. After producing inter-layer microstructure gradient by surface mechanical attrition treatment, the sheet was annealed at high temperature for a short duration, during which partial reverse transformation occurred to form recrystallized austenitic nano-grains in the surface layer, i.e., introducing extra intra-layer heterogeneity. Such 3D microstructure heterogeneity activates inter-layer and inter-phase interactions during deformation, thereby producing back stress for high yield strength and hetero-deformation induced (HDI) hardening for high ductility. Importantly, the recrystallized austenitic nano-grains significantly ameliorates the corrosion resistance. These findings suggest an effective route for evading the strength–ductility and strength–corrosion tradeoffs in stainless steels simultaneously.

Abstract Efficiently exciting surface plasmon polaritons (SPP) is highly desired in many photonic applications, but most approaches (such as prism and grating couplers) cannot control flexibly their SPP excitation directions. While Pancharatnam-Berry (PB) metasurfaces were recently proposed to achieve direction-controllable SPP excitations, such scheme suffers from low-efficiency issue due to both direct reflections at the coupler surface and the mode mismatch between the coupler and the guiding-out plasmonic structure. In this article, we solve these issues via imposing two criterions to guide design both the metasurface and the plasmonic metal, based on which a direction-controllable SPP excitation with very high efficiency can be realized. As a proof of concept, we designed/fabricated a realistic device working in the microwave regime, and performed both near-field and far-field measurements to demonstrate that it can achieve an spoof SPP conversion efficiency ~78%, much higher than previous devices. Full-wave simulations are in good agreement with experiments, showing that the efficiency can be further pushed to 92% with optimized designs. Our findings can stimulate spoof SPP-related applications, particularly can help enhance the spin-dependent light-matter interactions in low frequency regime.

Abstract Background Postpartum depression causes harm to both mothers and infants. The purpose of this study was to find out several potential risk factors, and to identify the intrinsic interrelationships between factors and postpartum depression by constructing a path model. The results of this study may help to control the increasing incidence of maternal postpartum depression. Methods The study was based on a sample of mothers from a cross-sectional study which was set up at 4 weeks after a mother had childbirth and was conducted in three streets at Kaifu District of Changsha in Hunan province from January to December 2015. Questionnaires were distributed to subjects who responded to questions concerning factors related to pregnancy, delivery and infants within 4 weeks after childbirth. The Edinburgh Postnatal Depression Scale (EPDS) was used to measure postpartum depression. Chi-square test was used to detect significant differences between non-postpartum depression group and postpartum depression group. A path model was constructed to explore the interrelationships between variables, and to verify the relationships between variables and postpartum depression. Results The proportion of maternal postpartum depression was 6.7%. Univariate analysis showed that there were significant differences between non-postpartum depression group and postpartum depression group (all P-values

Metasurfaces, ultrathin metamaterials constructed by planar meta-atoms with tailored electromagnetic (EM) responses, have attracted tremendous attention due to their exotic abilities to freely control EM waves. With active elements incorporated into metasurface designs, one can realize tunable and/or reconfigurable metadevices with functionalities controlled by external stimuli, opening a new platform to dynamically manipulate EM waves. In this article, we briefly review recent progress on tunable/reconfigurable metasurfaces, focusing on their working mechanisms and practical applications. We first describe available approaches, categorized into different classes based on external stimuli applied, to realize homogeneous tunable/reconfigurable metasurfaces, which can offer uniform manipulations on EM waves. We next summarize recent achievements on inhomogeneous tunable/reconfigurable metasurfaces with constitutional meta-atoms locally tuned by external knobs, which can dynamically control the wave-fronts of EM waves. We conclude this review by presenting our own perspectives on possible future directions and existing challenges in this fast developing field.