A Universal Approach to Determine the Atomic Layer Numbers in Two-Dimensional Materials Using Dark-Field Optical Contrast.

Two-dimensional (2D) materials possess unique properties primarily due to the quantum confinement effect, which highly depends on their thicknesses. Identifying the number of atomic layers in these materials is a crucial, yet challenging step. However, the commonly used optical reflection method offers only very low contrast. Here, we develop an approach that shows unprecedented sensitivity by analyzing the brightness of dark-field optical images. The brightness of the 2D material edges has a linear dependence on the number of atomic layers. The findings are modeled by Rayleigh scattering, and the results agree well with the experiments. The relative contrast of single-layer graphene can reach 70% under white-light incident conditions. Furthermore, different 2D materials were successfully tested. By adjusting the exposure conditions, we can identify the number of atomic layers ranging from 1 to over 100. Finally, this approach can be applied to various substrates, even transparent ones, making it highly versatile.

Flexible Liquid Crystal Polymer Technologies from Microwave to Terahertz Frequencies.

With the emergence of fifth-generation (5G) cellular networks, millimeter-wave (mmW) and terahertz (THz) frequencies have attracted ever-growing interest for advanced wireless applications. The traditional printed circuit board materials have become uncompetitive at such high frequencies due to their high dielectric loss and large water absorption rates. As a promising high-frequency alternative, liquid crystal polymers (LCPs) have been widely investigated for use in circuit devices, chip integration, and module packaging over the last decade due to their low loss tangent up to 1.8 THz and good hermeticity. The previous review articles have summarized the chemical properties of LCP films, flexible LCP antennas, and LCP-based antenna-in-package and system-in-package technologies for 5G applications, although these articles did not discuss synthetic LCP technologies. In addition to wireless applications, the attractive mechanical, chemical, and thermal properties of LCP films enable interesting applications in micro-electro-mechanical systems (MEMS), biomedical electronics, and microfluidics, which have not been summarized to date. Here, a comprehensive review of flexible LCP technologies covering electric circuits, antennas, integration and packaging technologies, front-end modules, MEMS, biomedical devices, and microfluidics from microwave to THz frequencies is presented for the first time, which gives a broad introduction for those outside or just entering the field and provides perspective and breadth for those who are well established in the field.

A comprehensive analysis of the MAGE family as prognostic and diagnostic markers for hepatocellular carcinoma.

The Melanoma Antigen Gene (MAGE) family is a large, highly conserved group of proteins which was reported to participate in the progression of multiple cancers in humans. However, the function of distinct MAGE genes in hepatocellular carcinoma (HCC) is largely unclear. In this study, we comprehensively evaluated the expression, clinical significance, genetic alteration, interaction network and functional enrichment of MAGEs in HCC. Our research showed that many MAGE genes were dysregulated in HCC. Among them, MAGEA1, MAGEC2, MAGED1, MAGED2, MAGEF1 and MAGEL2 were significantly associated with clinical stage and differentiation of HCC. MAGED1, MAGED2, MAGEA6, MAGEA12, MAGEA10, MAGEB4, MAGEL2 and MAGEC3 significantly correlated with HCC prognosis. Further functional enrichment analysis suggested the dysregulated MAGEs may play important roles in signal transduction. These results indicate that multiple dysregulated MAGEs might play important roles in the development of HCC and can be exploited as useful biomarkers for diagnosis and treatment in HCC.

Continuous veno-venous hemofiltration with oXiris hemofilters for the treatment of Fournier's gangrene: A case report series.

Background: Fournier's gangrene (FG) is a severe form of necrotizing fasciitis primarily caused by gram-negative bacteria. FG can rapidly progress to septic shock, resulting in high mortality rates. In the past, the management of the inflammatory response caused by gram-negative bacteria has been limited. Continuous Veno-Venous Hemofiltration with oXiris hemofilters (oXiris-CVVH) has shown promise in adsorbing inflammatory factors and endotoxins, making it an attractive approach for treating FG. This study aims to provide insights into the characteristics of patients with FG and septic shock who have been successfully treated using oXiris-CVVH, based on a series of patient cases. Results: This study presents the management of 4 cases in the intensive care units of a tertiary hospital in southern China. The use of oXiris-CVVH in patients with septic shock and FG yielded valuable practical insights. Conclusion: Based on the experience gained from these 4 cases, the utilization of oXiris-CVVH demonstrated potential in reducing the Sequential Organ Failure Assessment (SOFA) score, improving prognosis, and effectively lowering the levels of lactic acid and procalcitonin (PCT) in the blood. Additionally, it facilitated a reduction in the dosage of noradrenaline. Therefore, oXiris-CVVH should be considered as an adjunctive therapy in the treatment of patients with FG and septic shock.

Evaluation of the efficacy and safety of first- and second-line immunotherapy in patients with metastatic colorectal cancer: a systematic review and network meta-analysis based on randomized controlled trials.

Background: A multitude of randomized controlled trials (RCTs) conducted in both the initial and subsequent treatment settings for patients diagnosed with metastatic colorectal cancer (mCRC) have provided clinical evidence supporting the efficacy of immunotherapy with the use of immune checkpoint inhibitors (ICIs). In light of these findings, the U.S. Food and Drug Administration (FDA) has authorized the use of several ICIs in specific subpopulations of mCRC patients. Nevertheless, there remains a dearth of direct comparative RCTs evaluating various treatment options. Consequently, the most effective ICI therapeutic strategy for microsatellite-stable (MSS) subgroup and microsatellite instability (MSI) subgroup in the first- and second-line therapies remains undefined. To address this gap, the present study employs a Bayesian network meta-analysis to ascertain the most effective first- and second-line ICI therapeutic strategies. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, with the retrieval date ranging from the databases' inception to August 20, 2024. A total of 875 studies were identified, and seven were ultimately included in the analysis after a screening process. A systematic review and network meta-analysis were conducted on the basis of the search results. Results: This comprehensive analysis, comprising seven RCTs, evaluated first-line and second-line immunotherapy regimens in 1,358 patients diagnosed with mCRC. The treatments under investigation consisted of five initial treatments, including three focusing on MSS patients and two on MSI patients, as well as two secondary immunotherapy regimens, both focusing on MSS patients. A total of 1051 individuals underwent first-line treatment, while 307 received second-line treatment. The application of ICIs proved to offer varying degrees clinical benefits when compared to standard-of-care therapy alone, both in two subgroups of the first and the second treatment phases. Of particular note is the performance of Nivolumab combination with ipilimumab, which demonstrated superior efficacy in improving progression-free survival (PFS) (HR=0.21; 95% CI, 0.13-0.34),. Moreover, the treatment demonstrated an optimal safety profile, with a relatively low risk of adverse events (OR = 0.33; 95% CI, 0.19-0.56), compared to other first-line treatment modalities for MSI subgroup. Regarding MSS subgroup, the improvement of PFS by Nivolumab plus standard-of-care (SOC) was relatively significant (HR = 0.74; 95% CI, 0.53-1.02). In the realm of second-line therapies for MSS subgroup, the administration of Atezolizumab plus SOC has proven to be an effective approach for prolonging PFS, exhibiting an HR of 0.66 (95% CI, 0.44-0.99). These findings underscore the clinical benefits and safety profiles of ICIs in the treatment of mCRC across various treatment lines. Conclusions: The clinical application of ICIs in both first- and second-line treatment strategies for patients with mCRC yields substantial therapeutic benefits. A detailed assessment in this study indicates that first-line treatment with Nivolumab combination with ipilimumab may represent an efficacious and well-tolerated therapeutic approach for MSI subgroup. In terms of MSS subgroup in first-line therapy, Nivolumab plus SOC may be a relative superior choice. In the context of second-line therapy for MSS subgroup, it is evident that a combination of Atezolizumab and SOC represents a preferable option for enhancing PFS. Furthermore, it is noteworthy that other ICIs treatment regimens also exhibit great value in various aspects, with the potential to inform the development of future clinical treatment guidelines and provide a stronger rationale for the selection of ICIs in both first- and second-line therapeutic strategies for mCRC. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024543400.

Seasonal Dynamics of Eukaryotic Microbial Communities in the Water-Receiving Reservoir of the Long-Distance Water Diversion Project, China.

Inter-basin water transfer projects, such as the Yellow River to Qingdao Water Diversion Project (YQWD), are essential for addressing water scarcity, but impact local aquatic ecosystems. This study investigates the seasonal characteristics of eukaryotic microbial communities in the Jihongtan Reservoir, the main water-receiving body of YQWD, over a one-year period using 18S rDNA amplicon sequencing. The results showed that the eukaryotic microbial diversity did not exhibit significant seasonal variation (p > 0.05), but there was a notable variance in the community structure (p < 0.05). Arthropoda and Paracyclopina, representing the most dominant phylum and the most dominant genus, respectively, both exhibited the lowest abundance during the winter. The Chlorophyta, as the second-dominant phylum, demonstrates its higher abundance in the spring and winter. The Mantel test and PLS-PM (Partial Least Squares Path Modeling) revealed that water temperature (WT), dissolved oxygen (DO), and pH influenced the seasonal dynamic of eukaryotic microbial communities significantly, of which WT was the primary driving factor. In addition to environmental factors, water diversion is likely to be an important influencing factor. The results of the co-occurrence network and robustness suggested that the spring network is the most complex and exhibits the highest stability. Moreover, keystone taxa within networks have been identified, revealing that these key groups encompass both abundant and rare species, with specificity to different seasons. These insights are vital for understanding the seasonal variation of microbial communities in the Jihongtan Reservoir during ongoing water diversions.

Efficacy and safety of immune checkpoint inhibitors as neoadjuvant therapy in perioperative patients with non-small cell lung cancer: a network meta-analysis and systematic review based on randomized controlled trials.

Background: Randomized controlled trials (RCTs) have unequivocally established the therapeutic advantages of combining immune checkpoint inhibitors (ICIs) with chemotherapy in the treatment of early-stage non-small cell lung cancer (NSCLC). Presently, numerous perioperative immunotherapy regimens centered around the integration of ICIs and chemotherapy have undergone clinical trials. Nonetheless, due to the absence of direct comparative RCTs among these treatment regimens, this study aims to employ Bayesian network meta-analysis to ascertain the optimal combination of ICIs and chemotherapy. Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science databases, and major international conference publications up to April 10, 2024. This comprehensive search yielded a total of 1434 studies. Following a rigorous screening process that involved evaluating the studies for relevance, methodological quality, and alignment with our research objectives, 8 studies were carefully selected for inclusion in the final analysis. Based on these curated search results, a systematic review and network meta-analysis were conducted. Results: 8 RCTs were included, encompassing 7 treatments and involving 3699 operable NSCLC patients at stages I-III. Compared to chemotherapy alone, perioperative immunotherapy demonstrated higher efficacy. The combination of toripalimab and chemotherapy showed the most significant improvement in event-free survival (EFS) (HR= 0.40; 95% CI, 0.28-0.58). The regimen that most notably enhanced overall survival (OS) was Nivolumab combined with chemotherapy (HR = 0.62; 95% CI, 0.36-1.07). In terms of pathological complete response (pCR), the combination of Toripalimab and chemotherapy exhibited the highest benefit (OR = 32.89; 95% CI, 7.88-137.32). Regarding the improvement in R0 resection, Pembrolizumab plus chemotherapy performed most prominently(OR=2.15; 95% CI, 1.30-3.56). In terms of the incidence of grade 3 or higher adverse events, durvalumab combined with chemotherapy had the lowest incidence (OR = 1.05; 95% CI, 0.79-1.38), while the incidence for other regimens was higher than chemotherapy alone. Conclusion: The efficacy of perioperative immunotherapy plus chemotherapy in patients with early NSCLC is significantly improved compared to chemotherapy alone. Although there is a certain risk of adverse events, the safety is within a controllable range. After a comprehensive evaluation of five endpoints in this study, it is believed that the combination of Toripalimab or Nivolumab with chemotherapy may be the optimal immunotherapy regimen for the treatment of stage Ib-IIIb NSCLC. These findings will help guide the design of clinical treatment plans and ICIs selection. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42024536799.

Tenofovir versus entecavir on decreasing risk of HBV-related hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND: Recent studies have proved that tenofovir disoproxil fumarate (TDF) is associated with a lower risk of hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B (CHB) patients and HCC recurrence in patients who underwent hepatectomy when compared to ETV. However, it is unclear whether TDF and ETV treatment, which are both recommended as first-line antiviral agents to prevent the hepatitis B (HBV) recurrence after liver transplantation (LT), are associated with equivalent prognosis. We aim to compare risk of HCC recurrence and survival of patients recieving TDF or ETV after LT for HBV-related HCC. METHOD: We performed a retrospective study including 316 patients who received treatment with ETV or TDF after LT for HBV-related HCC from 2015 January to 2021 Augest. The Recurrence-free survival (RFS) and overall survival (OS) of TDF and ETV groups were analyzed and compared by propensity score-matched (PSM), multivariable Cox regression analysis, competing risk analysis, sensitivity analyses and subgroup analyses. RESULT: Compared with ETV, TDF therapy was associated with significantly higher RFS rates in the entire cohort (P < 0.01), PSM cohort (P < 0.01) and beyond-Milan cohort (P < 0.01). By multivariable analysis, TDF group was associated with significantly lower rates of HCC recurrence (HR, 0.33; 95%CI, 0.14-0.75; P < 0.01). In subgroup analyses, the similar results were observed in patients with following tumor characteristics: Maximum diameter plus number of viable tumor ≥ 5, with MIV or MAT, AFP at LT ≥ 20 ng/ml, and well or moderate tumor grade. CONCLUSION: Tenofovir decrease risk of HBV-Related Hepatocellular Carcinoma recurrence after liver transplantation compared to Entecavir.

An Injectable Epigenetic Autophagic Modulatory Hydrogel for Boosting Umbilical Cord Blood NK Cell Therapy Prevents Postsurgical Relapse of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) exhibits resistance to conventional treatments due to the presence of cancer stem cells (CSCs), causing postsurgical relapse and a dismal prognosis. Umbilical cord blood natural killer (UCB-NK) cell-based immunotherapy represents a promising strategy for cancer treatment. However, its therapeutic efficacy is greatly restrained by downregulation of the NK cell activation ligand MHC class I-related chain A/B (MICA/B) and autophagy-mediated degradation of NK cell-derived granzyme B (GZMB) in CSCs. Herein, it is demonstrated that suberoylanilide hydroxamic acid (SAHA) epigenetically downregulates let-7e-5p and miR-615-3p to increase MICA/B expression and that 3-methyl adenine (3MA) inhibits autophagy-mediated GZMB degradation, thereby sensitizing breast CSCs to UCB-NK cells. Then, an injectable hydrogel is designed to codeliver SAHA and 3MA to enhance UCB-NK cell infusion efficacy in TNBC. The hydrogel precursors can be smoothly injected into the tumor resection bed and form a stable gel in situ, allowing for a pH-sensitive sustained release of SAHA and 3MA. Moreover, UCB-NK cell infusion in combination with the hydrogel efficiently controls postsurgical relapse of TNBC. In addition, the hydrogel exhibits good hemostasis and wound-healing functions. Therefore, the work provides proof of concept that an injectable epigenetic autophagic modulatory hydrogel augments UCB-NK cell therapy to combat postsurgical relapse of TNBC.

Injectable adhesive hemostatic gel with tumor acidity neutralizer and neutrophil extracellular traps lyase for enhancing adoptive NK cell therapy prevents post-resection recurrence of hepatocellular carcinoma.

Post-resection recurrence remains an intractable problem in hepatocellular carcinoma (HCC) management. Natural killer (NK) cell infusion is considered as a promising cancer therapy, but acidic tumor microenvironment (TME) and neutrophil extracellular traps (NETs) greatly counteract its efficacy. Recently, polymer hydrogels have aroused much interest in tumor combination therapy, since they load and controllably release therapeutic agents with high bioavailability and low systemic toxicity. Therefore, a biocompatible hydrogel with tumor acidity neutralizer and NETs lyase may show promise for enhancing NK infusion to prevent post-resection HCC recurrence. Herein, a dual pH-responsive hydrogel with tumor acidity neutralizer (mesoporous bioactive glass nanoparticles) and NETs lyase (Deoxyribonuclease I, DNase I) is developed and used in combination with NK cell infusion for preventing post-resection HCC recurrence. The hydrogel can be injected to surgical margin and form an adhesive gel with a rapid hemostasis. Besides, it neutralizes tumor acidity to reduce tumor infiltration of immunosuppressive cells, and releases DNase I in a pH-responsive manner to degrade NETs. Moreover, this combination therapy significantly enhances NK cell infusion to combat post-surgical HCC recurrence without systemic toxicity. This study provides proof of concept that combination of NK cell adoptive therapy and hydrogel-based delivery system can successfully prevent post-resection HCC recurrence.

Graphene ballistic nano-rectifier with very high responsivity.

Although graphene has the longest mean free path of carriers of any known electronic material, very few novel devices have been reported to harness this extraordinary property. Here we demonstrate a ballistic nano-rectifier fabricated by creating an asymmetric cross-junction in single-layer graphene sandwiched between boron nitride flakes. A mobility ∼200,000 cm(2) V(-1) s(-1) is achieved at room temperature, well beyond that required for ballistic transport. This enables a voltage responsivity as high as 23,000 mV mW(-1) with a low-frequency input signal. Taking advantage of the output channels being orthogonal to the input terminals, the noise is found to be not strongly influenced by the input. Hence, the corresponding noise-equivalent power is as low as 0.64 pW Hz(-1/2). Such performance is even comparable to superconducting bolometers, which however need to operate at cryogenic temperatures. Furthermore, output oscillations are observed at low temperatures, the period of which agrees with the lateral size quantization.

Formation of c-axis oriented ZnO optical waveguides by radio-frequency magnetron sputtering.

ZnO/Mg0.16Zn0.84O (ZnO/MgZnO) films are fabricated on x-cut and z-cut LiNbO3 (LN) substrates by radio-frequency magnetron sputtering. High transparencies are confirmed by a spectrophotometer. X-ray diffraction (XRD) spectra show that all the films are c-axis oriented. The waveguiding properties, as well as the refractive indices and thickness of the films are demonstrated and determined by prism coupling. Both transverse electric (TE) and transverse magnetic (TM) modes are measured at lambda=0.633 mum and 1.539 mum, respectively. The waveguide loss is measured at lambda=0.633 mum with a fiber probe technique. The experimental results show that high optical quality ZnO films can be obtained with MgZnO buffer layers.