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Among all the stromal cells that present in the tumor microenvironment, cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor mesenchyme, which not only provide physical support for tumor cells but also play a key role in promoting and retarding tumorigenesis in a context-dependent manner. CAFs have also been involved in the modulation of many components of the immune system, and recent studies have revealed their roles in immune evasion and poor responses to cancer immunotherapy. In this review, we describe our current understanding of the tumorigenic significance, origin, and heterogeneity of CAFs, as well as the roles of different CAFs subtypes in distinct immune cell types. More importantly, we highlight potential therapeutic strategies that target CAFs to unleash the immune system against the tumor.

With the development of wearable devices and hafnium-based ferroelectrics (FE), there is an increasing demand for high-performance flexible ferroelectric memories. However, developing ferroelectric memories that simultaneously exhibit good flexibility and significant performance has proven challenging. Here, we developed a high-performance flexible field-effect transistor (FeFET) device with a thermal budget of less than 400 °C by integrating Zr-doped HfO 2 (HZO) and ultra-thin indium tin oxide (ITO). The proposed FeFET has a large memory window (MW) of 2.78 V, a high current on/off ratio (I ON /I OFF ) of over 10 8 , and high endurance up to 2×10 7 cycles. In addition, the FeFETs under different bending conditions exhibit excellent neuromorphic properties. The device exhibits excellent bending reliability over 5×10 5 pulse cycles at a bending radius of 5 mm. The efficient integration of hafnium-based ferroelectric materials with promising ultrathin channel materials (ITO) offers unique opportunities to enable high-performance back-end-of-line (BEOL) compatible wearable FeFETs for edge intelligence applications. Using Zr-doped HfO2 and ultra-thin indium tin oxide, Li et al. develop flexible field-effect transistors with a memory window of 2.78 V and bending reliability to enable high-performance back-end-of-line compatible wearable devices.

Patients with severe carbapenem-resistant Acinetobacter baumannii (CRAB) infections currently face significant treatment challenges. When patients display signs of infection and the clinical suspicion of CRAB infections is high, appropriate treatment should be immediately provided. However, current treatment plans and clinical data for CRAB are limited. Inherent and acquired resistance mechanisms, as well as host factors, significantly restrict options for empirical medication. Moreover, inappropriate drug coverage can have detrimental effects on patients. Most existing studies have limitations, such as a restricted sample size, and are predominantly observational or non-randomized, which report significant variability in patient infection severity and comorbidities. Therefore, a gold-standard therapy remains lacking. Current and future treatment options of infections due to CRAB were described in this review. The dose and considerable side effects restrict treatment options for polymyxins, and high doses of ampicillin-sulbactam or tigecycline appear to be the best option at the time of initial treatment. Moreover, new drugs such as durlobactam and cefiderocol have substantial therapeutic capabilities and may be effective salvage treatments. Bacteriophages and antimicrobial peptides may serve as alternative treatment options in the near future. The advantages of a combination antimicrobial regimen appear to predominate those of a single regimen. Despite its significant nephrotoxicity, colistin is considered a primary treatment and is often used in combination with antimicrobials, such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin. The Infectious Diseases Society of America (IDSA) has deemed high-dose ampicillin-sulbactam, which is typically combined with high-dose tigecycline, polymyxin, and other antibacterial agents, the best option for treating serious CRAB infections. A rational combination of drug use and the exploration of new therapeutic drugs can alleviate or prevent the effects of CRAB infections, shorten hospital stays, and reduce patient mortality.

Background Besides featured glucose consumption, recent studies reveal that cancer cells might prefer “addicting” specific energy substrates from the tumor microenvironment (TME); however, the underlying mechanisms remain unclear. Methods Fibroblast-specific long noncoding RNAs were screened using RNA-seq data of our NJLCC cohort, TCGA, and CCLE datasets. The expression and package of LINC01614 into exosomes were identified using flow cytometric sorting, fluorescence in situ hybridization (FISH), and quantitative reverse transcription polymerase chain reaction (RT-PCR). The transfer and functional role of LINC01614 in lung adenocarcinoma (LUAD) and CAFs were investigated using 4-thiouracil-labeled RNA transfer and gain- and loss-of-function approaches. RNA pull-down, RNA immunoprecipitation, dual-luciferase assay, gene expression microarray, and bioinformatics analysis were performed to investigate the underlying mechanisms involved. Results We demonstrate that cancer-associated fibroblasts (CAFs) in LUAD primarily enhance the glutamine metabolism of cancer cells. A CAF-specific long noncoding RNA, LINC01614, packaged by CAF-derived exosomes, mediates the enhancement of glutamine uptake in LUAD cells. Mechanistically, LINC01614 directly interacts with ANXA2 and p65 to facilitate the activation of NF-κB, which leads to the upregulation of the glutamine transporters SLC38A2 and SLC7A5 and eventually enhances the glutamine influx of cancer cells. Reciprocally, tumor-derived proinflammatory cytokines upregulate LINC01614 in CAFs, constituting a feedforward loop between CAFs and cancer cells. Blocking exosome-transmitted LINC01614 inhibits glutamine addiction and LUAD growth in vivo. Clinically, LINC01614 expression in CAFs is associated with the glutamine influx and poor prognosis of patients with LUAD. Conclusion Our study highlights the therapeutic potential of targeting a CAF-specific lncRNA to inhibit glutamine utilization and cancer progression in LUAD.

The visual system must make predictions to compensate for inherent delays in its processing. Yet little is known, mechanistically, about how prediction aids natural behaviors. Here, we show that despite a 20-30ms intrinsic processing delay, the vertical motion sensitive (VS) network of the blowfly achieves maximally efficient prediction. This prediction enables the fly to fine-tune its complex, yet brief, evasive flight maneuvers according to its initial ego-rotation at the time of detection of the visual threat. Combining a rich database of behavioral recordings with detailed compartmental modeling of the VS network, we further show that the VS network has axonal gap junctions that are critical for optimal prediction. During evasive maneuvers, a VS subpopulation that directly innervates the neck motor center can convey predictive information about the fly’s future ego-rotation, potentially crucial for ongoing flight control. These results suggest a novel sensory-motor pathway that links sensory prediction to behavior.

This review compares the efficacy of Uterine Artery Embolization (UAE) and Myomectomy (MYO) in managing symptomatic Uterine Fibroids (UFs) in women who do not want hysterectomy. A meta-analysis was performed on all available studies that evaluated the relative benefits and harms of MYO and UEA for the management of patients suffering from UFs. Outcomes evaluated reintervention, UFs scores for quality of life (QOL) and symptom severity, and other complications. To determine mean differences (MDs) or odds ratios (ORs) with 95% confidence intervals (CIs), a random or fixed-effects model was utilized. A meta-analysis of 13 studies (9 observational and 4 randomized controlled trials) was conducted. The results indicated that UAE had a higher reintervention rate (OR 1.84; 95% CI 1.62–2.10; P  < 0.01; I 2  = 39%), hysterectomy rate (OR 4.04; 95% CI 3.45–4.72; P  < 0.01; I 2  = 59%), and symptom-severity score (OR − 4.02; 95% CI 0.82, 7.22; P  = 0.01; I 2  = 0%) compared to MYO at a four-year follow-up. However, UAE was associated with a lower rate of early complications (OR 0.44; 95% CI 0.20–0.95; P  = 0.04; I 2  = 25%), and readmission rate (OR 1.16; 95% CI 1.01–1.33; P  = 0.04; I 2  = 0%) compared to MYO. Furthermore, both procedures had comparable improvement in pregnancy rates and abnormal uterine bleeding. In conclusion, UAE and MYO are effective in treating symptomatic UFs but they have different outcomes. The decision on which procedure to choose should be made based on individual preferences and the physician’s expertise.

This report presents the development of a highly effective method employing high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) to investigate chlorantraniliprole’s dissipation, risk assessment, and residue distribution in whole lychee fruit and its pulp. Mean recoveries of the samples ranged from 80 to 105%, exhibiting a relative standard deviation (RSD) of below 8%. The limits of quantification (LOQ) for lychee and pulp were determined as 0.001 mg/kg, and half-lives (t1/2) ranged from 8.0 to 12.2 days. Terminal residue concentrations in whole litchi and pulp were determined as 0.008–0.45 mg/kg and ≤0.001 mg/kg. These residues were treated twice and thrice at two different dosage levels with pre-harvest intervals (PHIs) of 7, 14, and 21 days. The potential chronic risk posed by chlorantraniliprole to humans was non-negligible, as indicated by the risk quotient (RQ) value not exceeding 1. Therefore, this study provides significant fresh data about the safe application of chlorantraniliprole in the production of lychee, which will help China develop maximum residual limits (MRLs).

In non-Hermitian systems, the dynamic encircling of exceptional points (EPs) engenders intriguing chiral phenomena, where the resultant state characteristics are intrinsically dependent upon the encircling handedness. An ingenious approach using simple leaky optical elements has been presented to emulate this chiral behavior without physically encircling an EP. This innovative simplification of EP properties enables a more straightforward implementation of asymmetric switching of polarization and path. Given that photons inherently possess multiple physical degrees of freedom, the research focus has shifted from single-dimensional to multidimensional asymmetric switching. Hence, there is a fundamental challenge of how to achieve multidimensional asymmetric switching through a simple and universally applicable architecture. Here, we propose and experimentally demonstrate a novel topology-optimized architecture, termed EP-encirclement emulation tailoring, enabling multidimensional asymmetric switching. Theoretical analysis reveals that our architecture eliminates the 3-dB inherent loss in conventional architecture by replacing couplers with (de)multiplexers. Building upon this architecture, we harness all-fiber devices to implement a high-performance asymmetric switching of polarization, mode, and orbital angular momentum (OAM). To our knowledge, this is the first experimental demonstration of asymmetric OAM switching to date. Our work provides an efficient topology architecture for emulating dynamic EP encirclement, paving the way for universal and flexible asymmetric switching devices.

The present study describes the development of a highly effective approach for determining the residue distribution and dissipation of trifloxystrobin and tebuconazole, and their risk assessment in brown rice, husk, straw, and grain using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). The current study provides considerable novel information regarding the safe utilization of a mixture of trifloxystrobin and tebuconazole in paddy production. The samples demonstrated a range of mean recoveries between 72% and 86%, with a 1.1–9.2% relative standard deviation (RSD). The limits of quantification (LOQ) and half-lives (t1/2) for brown rice, husk, straw, and grain were, respectively, established to be 0.001–0.01 mg/kg and 4.1–7.7 days. The concentrations of terminal residues in the brown rice, husk, straw, and grain were, respectively, found to be 0.02–0.05, 0.03–0.11, 0.02–0.07, and 0.02–0.05 mg/kg after being treated twice at 168.75 g a.i./ha with 21 and 28 days of pre-harvest intervals (PHIs). Trifloxystrobin and tebuconazole presented a non-negligible chronic risk to human subjects, as evidenced by a risk quotient (RQ) value of less than 1.

A derivatization method combined with high-performance liquid chromatography–fluorescence detection (HPLC–FLD) was used to evaluate the dissipation, residue distribution and risk assessment of emamectin benzoate in whole longan and pulp. The average recoveries were 82–111% with relative standard deviation (RSD) less than 11%. The limit of quantification (LOQ) was 0.001 mg/kg in longan and pulp. The half-lives were 3.3–4.2 days. The terminal residues in whole longan were <0.001–0.025 mg/kg applied two and three times at two levels of dosage with PHIs of 10, 14, and 21 days. The residues in whole longan had a higher quantity than those in the pulp, and the terminal residues of pulp were all lower than LOQ (0.001 mg/kg). The chronic risk of emamectin benzoate was not negligible to humans depending on ADI% value, which was higher than 1; and the acute risk was acceptable to the consumer. This study could provide guidance for the safe use of emamectin benzoate in longan and serve as a reference for the establishment of maximum residue limits (MRLs) in China.