Nano- and microplastics drive the dynamic equilibrium of amoeba-associated bacteria and antibiotic resistance genes.

As emerging pollutants, microplastics have become pervasive on a global scale, inflicting significant harm upon ecosystems. However, the impact of these microplastics on the symbiotic relationship between protists and bacteria remains poorly understood. In this study, we investigated the mechanisms through which nano- and microplastics of varying sizes and concentrations influence the amoeba-bacterial symbiotic system. The findings reveal that nano- and microplastics exert deleterious effects on the adaptability of the amoeba host, with the magnitude of these effects contingent upon particle size and concentration. Furthermore, nano- and microplastics disrupt the initial equilibrium in the symbiotic relationship between amoeba and bacteria, with nano-plastics demonstrating a reduced ability to colonize symbiotic bacteria within the amoeba host when compared to their microplastic counterparts. Moreover, nano- and microplastics enhance the relative abundance of antibiotic resistance genes and heavy metal resistance genes in the bacteria residing within the amoeba host, which undoubtedly increases the potential transmission risk of both human pathogens and resistance genes within the environment. In sum, the results presented herein provide a novel perspective and theoretical foundation for the study of interactions between microplastics and microbial symbiotic systems, along with the establishment of risk assessment systems for ecological environments and human health.

The cost-effectiveness of zolbetuximab in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma.

Aim: To estimate the cost-effectiveness of zolbetuximab plus capecitabine/oxaliplatin (CAPOX) in CLDN18.2-positive, HER2-negative, mG/GEJ adenocarcinoma from the perspective of Chinese payers. Materials & methods: A partitioned survival model was developed to assess the costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER) of zolbetuximab plus CAPOX versus placebo plus CAPOX. Sensitivity analyses were performed to test the robustness of model. Results: Zolbetuximab plus CAPOX gained an additional cost of $91,551 and an extra health benefit of 0.24 QALY over placebo plus CAPOX, producing an ICER of $388,186/QALY, which exceeded the willingness-to-pay threshold of $38,223/QALY. Sensitivity analysis shows that the model was generally robust. Conclusion: Zolbetuximab plus CAPOX would not be a cost-effective first-line treatment regimen in CLDN18.2-positive, HER2-negative, mG/GEJ adenocarcinoma in China.

[Box: see text].

Case report: Pulse cyclophosphamide for treatment of multi-agent-refractory hepatic graft-versus-host disease.

Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality in HSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies. We present the case of a 46-year-old woman diagnosed with acute undifferentiated leukemia, who exhibited persistently elevated levels of serum total bilirubin (T.Bili), alkaline phosphatase (ALP), and liver function tests (LFTs) beginning on [day +201] post-haploidentical peripheral blood stem cell (PBSC) transplantation. The patient received fludarabine/total body irradiation (Flu/TBI) as a myeloablative conditioning regimen and post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) as GVHD prophylaxis. A liver biopsy confirmed the diagnosis of GVHD, while other possible etiologies were excluded by corresponding tests. Initial treatment with prednisone and tacrolimus, and the later addition of ruxolitinib, all showed poor response indicated by worsening T.Bili, ALP, and LFTs at the same time. Based on a multidisciplinary comprehensive assessment, we decided to administer 1,000 mg/m2 (1,600 mg) of cyclophosphamide ("pulse Cy"), which resulted in a dramatic improvement in T.Bili and transaminases starting from the very next day. A durable response to pulse cyclophosphamide was observed, as all indicators normalized ("complete response") within 55 days without relapses. The patient remains in good health with no recurrence of hepatic GVHD. To our knowledge, this is the first case in which Grade IV hepatic GVHD, refractory to multiple agents including steroids, tacrolimus, and ruxolitinib, demonstrated a complete response to pulse cyclophosphamide. The success highlights the potential therapeutic role of cyclophosphamide, a potent and cost-effective chemotherapy agent, in treating multi-agent-refractory GVHD. Large-scale clinical trials are warranted to validate its efficacy in this setting.

How Fe-bearing materials affect soil arsenic bioavailability to rice: A meta-analysis.

Arsenic (As) contamination is widespread in soil and poses a threat to agricultural products and human health due to its high susceptibility to absorption by rice. Fe-bearing materials (Fe-Mat) display significant potential for reducing As bioavailability in soil and bioaccumulation in rice. However, the remediation effect of various Fe-Mat is often inconsistent, and the response to diverse environmental factors is ambiguous. Here, we conducted a meta-analysis to quantitatively assess the effects of As in soils, rice roots, and grains based on 673, 321, and 305 individual observations from 67 peer-reviewed articles, respectively. On average, Fe-Mat reduced As bioavailability in soils, rice roots, and grains by 28.74 %, 33.48 %, and 44.61 %, respectively. According to the analysis of influencing factors, the remediation efficiency of Fe-Mat on As-contaminated soil was significantly enhanced with increasing Fe content in the material, in which the industry byproduct was the most effective in soils (-42.31 %) and rice roots (-44.57 %), while Fe-biochar was superior in rice grains (-54.62 %). The efficiency of Fe-Mat in minimizing soil As mobility was negatively correlated with soil Fe content, CEC, and pH. In addition, applying Fe-Mat in alkaline soils with higher silt, lower clay and available P was more effective in reducing As in rice grains. A higher efficiency of applying Fe-Mat under continuous flooding conditions (27.39 %) compared with alternate wetting and drying conditions (23.66 %) was also identified. Our results offer an important reference for the development of remediation strategies and methods for various As-contaminated paddy soils.

Terahertz Vibrational Fingerprints Detection of Molecules with Particularly Designed Graphene Biosensors.

In this research, an arc I-shaped graphene sensing structure with multi-resonance characteristics is proposed for the simultaneous detection of vibrational fingerprints with spectral separation in the terahertz range. The resonant frequencies of the sensor can be dynamically tuned by changing the gate voltage applied to the graphene arrays. The two vibrational fingerprints of lactose molecules (0.53 THz and 1.37 THz) in the transmission spectrum can be enhanced simultaneously by strictly optimizing the geometrical parameters of the sensor. More importantly, these two resonant frequencies can be tuned precisely to coincide with the two standard resonances of the lactose molecule. The physical mechanism of the sensor is revealed by inspection of the electric field intensity distribution, and the advantage of the sensor, which is its ability to operate at a wide range of incident angles, has been demonstrated. The sensing performance of the structure as a refractive index sensor has also been studied. Finally, a double arc I-shaped graphene sensor is further designed to overcome the polarization sensitivity, which demonstrates excellent molecular detection performance under different polarization conditions. This study may serve as a reference for designing graphene biosensors for molecular detection.

Refractive index sensor with alternative high performance using black phosphorus in the all-dielectric configuration.

We theoretically propose a nonplasmonic optical refractive index sensor based on black phosphorus (BP) and other dielectric materials in the infrared band. Due to the anisotropic property of BP, the proposed sensor can achieve alternative sensitivity and figure of merit (FOM) in its different crystal directions. The high sensitivity and FOM are attributed to the strong magnetic resonance in the all-dielectric configuration. The coupled-mode theory (CMT) is used to verify the simulation results and reveal the physical mechanism. Furthermore, influences of the sample and the incident angle on the performance of the sensor are also discussed. Our design utilizes a simple dielectric structure with a BP monolayer, which exhibits great potential for the future high-performance sensor with low cost.

NEI-01-Induced Arginine Deprivation Has Potent Activity Against Acute Myeloid Leukemia Cells Both In Vitro and In Vivo.

Recent studies have revealed that targeting amino acid metabolic enzymes is a promising strategy in cancer therapy. Acute myeloid leukemia (AML) downregulates the expression of argininosuccinate synthase (ASS1), a recognized rate-limiting enzyme for arginine synthesis, and yet displays a critical dependence on extracellular arginine for survival and proliferation. This dependence on extracellular arginine, also known as arginine auxotrophy, suggests that arginine deprivation would be a treatment strategy for AML. NEI-01, a novel arginine-depleting enzyme, is capable of binding to serum albumin to extend its circulating half-life, leading to a potent anticancer activity. Here we reported the preclinical activity of NEI-01 in arginine auxotrophic AMLs. NEI-01 efficiently depleted arginine both in vitro and in vivo NEI-01-induced arginine deprivation was cytotoxic to arginine auxotrophic AML cells through induction of cell-cycle arrest and apoptosis. Furthermore, the potent anti-leukemia activities of NEI-01 were observed in three different types of mouse models including human cell line-derived xenograft, mouse cell line-derived homografts in syngeneic mice and patient-derived xenograft. This preclinical data provide strong evidence to support the potential use of NEI-01 as a therapeutic approach in AML treatment.

Proteomic screening of potential N-glycoprotein biomarkers for colorectal cancer by TMT labeling combined with LC-MS/MS.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is part of the most widespread malignant tumors. At present, colonoscopy is a routine procedure in the diagnosis of CRC, but it is traumatic. Carcinoembryonic antigen, CA199, and CA242 are common serum markers for the diagnosis of CRC; however, they do not demonstrate satisfactory specificity and sensitivity for the diagnosis of CRC. Hence, Now it is necessary to screen many valuable serum biomarkers for CRC, proteomics methods have been used to investigate PTMs such as glycosylation of proteins with prominent roles in the occurrence and development of tumors. METHODS: This study screens altering glycosylated proteins of CRC tissues using LC-MS/MS quantitative glycoproteomics, and then these candidate biomarkers for CRC are further validated by serum glycoproteomics. RESULTS: The results of glycoproteomics in CRC tissues show that the abundance of 160 and 79 glycerogelatin proteins was obviously upregulated and downregulated compared with their adjacent tissues(P < 0.05). Bioinformatics analysis suggests that these molecules are mainly involved in many biological processes, including skeletal system development, collagen fibril organization, and receptor-mediated endocytosis. Results of serum glycoproteomics show that the changing trends of 2 protein glycosylation were consistent with MS results of CRC tissues, including ICAM1and APMAP. Areas under the ROC curve (AUC) results confirm that ICAM1and APMAP as early immune diagnosis markers of CRC has excellent sensitivity and specificity. CONCLUSION: The ICAM1 and APMAP may serve as a potential tumor marker for CRC.

Efficient HIE-FDTD method for designing a dual-band anisotropic terahertz absorption structure.

The finite-difference time-domain (FDTD) method is considered to be one of the most accurate and common methods for the simulation of optical devices. However, the conventional FDTD method is subject to the Courant-Friedrich-Levy condition, resulting in extremely low efficiency for calculating two-dimensional materials (2DMs). Recent researches on the hybrid implicit-explicit FDTD (HIE-FDTD) method show that the method can efficiently simulate homogeneous and isotropic 2DMs such as graphene sheet; however, it is inapplicable to the anisotropic medium. In this paper, we propose an in-plane anisotropic HIE-FDTD method to simulate optical devices containing graphene and black phosphorus (BP) sheets. Numerical analysis shows that the proposed method is accurate and efficient. With this method, we present a novel multi-layer graphene-BP-based dual-band anisotropic terahertz absorption structure (GBP-DATAS) and analyze its optical characteristics. Combining the advantages of graphene and BP localized surface plasmons, the GBP-DATAS demonstrates strong anisotropic plasmonic resonance and high absorption rate in the terahertz band.

Single-cell RNA sequencing reveals regulation of fetal ovary development in the monkey (Macaca fascicularis).

Germ cells are vital for reproduction and heredity. However, the mechanisms underlying female germ cell development in primates, especially in late embryonic stages, remain elusive. Here, we performed single-cell RNA sequencing of 12,471 cells from whole fetal ovaries, and explored the communications between germ cells and niche cells. We depicted the two waves of oogenesis at single-cell resolution and demonstrated that progenitor theca cells exhibit similar characteristics to Leydig cells in fetal monkey ovaries. Notably, we found that ZGLP1 displays differentially expressed patterns between mouse and monkey, which is not overlapped with NANOG in monkey germ cells, suggesting its role in meiosis entry but not in activating oogenic program in primates. Furthermore, the majority of germ cell clusters that sharply express PRDM9 and SPO11 might undergo apoptosis after cyst breakdown, leading to germ cell attrition. Overall, our work provides new insights into the molecular and cellular basis of primate fetal ovary development at single-cell resolution.

Enhanced terahertz modulation using a plasmonic perfect absorber based on black phosphorus.

In this paper, we design a plasmonic perfect absorber based on black phosphorus (BP) with enhanced terahertz modulation. By tuning the chemical potential (µc) of BP, the modulation depth can reach up to 95%. The influence of geometric size and bandgap of BP on reflection spectra is also investigated. Moreover, the effect of the incident angle on the reflectance is discussed with different values of µc. Our results show that the plasmonic nanoslit mode contributes to the enhancement of the modulation effect. This simple periodical structure provides a potential route to design a tunable plasmonic BP-based modulator in the THz range.

Tunable dual-band terahertz absorber with all-dielectric configuration based on graphene.

In this paper, we theoretically design a dual-band graphene-based terahertz (THz) absorber combining the magnetic resonance with a THz cold mirror without any metallic loss. The absorption spectrum of the all-dielectric THz absorber can be actively manipulated after fabrication due to the tunable conductivity of graphene. After delicate optimization, two ultra-narrow absorption peaks are achieved with respective full width at half maximum (FWHM) of 0.0272 THz and 0.0424 THz. Also, we investigate the effect of geometric parameters on the absorption performance. Coupled mode theory (CMT) is conducted on the dual-band spectrum as an analytic method to confirm the validity of numerical results. Furthermore, physical mechanism is deeply revealed with magnetic and electric field distributions, which demonstrate a totally different principle with traditional plasmonic absorber. Our research provides a significant design guide for developing tunable multi-resonant THz devices based on all-dielectric configuration.

Generation of a human induced pluripotent stem cell line (SHUPLi001-A) from PBMCs of a healthy male donor.

Human induced pluripotent stem cells (iPSCs) are an ideal model for pathomechanism investigation and drug screening due to their differentiation potency. Here, we generated an iPSC line, SHUPLi001-A, from peripheral blood mononuclear cells (PBMCs) of a healthy 30-year-old male individual using non-integrating Sendai virus. Characterization of SHUPLi001-A was confirmed by the expression of typical pluripotency markers and by the teratoma formation assay to assess differentiation potency in vivo.

A modified arginine-depleting enzyme NEI-01 inhibits growth of pancreatic cancer cells.

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.

Efficient and risk-reduced genome editing using double nicks enhanced by bacterial recombination factors in multiple species.

Site-specific DNA double-strand breaks have been used to generate knock-in through the homology-dependent or -independent pathway. However, low efficiency and accompanying negative impacts such as undesirable indels or tumorigenic potential remain problematic. In this study, we present an enhanced reduced-risk genome editing strategy we named as NEO, which used either site-specific trans or cis double-nicking facilitated by four bacterial recombination factors (RecOFAR). In comparison to currently available approaches, NEO achieved higher knock-in (KI) germline transmission frequency (improving from zero to up to 10% efficiency with an average of 5-fold improvement for 8 loci) and 'cleaner' knock-in of long DNA fragments (up to 5.5 kb) into a variety of genome regions in zebrafish, mice and rats. Furthermore, NEO yielded up to 50% knock-in in monkey embryos and 20% relative integration efficiency in non-dividing primary human peripheral blood lymphocytes (hPBLCs). Remarkably, both on-target and off-target indels were effectively suppressed by NEO. NEO may also be used to introduce low-risk unrestricted point mutations effectively and precisely. Therefore, by balancing efficiency with safety and quality, the NEO method reported here shows substantial potential and improves the in vivo gene-editing strategies that have recently been developed.

Heterogeneous nuclear ribonucleoprotein A3 controls mitotic progression of neural progenitors via interaction with cohesin.

Cortex development is controlled by temporal patterning of neural progenitor (NP) competence with sequential generation of deep and superficial layer neurons, but underlying mechanisms remain elusive. Here, we report a role for heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) in regulating the division of early cortical NPs that mainly give rise to deep-layer neurons via direct neurogenesis. HNRNPA3 is expressed at high levels in NPs of mouse and human cortex at early stages, with a unique peri-chromosome pattern. Intriguingly, downregulation of HNRNPA3 caused chromosome disarrangement, which hindered normal separation of chromosomes during NP division, leading to mitotic delay. Furthermore, HNRNPA3 is associated with the cohesin-core subunit SMC1A and controls its association with chromosomes, implicating a mechanism for the role of HNRNPA3 in regulating chromosome segregation in dividing NPs. Hnrnpa3-deficient mice exhibited reduced cortical thickness, especially of deep layers. Moreover, downregulation of HNRNPA3 in cultured human cerebral organoids led to marked reduction in NPs and deep-layer neurons. Thus, this study has identified a crucial role for HNRNPA3 in NP division and highlighted the relationship between mitosis progression and early neurogenesis.

Tunable and Anisotropic Dual-Band Metamaterial Absorber Using Elliptical Graphene-Black Phosphorus Pairs.

We numerically propose a dual-band absorber in the infrared region based on periodic elliptical graphene-black phosphorus (BP) pairs. The proposed absorber exhibits near-unity anisotropic absorption for both resonances due to the combination of graphene and BP. Each of the resonances is independently tunable via adjusting the geometric parameters. Besides, doping levels of graphene and BP can also tune resonant properties effectively. By analyzing the electric field distributions, surface plasmon resonances are observed in the graphene-BP ellipses, contributing to the strong and anisotropic plasmonic response. Moreover, the robustness for incident angles and polarization sensitivity are also illustrated.

Graphene-Based Biosensors for Detection of Composite Vibrational Fingerprints in the Mid-Infrared Region.

In this study, a label-free multi-resonant graphene-based biosensor with periodic graphene nanoribbons is proposed for detection of composite vibrational fingerprints in the mid-infrared range. The multiple vibrational signals of biomolecules are simultaneously enhanced and detected by different resonances in the transmission spectrum. Each of the transmission dips can be independently tuned by altering the gating voltage applied on the corresponding graphene nanoribbon. Geometric parameters are investigated and optimized to obtain excellent sensing performance. Limit of detection is also evaluated in an approximation way. Besides, the biosensor can operate in a wide range of incident angles. Electric field intensity distributions are depicted to reveal the physical insight. Moreover, another biosensor based on periodic graphene nanodisks is further proposed, whose performance is insensitive to the polarization of incidence. Our research may have a potential for designing graphene-based biosensor used in many promising bioanalytical and pharmaceutical applications.