Communication between the stem cell niche and an adjacent differentiation niche through miRNA and EGFR signaling orchestrates exit from the stem cell state in the Drosophila ovary.

The signaling environment, or niche, often governs the initial difference in behavior of an adult stem cell and a derivative that initiates a path towards differentiation. The transition between an instructive stem cell niche and differentiation niche must generally have single-cell resolution, suggesting that multiple mechanisms might be necessary to sharpen the transition. Here, we examined the Drosophila ovary and found that Cap cells, which are key constituents of the germline stem cell (GSC) niche, express a conserved microRNA (miR-124). Surprisingly, loss of miR-124 activity in Cap cells leads to a defect in differentiation of GSC derivatives. We present evidence that the direct functional target of miR-124 in Cap cells is the epidermal growth factor receptor (EGFR) and that failure to limit EGFR expression leads to the ectopic expression of a key anti-differentiation BMP signal in neighboring somatic escort cells (ECs), which constitute a differentiation niche. We further found that Notch signaling connects EFGR activity in Cap cells to BMP expression in ECs. We deduce that the stem cell niche communicates with the differentiation niche through a mechanism that begins with the selective expression of a specific microRNA and culminates in the suppression of the major anti-differentiation signal in neighboring cells, with the functionally important overall role of sharpening the spatial distinction between self-renewal and differentiation environments.

Tailoring short-chain sulfur molecules to drive redox dynamics for sulfur-based aqueous battery.

Solid-solid reactions stand out in rechargeable sulfur-based batteries due to the robust redox couples and high sulfur utilization in theory. However, conventional solid-solid reactions in sulfur cathode always present slow reaction kinetics and huge redox polarization due to the low electronic conductivity of sulfur and the generation of various electrochemical inert intermediates. In view of this, it is crucial to improve the electrochemical activity of sulfur cathode and tailor the redox direction. Guided by thermodynamics analysis, short-chain sulfur molecules (S2-4) are successfully synthesized by space-limited domain principle. Unlike conventional cyclic S8 molecules with complex routes in solid-solid reaction, short-chain sulfur molecules not only shorten the length of the redox chain but also inhibit the formation of irreversible intermediates, which brings excellent redox dynamics and reversibility. As a result, the Cu-S battery built by short-chain sulfur molecules can deliver a high reversible capacity of 3,133 mAh g-1. To put this into practice, quasi-solid-state aqueous flexible battery based on short-chain sulfur molecules is also designed and evaluated, showing superior mechanical flexibility and electrochemical property. It indicates that the introduction of short-chain sulfur molecules in rechargeable battery can promote the development and application of high-performance sulfur-based aqueous energy storage systems.

Dual synergistic effects assisting Cu-SeS2 electrochemistry for energy storage.

Selenium sulfide (SeS2) features higher electronic conductivity than sulfur and higher theoretical capacity and lower cost than selenium, attracting considerable interest in energy storage field. Although nonaqueous Li/Na/K-SeS2 batteries are attractive for their high energy density, the notorious shuttle effect of polysulfides/polyselenides and the intrinsic limitations of organic electrolyte have hindered the deployment of this technology. To circumvent these issues, here we design an aqueous Cu-SeS2 battery by encapsulating SeS2 in a defect-enriched nitrogen-doped porous carbon monolith. Except the intrinsic synergistic effect between Se and S in SeS2, the porous structure of carbon matrix has sufficient internal voids to buffer the volume change of SeS2 and provides abundant pathways for both electrons and ions. In addition, the synergistic effect of nitrogen doping and topological defect not only enhances the chemical affinity between reactants and carbon matrix but also offers catalytic active sites for electrochemical reactions. Benefiting from these merits, the Cu-SeS2 battery delivers superior initial reversible capacity of 1,905.1 mAh g-1 at 0.2 A g-1 and outstanding long-span cycling performance over 1,000 cycles at 5 A g-1. This work applies variable valence charge carriers to aqueous metal-SeS2 batteries, providing valuable inspiration for the construction of metal-chalcogen batteries.

A triple-synergistic small-molecule sulfur cathode promises energetic Cu-S electrochemistry.

Metal-sulfur batteries have received great attention for electrochemical energy storage due to high theoretical capacity and low cost, but their further development is impeded by low sulfur utilization, poor electrochemical kinetics, and serious shuttle effect of the sulfur cathode. To avoid these problems, herein, a triple-synergistic small-molecule sulfur cathode is designed by employing N, S co-doped hierarchical porous bamboo charcoal as a sulfur host in an aqueous Cu-S battery. Expect the enhanced conductivity and chemisorption induced by N, S synergistic co-doping, the intrinsic synergy of macro-/meso-/microporous triple structure also ensures space-confined small-molecule sulfur as high utilization reactant and effectively alleviates the volume expansion during conversion reaction. Under a further joint synergy between hierarchical structure and heteroatom doping, the resulting sulfur cathode endows the Cu-S battery with outstanding electrochemical performance. Cycled at 5 A g-1, it can deliver a high reversible capacity of 2,509.8 mAh g-1 with a good capacity retention of 97.9% after 800 cycles. In addition, a flexible hybrid pouch cell built by a small-molecule sulfur cathode, Zn anode, and gel electrolytes can firmly deliver high average operating voltage of about 1.3 V with a reversible capacity of over 2,500 mAh g-1 under various destructive conditions, suggesting that the triple-synergistic small-molecule sulfur cathode promises energetic metal-sulfur batteries.

Metabolic Syndrome and Risk of Amyotrophic Lateral Sclerosis: Insights from a Large-Scale Prospective Study.

OBJECTIVE: Although metabolic abnormalities are implicated in the etiology of neurodegenerative diseases, their role in the development of amyotrophic lateral sclerosis (ALS) remains a subject of controversy. We aimed to identify the association between metabolic syndrome (MetS) and the risk of ALS. METHODS: This study included 395,987 participants from the UK Biobank to investigate the relationship between MetS and ALS. Cox regression model was used to estimate hazard ratios (HR). Stratified analyses were performed based on gender, body mass index (BMI), smoking status, and education level. Mediation analysis was conducted to explore potential mechanisms. RESULTS: In this study, a total of 539 cases of ALS were recorded after a median follow-up of 13.7 years. Patients with MetS (defined harmonized) had a higher risk of developing ALS after adjusting for confounding factors (HR: 1.50, 95% CI: 1.19-1.89). Specifically, hypertension and high triglycerides were linked to a higher risk of ALS (HR: 1.53, 95% CI: 1.19-1.95; HR: 1.31, 95% CI: 1.06-1.61, respectively). Moreover, the quantity of metabolic abnormalities showed significant results. Stratified analysis revealed that these associations are particularly significant in individuals with a BMI <25. These findings remained stable after sensitivity analysis. Notably, mediation analysis identified potential metabolites and metabolomic mediators, including alkaline phosphatase, cystatin C, γ-glutamyl transferase, saturated fatty acids to total fatty acids percentage, and omega-6 fatty acids to omega-3 fatty acids ratio. INTERPRETATION: MetS exhibits a robust association with an increased susceptibility to ALS, particularly in individuals with a lower BMI. Furthermore, metabolites and metabolomics, as potential mediators, provide invaluable insights into the intricate biological mechanisms. ANN NEUROL 2024.

Creation of Room-Temperature Sub-100 nm Antiferromagnetic Skyrmions in an Antiferromagnet IrMn through Interfacial Exchange Coupling.

Antiferromagnetic (AFM) skyrmions are magnetic vortices composed of antiparallell-aligned neighboring spins. In stark contrast to conventional skyrmions based on ferromagnetic order, AFM skyrmions have vanished stray fields, higher response frequencies, and rectified translational motion driven by an external force. Therefore, AFM skyrmions promise highly efficient spintronics devices with high bit mobility and density. Nevertheless, the experimental realization of intrinsic AFM skyrmions remains elusive. Here, we show that AFM skyrmions can be nucleated via interfacial exchange coupling at the surface of a room-temperature AFM material, IrMn, exploiting the particular response from uncompensated moments to the thermal annealing and imprinting effects. Further systematic magnetic characterizations validate the existence of such an AFM order at the IrMn/CoFeB interfaces. Such AFM skyrmions have a typical size of 100 nm, which presents pronounced robustness against field and temperature. Our work opens new pathways for magnetic topological devices based on AFM skyrmions.

Colossal Ferroelectric Photovoltaic Effect in Inequivalent Double-Perovskite Bi2FeMnO6 Thin Films.

Double perovskite films have been extensively studied for ferroelectric order, ferromagnetic order, and photovoltaic effects. The customized ion combinations and ordered ionic arrangements provide unique opportunities for bandgap engineering. Here, a synergistic strategy to induce chemical strain and charge compensation through inequivalent element substitution is proposed. A-site substitution of the barium ion is used to modify the chemical valence and defect density of the two B-site elements in Bi2FeMnO6 double perovskite epitaxial thin films. We dramatically increased the ferroelectric photovoltaic effect to ∼135.67 µA/cm2 from 30.62 µA/cm2, which is the highest in ferroelectric thin films with a thickness of less than 100 nm under white-light LED irradiation. More importantly, the ferroelectric polarization can effectively improve the photovoltaic efficiency of more than 5 times. High-resolution HAADF-STEM, synchrotron-based X-ray diffraction and absorption spectroscopy, and DFT calculations collectively demonstrate that inequivalent ion plays a dual role of chemical strain (+1.92 and -1.04 GPa) and charge balance, thereby introducing lattice distortion effects. The reduction of the oxygen vacancy density and the competing Jahn-Teller distortion of the oxygen octahedron are the main phenomena of the change in electron-orbital hybridization, which also leads to enhanced ferroelectric polarization values and optical absorption. The inequivalent strategy can be extended to other double perovskite systems and applied to other functional materials, such as photocatalysis for efficient defect control.

Adaptive-memory-length look-up table (LUT)-based digital pre-distortion for IM/DD underwater wireless optical communications.

A digital pre-distortion (DPD) scheme based on an adaptive-memory-length look-up table (AML-LUT) is proposed and experimentally demonstrated in a four-level pulse amplitude modulation (4-PAM) underwater optical wireless communication (UOWC) system. By implementing adaptive memory length for each pattern in the AML-LUT-based DPD, the size of the AML-LUT can be significantly reduced without sacrificing performance compared to both the full-size LUT and the multi-symbol simplified look-up table (MSS-LUT)-based DPDs. The performance of the proposed AML-LUT-based DPD is experimentally evaluated for a 625 Mbit/s 4-PAM UOWC over 1 m transmission length. Experimental results show that compared with the full-size LUT with a memory length of 7 (LUT-7)-based DPD, the proposed AML-LUT-based DPD (i) incurs a marginal power penalty of 0.5 dB at both the 7% hard-decision forward error correction (HD-FEC) and KP4-FEC threshold limits, while simultaneously reducing the implementation complexity (i.e., the LUT size) by 93%; (ii) achieves comparable transmission performance compared to the MSS-LUT-based DPD, while reducing the implementation complexity by 89%; and (iii) shows great potential for high-speed, low-complexity and memory-efficient intensity modulation and direct detection (IM/DD) UOWC and short-reach optical interconnects.

Melatonin attenuates diabetic cardiomyopathy by increasing autophagy of cardiomyocytes via regulation of VEGF-B/GRP78/PERK signaling pathway.

AIMS: Diabetic cardiomyopathy (DCM) is a major cause of mortality in patients with diabetes, and the potential strategies for treating DCM are insufficient. Melatonin (Mel) has been shown to attenuate DCM, however, the underlying mechanism remains unclear. The role of vascular endothelial growth factor-B (VEGF-B) in DCM is little known. In present study, we aimed to investigate whether Mel alleviated DCM via regulation of VEGF-B and explored its underlying mechanisms. METHODS AND RESULTS: We found that Mel significantly alleviated cardiac dysfunction and improved autophagy of cardiomyocytes in type 1 diabetes mellitus (T1DM) induced cardiomyopathy mice. VEGF-B was highly expressed in DCM mice in comparison with normal mice, and its expression was markedly reduced after Mel treatment. Mel treatment diminished the interaction of VEGF-B and Glucose-regulated protein 78 (GRP78) and reduced the interaction of GRP78 and protein kinase RNA -like ER kinase (PERK). Furthermore, Mel increased phosphorylation of PERK and eIF2α, then up-regulated the expression of ATF4. VEGF-B-/- mice imitated the effect of Mel on wild type diabetic mice. Interestingly, injection with Recombinant adeno-associated virus serotype 9 (AAV9)-VEGF-B or administration of GSK2656157 (GSK), an inhibitor of phosphorylated PERK abolished the protective effect of Mel on DCM. Furthermore, rapamycin, an autophagy agonist displayed similar effect with Mel treatment; while 3-Methyladenine (3-MA), an autophagy inhibitor neutralized the effect of Mel on high glucose-treated neonatal rat ventricular myocytes. CONCLUSIONS: These results demonstrated that Mel attenuated DCM via increasing autophagy of cardiomyocytes, and this cardio-protective effect of Mel was dependent on VEGF-B/GRP78/PERK signaling pathway.

Immune and regulative characterization of complement-related gene cfhl5 in response to Vibrio harveyi challenge in Cynoglossus semilaevis.

Complement factor H-related protein (CFHR) plays an important role in regulating complement activation and defensive responses. The function of CFHR2 (complement factor H related 2), a member of the CFHR family, in fish remains unclear. Here, we report the genetic relationship, expression characteristics and regulatory mechanism of cfhl5 (complement factor H like 5) gene, which encodes CFHR2 in Chinese tongue sole. We observed that the cfhl5 gene was widely expressed in several tissues, such as brain, heart and immune organs, and was most abundantly expressed in liver. After injection with Vibrio harveyi, the expression of cfhl5 was up-regulated significantly in liver, spleen and kidney at 12 or 24 hours post infection (hpi), suggesting an involvement of this gene in the acute immune response. Knockdown of cfhl5 in liver cells significantly up-regulated the expression of the pro-inflammatory cytokines tnf-α (tumor necrosis factor-alpha) and il1ß (interleukin-1beta), the immunomodulatory factor il10 (interleukin-10) and the lectin complement pathway gene masp1 (MBL-associated serine protease 1), and down-regulated the expression of complement components c3 (complement 3) and cfi (complement factor I). In our previous work, we found that cfhl5 gene was significantly higher methylated and lower expressed in the resistant family compared with the susceptible family. Therefore, we used dual-luciferase reporter system to determine the effect of DNA methylation on this gene and found that DNA methylation could inhibit the promoter activity to reduce its expression. These results demonstrated that the expression of cfhl5 is regulated by DNA methylation, and this gene might play an important role in the immune response by regulating the expression of cytokines and complement components genes in Chinese tongue sole.

High-Quality TiO2 Electron Transport Film Prepared via Vacuum Ultraviolet Illumination for MAPbI3 Perovskite Solar Cells.

The electron transport layer (ETL) plays an important role in determining the conversion efficiency and stability of perovskite solar cells (PSCs). Here, TiO2 thin film was prepared by irradiating diisopropoxy diacetylacetone titanium precursor thin film with 172 nm vacuum ultraviolet (VUV) at a low temperature. The prepared TiO2 thin film has higher electron mobility and conductivity. As it is used as an ETL for MAPbI3 PSCs, its band structure is better matched with the perovskite, and at the same time, due to the good interface contact, more uniform perovskite crystals are formed. Most importantly, a large number of hydroxyl radicals were formed during VUV irradiation of the precursor film, which made up for the oxygen defect present on the surface of the TiO2 thin film, and were adsorbed to the film surface. These hydroxyl groups form hydrogen bonds with methylammonium (MA) components on the MAPbI3 buried surface, thus promoting the transfer of photogenerated electrons at the MAPbI3/ETL interface. The power conversion efficiency of PSCs fabricated in air with the ETL prepared by VUV irradiation is 20.46%, which is higher than that of the contrast solar cell based on the sintered ETL (17.96%).

Motoric Cognitive Risk Syndrome as a Predictor of Adverse Health Outcomes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Motoric cognitive risk syndrome (MCR) is a newly proposed pre-dementia syndrome characterized by subjective cognitive complaints (SCCs) and slow gait (SG). Increasing evidence links MCR to several adverse health outcomes, but the specific relationship between MCR and the risk of frailty, Alzheimer's disease (AD), and vascular dementia (VaD) remains unclear. Additionally, literature lacks analysis of MCR's components and associated health outcomes, complicating risk identification. This systematic review and meta-analysis aimed to provide a comprehensive overview of MCR's predictive value for adverse health outcomes. METHODS: Relevant cross-sectional, cohort, and longitudinal studies examining the association between MCR and adverse health outcomes were extracted from ten electronic databases. The Newcastle-Ottawa Scale (NOS) and modified NOS were used to assess the risk of bias in studies included in the analysis. Relative ratios (RRs) and 95% confidence intervals (CIs) were pooled for outcomes associated with MCR. RESULTS: Twenty-eight longitudinal or cohort studies and four cross-sectional studies with 1,224,569 participants were included in the final analysis. The risk of bias in all included studies was rated as low or moderate. Pooled analysis of RR indicated that MCR had a greater probability of increased the risk of dementia (adjusted RR = 2.02; 95% CI = 1.94-2.11), cognitive impairment (adjusted RR = 1.72; 95% CI = 1.49-1.99), falls (adjusted RR = 1.32; 95% CI = 1.17-1.50), mortality (adjusted RR = 1.66; 95% CI = 1.32-2.10), and hospitalization (adjusted RR = 1.46; 95% CI = 1.16-1.84); MCR had more prominent predictive efficacy for AD (adjusted RR = 2.23; 95% CI = 1.81-2.76) compared to VaD (adjusted RR = 3.78; 95% CI = 0.49-28.95), while excluding analyses from the study that utilized the timed-up-and-go test and one-leg-standing to evaluate gait speed. One study examined the association between MCR and disability (hazard ratios [HR] = 1.69; 95% CI = 1.08-2.02) and frailty (OR = 5.53; 95% CI = 1.46-20.89). SG was a stronger predictor of the risk for dementia and falls than SCC (adjusted RR = 1.22; 95% CI = 1.11-1.34 vs. adjusted RR = 1.19; 95% CI = 1.03-1.38). CONCLUSION: MCR increases the risk of developing any discussed adverse health outcomes, and the predictive value for AD is superior to VaD. Additionally, SG is a stronger predictor of dementia and falls than SCC. Therefore, MCR should be routinely assessed among adults to prevent poor prognosis and provide evidence to support future targeted interventions.

Half-spectrum OFDM to quadruple the spectral efficiency of underwater wireless optical communication with digital power division multiplexing.

Improving the spectrum efficiency (SE) is an effective method to further enhance the data rate of bandwidth-limited underwater wireless optical communication (UWOC) systems. Non-orthogonal frequency-division multiplexing (NOFDM) with a compression factor of 0.5 can save half of the bandwidth without introducing any inter-carrier-interference (ICI) only if the total number of subcarriers is large enough, and we termed it as half-spectrum OFDM (HS-OFDM). To the best of our knowledge, this is the first reported work on a closed-form HS-OFDM signal in the discrete domain from the perspective of a correlation matrix. Due to the special mathematical property, no extra complex decoding algorithm is required at the HS-OFDM receiver, making it as simple as the conventional OFDM receiver. Compared with traditional OFDM, HS-OFDM can realize the same data rate, but with a larger signal-to-noise ratio (SNR) margin. To fully use the SNR resource of the communication system, we further propose a digital power division multiplexed HS-OFDM (DPDM-HS-OFDM) scheme to quadruple the SE of conventional OFDM for the bandwidth-starved UWOCs. The experimental results show that HS-OFDM can improve the receiver sensitivity by around 4 dB as opposed to conventional 4QAM-OFDM with the same data rate and SE. With the help of the DPDM-HS-OFDM scheme, the data rate of multi-user UWOC can reach up to 4.5 Gbps under the hard-decision forward error correction (HD-FEC) limit of a bit error rate (BER) of 3.8×10-3. Although there is some performance degradation in comparison with single-user HS-OFDM, the BER performance of multi-user DPDM-HS-OFDM is still superior to that of conventional single-user 4QAM-OFDM. Both single-user HS-OFDM and multi-user DPDM-HS-OFDM successfully achieve 2 Gbps/75 m data transmission, indicating that the DPDM-HS-OFDM scheme is of great importance in bandwidth-limited UWOC systems and has guiding significance to underwater wireless optical multiple access.

Effect of mixed fermentation of Lactiplantibacillus plantarum and Lactiplantibacillus pentosus on phytochemical and flavor characteristics of Wallace melon juice.

BACKGROUND: Melons (Cucumis melo L.) are among the most commonly consumed fruits but they are highly susceptible to mechanical damage and rot during storage and transportation. New processed products are needed to avoid postharvest fruit loss and to increase health benefits. Fermentation is an effective means of utilizing the nutrients and improving flavor. RESULTS: Fermented melon juice (MJ) was prepared using three potential probiotics Lactiplantibacillus plantarum CICC21824 (LP), Lactiplantibacillus plantarum GB3-2 (LG), and Lactiplantibacillus pentosus XZ-34 (LX). The nutrition, flavor characteristics, and digestive properties of different fermented MJs were compared. The results demonstrated that, in comparison with mono-fermentation, mixed fermentation by LG and LX could increase the level of organic acids and phenolic acids. Correspondingly, antioxidant capacity was improved significantly and positively correlated with p-coumaric acid and cinnamic acid content. The production of alcohols and acids was more strongly enhanced by mixed culture fermentation, whereas mono-fermentation reduced the content of esters, especially ethyl acetate and isopropyl acetate. Aldehydes and ketones increased significantly in fermented MJ, and damascenone and heptanal could be the characteristic aroma compounds. CONCLUSION: Mixed fermented MJ provides more beneficial phytochemicals, better flavor, and stronger antioxidant properties than mono-fermentation. © 2024 Society of Chemical Industry.

Structure and Defect Engineering Synergistically Boost High Solar-to-Chemical Conversion Efficiency of Cerium oxide/Au Hollow Nanomushrooms for Nitrogen Photofixation.

Photocatalytic nitrogen fixation using solar illumination under ambient conditions is a promising strategy for production of the indispensable chemical NH3 . However, due to the catalyst's limitations in solar energy utilization, loss of hot electrons during transfer, and low nitrogen adsorption and activation capacity, the unsatisfactory solar-to-chemical conversion (SCC) efficiencies of most photocatalysts limit their practical applications. Herein, cerium oxide nanosheets with abundant strain-VO defects were anchored on Au hollow nanomushroom through atomically sharp interfaces to construct a novel semiconductor/plasmonic metal hollow nanomushroom-like heterostructure (denoted cerium oxide-AD/Au). Plasmonic Au extended the absorption of light from the visible to the second near-infrared region. The superior interface greatly enhanced the transfer efficiency of hot electrons. Abundant strain-VO defects induced by interfacial compressive strain promoted adsorption and in situ activation of nitrogen, and such synergistic promotion of strain and VO defects was further confirmed by density functional theory calculations. The judicious structural and defect engineering co-promoted the efficient nitrogen photofixation of the cerium oxide-AD/Au heterostructures with a SCC efficiency of 0.1 % under simulated AM 1.5G solar illumination, which is comparable to the average solar-to-biomass conversion efficiency of natural photosynthesis by typical plants, thus exhibiting significant potential as a new candidate for artificial photosynthesis.

Effectiveness and safety of radiotherapy plus programmed death-1 inhibitors and lenvatinib in patients with advanced biliary tract carcinoma: a real-world study.

BACKGROUND: Radiotherapy (RT) may function synergistically with immunotherapy and targeted agents (TA). This study aimed to assess the effectiveness and safety of RT combined with programmed death-1 (PD-1) inhibitors and lenvatinib in patients with relapsed or refractory advanced biliary tract carcinoma (BTC). METHODS: This retrospective study included patients with relapsed or refractory advanced BTC who received RT combined with PD-1 inhibitors and lenvatinib at the Peking Union Medical College Hospital (PUMCH). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. RESULTS: Thirty-one patients who received RT combined with PD-1 inhibitors and lenvatinib as a second- or later-line therapy were analyzed. RT sites were mainly distributed in the liver lesions (64.5%) and lymph nodes (58.1%). The ORR and DCR were 32.3% (10/31; 95% CI: 14.8-49.7) and 87.1% (27/31; 95% CI: 74.6-99.6), respectively. The median PFS (mPFS) and median OS (mOS) were 7.9 (95% CI: 7.1-8.7) and 11.7 (95% CI: 8.3-15.0) months, respectively. Subgroup analyses of this cohort included 12 and 19 patients who received concurrent and salvage (> 6 weeks after commencing PD-1 inhibitor therapy) RT, respectively. The salvage RT group had higher mOS (11.7 vs. 10.5; p = 0.75) and mPFS (7.9 vs. 6.9; p = 0.85) than the concurrent RT group; however, statistical significance was not reached. All patients experienced any-grade adverse events (AEs), and excessive PD-1 inhibitors or RT toxicity were not observed. CONCLUSIONS: RT, PD-1 inhibitors, and lenvatinib may be safely combined and have antitumor effectiveness in patients with advanced BTC.

Wafer-scale single-crystal monolayer graphene grown on sapphire substrate.

The growth of inch-scale high-quality graphene on insulating substrates is desirable for electronic and optoelectronic applications, but remains challenging due to the lack of metal catalysis. Here we demonstrate the wafer-scale synthesis of adlayer-free ultra-flat single-crystal monolayer graphene on sapphire substrates. We converted polycrystalline Cu foil placed on Al2O3(0001) into single-crystal Cu(111) film via annealing, and then achieved epitaxial growth of graphene at the interface between Cu(111) and Al2O3(0001) by multi-cycle plasma etching-assisted-chemical vapour deposition. Immersion in liquid nitrogen followed by rapid heating causes the Cu(111) film to bulge and peel off easily, while the graphene film remains on the sapphire substrate without degradation. Field-effect transistors fabricated on as-grown graphene exhibited good electronic transport properties with high carrier mobilities. This work breaks a bottleneck of synthesizing wafer-scale single-crystal monolayer graphene on insulating substrates and could contribute to next-generation graphene-based nanodevices.

Low-complexity frequency-domain nonlinear equalizer with absolute operation for underwater wireless optical communications.

A low-complexity 3rd-order frequency-domain nonlinear equalizer (FD-NLE) with absolute operation is proposed and experimentally demonstrated for underwater wireless optical communications (UWOC). In the proposed FD-NLE scheme, absolute operation and fast Fourier transform (FFT) with multiplication operations are utilized instead of the square and convolution operations used in conventional polynomial nonlinear equalizers (PNLEs), respectively. Therefore, complexity reductions by over 77.3% and 66.9% can be achieved compared with those of PNLE and PNLE with absolute operation, respectively, with a memory length larger than 8. A UWOC system using orthogonal frequency division multiplexing (OFDM) signals with adaptive bit and power loading is also demonstrated to evaluate the performance of the proposed scheme. Experimental results show that data rate increments by ∼ 5.6% and ∼ 5.7% at BER below 7% hard-decision forward error correction (HD-FEC) limit of 3.8 × 10-3, compared with PNLE and PNLE with absolute operation, respectively, are realized using the proposed scheme. Meanwhile, the proposed scheme has an up to 14.7% complexity reduction compared with conventional frequency-domain PNLE (FD-PNLE), while maintaining similar equalization performance.

C-band 100-GBaud PS-PAM-4 transmission over 50-km SSMF enabled by FIR-filter-based pre-electronic dispersion compensation.

Chromatic dispersion (CD) is always an obstacle to C-band high-speed intensity modulation and direct detection (IM/DD) transmissions, especially with a fiber reach of > 20 km. To reach beyond net-100-Gb/s IM/DD transmission over 50-km standard single mode fiber (SSMF), we for the first time present a CD-aware probabilistically shaped four-ary pulse amplitude modulation (PS-PAM-4) signal transmission scheme with a FIR-filter-based pre-electronic dispersion compensation (FIR-EDC) for C-band IM/DD transmission system. With the help of the FIR-EDC at the transmitter, 100-GBaud PS-PAM-4 signal transmission at 150-Gb/s line rate and 115.2-Gb/s net rate over 50-km SSMF is realized with only feed-forward equalization (FFE) at the receiver side. The superiority of the CD-aware PS-PAM-4 signal transmission scheme over other benchmark schemes has been successfully verified by experiments. Experimental results show that 24.5% improvement of system capacity is obtained by the FIR-EDC-based PS-PAM-4 signal transmission scheme in comparison to the FIR-EDC-based on-off keying (OOK) signal transmission scheme. Compared with the FIR-EDC-based uniform PAM-4 signal transmission scheme or the PS-PAM-4 signal transmission scheme without EDC, the capacity improvement obtained by the FIR-EDC-based PS-PAM-4 signal transmission scheme becomes more profound. The results show the potential and feasibility of such CD-aware PS-PAM-4 signal transmission scheme applied in CD-constrained IM/DD datacenter interconnects.

Theoretical investigations of weakly- and strongly-coupled multi-core fibers for the applications of optical submarine communications under power and fiber count limits.

The practical cable design for optical submarine communications has a limited fiber pair count due to the mechanical considerations of cable weight and size. Consequently, multi-core fibers (MCFs) could exhibit higher capacity than conventional single-mode fibers (SMFs) thanks to space division multiplexing (SDM). That is because the power supply to a submarine cable is fed by the voltage difference between shores. Under the power-limited condition, SDM improves the cable capacity by using more paths which outperforms the SMF link whose capacity approximately complies with a logarithmic relationship to optical power. At the same time, fiber nonlinearity can be alleviated by the reduced power density of transmitted light in MCFs, due to the increased spatial diversity and mode coupling among coupled cores. In this work, we theoretically investigate the potentials of MCFs including weakly-coupled multicore fiber (WC-MCF) and strongly-coupled multicore fiber (SC-MCF) as the propagation media for submarine communications across the Atlantic and the Pacific. To fairly compare the performances of SMFs- and MCFs-based submarine cables, the Gaussian noise (GN) model for SDM links is employed to optimize the systematic settings including spatial multiplicity and single span length. Then, we develop an SDM and wavelength division multiplexing (WDM) fiber transmission model based on coupled nonlinear Schrodinger equations (CNSE) to investigate the optical filed coupling effect in MCFs-based cables. The developed transmission model has been self-examined by measuring the inter-core crosstalk (IC-XT) and spatial mode dispersion (SMD), referring to the set values. As indicated by the theoretical analysis, the WC-MCFs cable exhibits a larger capacity than the SMFs cable, when the fiber pair count is limited below 32. Moreover, the SC-MCFs cable outperforms the WC-MCFs cable thanks to the reduced fiber nonlinearity due to the random mode coupling and the assistance of multiple-input and multiple-output digital signal processing (MIMO-DSP). At last, the marginal influences of IC-XT, SMD, and insertion loss of Fan-in and Fan-out couplers are also analyzed for the MCFs cable.