Role of per- and polyfluoroalkyl substances in the cardiorenal system: Unraveling crosstalk from the network of pollutants and phenotypes.

Although per- and polyfluoroalkyl substances (PFAS) have been frequently linked to cardiovascular and renal disease separately, evidence remains scarce regarding their systematic effect. Therefore, we recruited 546 newly diagnosed acute coronary syndrome (ACS) patients and detected seven myocardial enzymes and six kidney function biomarkers. Twelve PFAS were also assessed with ultra-high-performance liquid chromatography-tandem mass spectrometry. Generalized linear model and restricted cubic spline model were applied to single pollutant analysis. Quantile g-computation was used for mixture analysis. Network model was utilized to identify central and bridge nodes of pollutants and phenotypes. In the present study, perfluorohexane sulfonic acid was positively associated with uric acid (UA) (ß= 0.04, 95% confidence interval (CI): 0.01, 0.07), and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate (ß= -0.04, 95% CI: -0.07, -0.01) but positively associated with UA (ß= 0.03, 95% CI: 0.01, 0.06). In mixture analysis, each quantile increase in the PFAS mixture was significantly associated with UA (ß= 0.08, 95% CI: 0.04, 0.11). Network analysis revealed that perfluorooctanoate, UA, and myoglobin were denoted as bridge nodes, and the first principal component of lactate dehydrogenase and creatine kinase- myocardial band was identified as the node with the highest strength and expected influence. This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network, which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.

Treatment and management of duodenal gangliocytic paraganglioma: A case report.

Gangliocytic paraganglioma (GP) is a rare neuroendocrine tumor primarily found in the duodenum, most commonly in the second and third sections of the duodenum. Diagnosis of GP is based on its distinctive histopathological characteristics, which include three types of tumor cells in varying proportions: i) Epithelioid, ii) spindle-like and iii) ganglion-shaped cells. The distribution of the three tumor cell components varies from case to case and a patient may be easily misdiagnosed if one of the components is predominant. Endoscopic submucosal dissection (ESD) or surgical resection is the ideal treatment for duodenal GP (DGP); however, biotherapy, nuclide therapy, chemotherapy, targeted therapy and immunotherapy can be selected individually for patients with postoperative recurrence, metastasis or not suitable for surgery. In the present study, a male patient with DGP experienced recurrence after ESD surgery, and so received octreotide (Novartis; 30 mg/28 days) for 12 consecutive cycles. The patient had no further symptoms of gastrointestinal bleeding and no new lesions or metastases were observed after 47 months of follow-up.

Substrate-Controlled Regioselective Cascade Reactions of Deconjugated Butenolides and Cinnamaldehydes: Access to Structurally Diverse Spirobutenolides.

Two different cascade pathways to access spirobutenolides were achieved based on the substrate-controlled regioselectivity of deconjugated butenolides. A new class of functional deconjugated butenolides was designed and exhibited superior γ-regioselectivity in the vinylogous Michael/Michael cascade reactions with cinnamaldehydes. The aryl-substituted deconjugated butenolides and cinnamaldehydes underwent a Michael/Michael/aldol/dehydration cascade process induced by double α-regioselectivities. Both conjugated and deconjugated spirobutenolides could be obtained in good yields with excellent enantioselectivities.

Legacy and alternative per- and polyfluoroalkyl substances spatiotemporal distribution in China: Human exposure, environmental media, and risk assessment.

In recent decades, China's rapid development has led to significant environmental pollution from the widespread use of chemical products. Per- and polyfluoroalkyl substances (PFAS) are among the most concerning pollutants due to their persistence and bioaccumulation. This article assesses PFAS exposure levels, distribution, and health risks in Chinese blood, environment, and food. Out of 4037 papers retrieved from November 2022 to December 31, 2023, 351 articles met the criteria. Findings show perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) as the main PFAS in both Chinese populations and the environment. The highest PFOA levels in Chinese populations were in Shandong (53.868 ng/mL), while Hubei had the highest PFOS levels (43.874 ng/mL). Similarly, water samples from Sichuan (2115.204 ng/L) and Jiangsu (368.134 ng/L) had the highest PFOA and PFOS levels, respectively. Although localized areas showed high PFAS concentrations. Additionally, developed areas had higher PFAS contamination. The researches conducted in areas such as Qinghai and Hainan remain limited, underscoring the imperative for further investigation. Temporal analysis indicates declining levels of some PFAS, but emerging alternatives require more research. Limited studies on PFAS concentrations in soil, atmosphere, and food emphasize the need for comprehensive research to mitigate human exposure.

Accurately Measuring the Infrared Spectral Emissivity of Inconel 601, Inconel 625, and Inconel 718 Alloys during the Oxidation Process.

Accurate measurement of the infrared spectral emissivity of nickel-based alloys is significant for applications in aerospace. The low thermal conductivity of these alloys limits the accuracy of direct emissivity measurement, especially during the oxidation process. To improve measurement accuracy, a surface temperature correction method based on two thermocouples was proposed to eliminate the effect of thermal conductivity changes on emissivity measurement. By using this method, the infrared spectral emissivity of Inconel 601, Inconel 625, and Inconel 718 alloys was accurately measured during the oxidation process, with a temperature range of 673-873 K, a wavelength range of 3-20 µm, and a zenith angle range of 0-80°. The results show that the emissivity of the three alloys is similar in value and variation law; the emissivity of Inconel 718 is slightly less than that of Inconel 601 and Inconel 625; and the spectral emissivity of the three alloys strongly increases in the first hour, whereafter it grows gradually with the increase in oxidation time. Finally, Inconel 601 has a lower emissivity growth rate, which illustrates that it possesses stronger oxidation resistance and thermal stability. The maximum relative uncertainty of the emissivity measurement of the three alloys does not exceed 2.6%, except for the atmospheric absorption wavebands.

A Novel Active Learning Framework for Cross-Subject Human Activity Recognition from Surface Electromyography.

Wearable sensor-based human activity recognition (HAR) methods hold considerable promise for upper-level control in exoskeleton systems. However, such methods tend to overlook the critical role of data quality and still encounter challenges in cross-subject adaptation. To address this, we propose an active learning framework that integrates the relation network architecture with data sampling techniques. Initially, target data are used to fine tune two auxiliary classifiers of the pre-trained model, thereby establishing subject-specific classification boundaries. Subsequently, we assess the significance of the target data based on classifier discrepancy and partition the data into sample and template sets. Finally, the sampled data and a category clustering algorithm are employed to tune model parameters and optimize template data distribution, respectively. This approach facilitates the adaptation of the model to the target subject, enhancing both accuracy and generalizability. To evaluate the effectiveness of the proposed adaptation framework, we conducted evaluation experiments on a public dataset and a self-constructed electromyography (EMG) dataset. Experimental results demonstrate that our method outperforms the compared methods across all three statistical metrics. Furthermore, ablation experiments highlight the necessity of data screening. Our work underscores the practical feasibility of implementing user-independent HAR methods in exoskeleton control systems.

Theoretical Kinetics of Radical-Radical Reaction NH2NH + NH2 and Its Implications for Monomethylhydrazine Pyrolysis Mechanism.

Significant discrepancies were observed between the experiments and the simulations for NH2 time-histories in monomethylhydrazine pyrolysis with the robust mechanism proposed by Pascal and Catoire. The rate of formation analyses for NH2 indicated the significance of the reaction NH2NH + NH2 = H2NN + NH3, which has not been well-defined. In this study, ab initio calculations were performed for the theoretical description of the NH2NH + NH2 chemistry. Most stationary points on the potential energy surface were quantified at the CCSD(T)/CBS//M06-2X/aug-cc-pVTZ level, and the multireference methods were employed for barrier-less reaction and some transition states. The temperature- and pressure-dependent rate coefficients were determined using classical and microcanonical variational transition state theories. Four primary reaction channels were identified as competitive: 1) The H atom abstraction reaction yielding N2H2(T) + NH3, dominating at 1350-3000 K across the 0.001-100 atm pressure range. 2) The H atom abstraction reaction forming N2H2(S) + NH3, dominating at 800-1350 K and competing with the processes of chemical activation and collisional stabilization below 800 K. 3) The chemical-activated reaction resulting in H2NN(S) + NH3, dominating below 800 K at 0.001 atm. 4) The collisional-stabilized recombination reaction leading to N3H5, becoming significant as pressure increases and dominating below 600 and 650 K at 1 and 100 atm, respectively. The implications of newly calculated NH2NH + NH2 kinetics for the monomethylhydrazine pyrolysis mechanism were evaluated, and updates were implemented. Sensitivity analyses indicated the necessity of additional research efforts to comprehend the dynamics of CH3NH2 unimolecular and N2H2 + NH2 reaction systems. The rate coefficients presented in this study can be employed to develop the chemical kinetic model of nitryl-containing systems.

SAP130 mediates crosstalk between hepatocyte ferroptosis and M1 macrophage polarization in PFOS-induced hepatotoxicity.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant widely utilized in industrial manufacturing and daily life, leading to significant environmental accumulation and various public health issues. This study aims to characterize spliceosome-associated protein 130 (SAP130) as a key mediator of crosstalk between hepatocytes and macrophages, elucidating its role in PFOS-induced liver inflammation. The data demonstrate that PFOS exposure induces ferroptosis in mouse liver and AML12 cells. During ferroptosis, SAP130 is released from injured hepatocytes into the microenvironment, binding to macrophage-inducible C-type lectin (Mincle) and activating the Mincle/Syk signaling pathway in macrophages, ultimately promoting M1 polarization and exacerbating liver injury. Treatment with the ferroptosis inhibitor Ferrostatin-1 reduces SAP130 release, inhibits Mincle/Syk signaling activation, and mitigates inflammatory response. Furthermore, siSAP130 suppresses the activation of the Mincle signaling pathway and M1 polarization in BMDM cells. Conversely, treatment with the ferroptosis agonist Erastin enhances paracrine secretion of SAP130 and exacerbates inflammation. These findings emphasize the significance of hepatocyte-macrophage crosstalk as a critical pathway for PFOS-induced liver injury in mice while highlighting SAP130 as a pivotal regulator of ferroptosis and inflammation, thereby elucidating the potential mechanism of PFOS-induced liver injury.

Targeting Decidual CD16+ Immune Cells with Exosome-Based Glucocorticoid Nanoparticles for Miscarriage.

Immune dysfunction in early pregnancy including overactivation of cytotoxic CD16+ NK cells and proinflammatory M1 macrophages at the maternal-fetal interface interferes with trophoblast invasion, spiral artery remodeling, and decidualization, potentially leading to miscarriage. Immunosuppressants like glucocorticoids (GCs) are used to regulate the immune microenvironment in clinical treatment, but the lack of safe and efficient tissue-specific drug delivery systems, especially immune cell-specific vectors, limits their widespread clinical application. Here, a previously uncharacterized delivery system is reported, termed GC-Exo-CD16Ab, in which GCs are loaded into purified exosomes derived from human umbilical cord mesenchymal stem cells, and subsequently decorated with antibody CD16Ab. GC-Exo-CD16Ab is biocompatible and has remarkable delivery efficiency toward CD16+ decidual natural killer (NK) cells and CD16+ macrophages in mice. This innovative approach effectively suppresses the cytotoxicity of decidual NK cells, inhibits M1 macrophage polarization, and regulates the decidual microenvironment, thereby enhancing placental and fetal morphology, and ultimately mitigating miscarriage risk in the abortion-prone mice. The developed GC-Exo-CD16Ab provides a feasible platform for precise and tissue-specific therapeutic strategies for miscarriage and pregnancy-related diseases.

Intravitreal Injection of Conbercept Combined with Dexamethasone for Macular Edema Following Central Retinal Vein Occlusion.

Background: To compare the efficacy of intravitreal injections of Conbercept combined with dexamethasone (DEX) for macular edema (ME) following central retinal vein occlusion (CRVO). Methods: This was a prospective, single-masked, randomised, controlled clinical trial. Patients with ME following CRVO were randomised into groups to receive intravitreal injections of 0.5 mg Conbercept plus 0.2 mg DEX or 0.5 mg Conbercept alone on day 0 followed by repeat injections as indicated. The primary outcome measure was the change in best-corrected visual acuity (BCVA) from baseline to month 12. Secondary outcome measures included decrease in central retinal thickness (CRT), injection frequency and interval and percentage of patients who gained more than 15 ETDRS letters or achieved a CRT of < 250 µm at month 12. Results: 33 males (51%) and 32 females (49%) were initially recruited with an average age of 56.64 ± 13.88 years. Patients in the Conbercept and Conbercept + DEX groups gained an average of 14.55 ± 19.19 and 14.88 ± 17.68 ETDRS letters, respectively, at months 12 (t = 4.221, P = 0.000; and t = 4.834, P = 0.000) with no significant difference between the two groups (t = 0.071, P = 0.943). In the Conbercept group, the mean reduction in CRT from baseline to month 12 was 435.26 ± 293.37 µm (t = 8.261, P = 0.000) compared to 431.36 ± 294.55 (t = 8.413, P = 0.000) in the Conbercept + DEX group. There was no significant difference between the two groups (t = 0.053, P = 0.958). The Conbercept + DEX group received fewer intravitreal injections. No major complications occurred. Conclusion: Conbercept, alone or with DEX, can improve BCVA and reduce CRT in ME following CRVO without serious adverse events. The treatment interval was longer in the Conbercept + DEX group. Trial Registration: The study was registered with the Chinese Clinical Trial Registry at 5 July 2017. (http://www.chictr.org.cn, 05/07/2017 Registration Number: ChiCTR-INR-17011877).

Auraptene-ameliorating depressive-like behaviors induced by lipopolysaccharide combined with chronic unpredictable mild stress in mice mitigate hippocampal neuroinflammation mediated by microglia.

An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-ß (TGF-ß) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.

Advancements in Characterization Techniques for Microemulsions: From Molecular Insights to Macroscopic Phenomena.

Microemulsions are thermodynamically stable, optically isotropic, transparent, or semi-transparent mixed solutions composed of two immiscible solvents stabilized by amphiphilic solutes. This comprehensive review explores state-of-the-art techniques for characterizing microemulsions, which are versatile solutions essential across various industries, such as pharmaceuticals, food, and petroleum. This article delves into spectroscopic methods, nuclear magnetic resonance, small-angle scattering, dynamic light scattering, conductometry, zeta potential analysis, cryo-electron microscopy, refractive index measurement, and differential scanning calorimetry, examining each technique's strengths, limitations, and potential applications. Emphasizing the necessity of a multi-technique approach for a thorough understanding, it underscores the importance of integrating diverse analytical methods to unravel microemulsion structures from molecular to macroscopic scales. This synthesis provides a roadmap for researchers and practitioners, fostering advancements in microemulsion science and its wide-ranging industrial applications.

Discovery and biological evaluation of biaryl acetamide derivatives as selective and in vivo active sphingosine kinase-2 inhibitors.

Sphingosine kinase 2 (SphK2) has emerged as a promising target for cancer therapy due to its critical role in tumor growth. However, the lack of potent and selective inhibitors has hindered its clinical application. Herein, we report the design and synthesis of a series of novel SphK2 inhibitors, culminating in the identification of compound 12q as a highly selective and potent inhibitor of SphK2. Molecular dynamics simulations suggest that the incorporation of larger substitution groups facilitates a more effective occupation of the binding site, thereby stabilizing the complex. Compared to the widely used inhibitor ABC294640, compound 12q exhibits superior anti-proliferative activity against various cancer cells, inducing G2 phase arrest and apoptosis in liver cancer cells HepG2. Notably, 12q inhibited migration and colony formation in HepG2 and altered intracellular sphingolipid content. Moreover, intraperitoneal administration of 12q in mice resulted in decreased levels of S1P. 12q provides a valuable tool compound for exploring the therapeutic potential of targeting SphK2 in cancer.

PM2.5 exposure inhibits osteoblast differentiation by increasing the ubiquitination and degradation of Smad4.

Increasing epidemiological evidence has shown that PM2.5 exposure is significantly associated with the occurrence of osteoporosis. It has been well demonstrated that PM2.5 exposure enhanced the differentiation and function of osteoclasts by indirectly causing chronic inflammation, while the mechanism in osteoblasts remains unclear. In our study, toxic effects were evaluated by direct exposure of 20-80 µg/ml PM2.5 to MC3T3-E1 cells and BMSCs. The results showed that PM2.5 exposure did not affect cell viability via proliferation and apoptosis, but significantly inhibited osteoblast differentiation in a dose-dependent manner. Osteogenic transcription factors Runx2 and Sp7 and other biomarkers Alp and Ocn decreased after PM2.5 exposure. RNA-seq revealed TGF-ß signaling was involved in PM2.5 exposure inhibited osteoblast differentiation, which led to P-Smad1/5 and P-Smad2 reduction in the nucleus by increasing the ubiquitination and degradation of Smad4. At last, the inflammation response increased in MC3T3-E1 cells with PM2.5 exposure. Moreover, the mRNA levels of Mmp9 increased in bone marrow-derived macrophage cells treated with the conditional medium collected from MC3T3-E1 cells exposed to PM2.5. Overall, these results indicated that PM2.5 exposure inhibits osteoblast differentiation and concurrently increases the maturation of osteoclasts. Our study provides in-depth mechanistic insights into the direct impact of PM2.5 exposure on osteoblast, which would indicate the unrecognized role of PM2.5 on osteoporosis.

BIRC3-HSP90B1 Interaction Inhibits Non-Small Cell Lung Cancer Progression through the Extracellular Signal-Regulated Kinase Pathway.

The long-term prognosis of nonsmall cell lung cancer (NSCLC) remains unsatisfactory, which is a major challenge in lung cancer treatment. BIRC3 is an inhibitor of apoptosis (IAP) protein that contributes to tumor regulation. However, the underlying regulatory mechanisms of BIRC3 in NSCLC remains unknown. We initiated an analysis of BIRC3 expression data in NSCLC tumors and adjacent tissues using the TCGA and GEO databases and examined the variations in prognosis. Further, we conducted overexpression (OE) and knockdown (KD) studies on BIRC3 to evaluate its effects on NSCLC cell proliferation, migration, and invasion. Additionally, through utilization of a nude mouse model, the regulatory effects of BIRC3 on NSCLC were verified in vivo. Co-immunoprecipitation (Co-IP) assay served to pinpoint the proteins with which BIRC3 interacts. The results indicated that BIRC3 is down-regulated in NSCLC tissues and that patients with high BIRC3 expression demonstrate a better prognosis. BIRC3 is a tumor suppressor, inhibiting the proliferation and metastasis of NSCLC. Co-IP results revealed that BIRC3 interacts with HSP90B1, leading to a decrease in HSP90B1 expression and subsequent negative regulation of the ERK signaling pathway. BIRC3 may serve as a prognostic biomarker for NSCLC. It directly interacts with HSP90B1 to negatively regulate the ERK signaling pathway, thereby hindering the progression of NSCLC.

Synergy of Oxygen Vacancy and Surface Modulation Endows Hollow Hydrangea-like MnCo2O4.5 with Enhanced Capacitive Performance.

Surface chemistry and bulk structure jointly play crucial roles in achieving high-performance supercapacitors. Here, the synergistic effect of surface chemistry properties (vacancy and phosphorization) and structure-derived properties (hollow hydrangea-like structure) on energy storage is explored by the surface treatment and architecture design of the nanostructures. The theoretical calculations and experiments prove that surface chemistry modulation is capable of improving electronic conductivity and electrolyte wettability. The structural engineering of both hollow and nanosheets produces a high specific surface area and an abundant pore structure, which is favorable in exposing more active sites and shortens the ion diffusion distance. Benefiting from its admirable physicochemical properties, the surface phosphorylated MnCo2O4.5 hollow hydrangea-like structure (P-MnCoO) delivers a high capacitance of 425 F g-1 at 1 A g-1, a superior capability rate of 63.9%, capacitance retention at 10 A g-1, and extremely long cyclic stability (91.1% after 10,000 cycles). The fabricated P-MnCoO/AC asymmetric supercapacitor achieved superior energy and power density. This work opens a new avenue to further improve the electrochemical performance of metal oxides for supercapacitors.

Dinuclear Titanium(III)-Catalyzed Radical-Type Kinetic Resolution of Epoxides for the Enantioselective Synthesis of cis-Glycidic Esters.

Glycidic esters represent pivotal constituents in synthetic chemistry, offering enhanced versatility for tailoring toward a diverse array of molecular targets in comparison with simple epoxides. While considerable progress has been made in the asymmetric synthesis of trans- and trisubstituted glycidic esters, achieving enantioselective preparation of cis-glycidic esters has remained a long-standing challenge. Here, we demonstrate a selectivity-predictable modular platform for the asymmetric synthesis of cis-glycidic esters via a novel dinuclear (salen)titanium(III)-catalyzed radical-type kinetic resolution (KR) approach. This radical KR protocol operates under mild conditions and demonstrates a wide substrate scope, facilitating the synthesis of alkyl- and aryl-substituted cis-glycidic esters with high levels of regioselectivity and enantioselectivity, along with hydroxy ester byproducts representing synthetically valuable motifs as well. This study presents a unique exploration of radical-type KR applied to epoxides, effectively overcoming the steric challenges inherent in conventional nucleophilic-type methodologies typically employed in epoxide chemistry.

Biomimetic Frustrated Lewis Pair Catalysts for Hydrogenation of CO to Methanol at Low Temperatures.

The industrial production of methanol through CO hydrogenation using the Cu/ZnO/Al2O3 catalyst requires harsh conditions, and the development of new catalysts with low operating temperatures is highly desirable. In this study, organic biomimetic FLP catalysts with good tolerance to CO poison are theoretically designed. The base-free catalytic reaction contains the 1,1-addition of CO into a formic acid intermediate and the hydrogenation of the formic acid intermediate into methanol. Low-energy spans (25.6, 22.1, and 20.6 kcal/mol) are achieved, indicating that CO can be hydrogenated into methanol at low temperatures. The new extended aromatization-dearomatization effect involving multiple rings is proposed to effectively facilitate the rate-determining CO 1,1-addition step, and a new CO activation model is proposed for organic catalysts.

Fabrication-induced even-odd discrepancy of magnetotransport in few-layer MnBi2Te4.

The van der Waals antiferromagnetic topological insulator MnBi2Te4 represents a promising platform for exploring the layer-dependent magnetism and topological states of matter. Recently observed discrepancies between magnetic and transport properties have aroused controversies concerning the topological nature of MnBi2Te4 in the ground state. In this article, we demonstrate that fabrication can induce mismatched even-odd layer dependent magnetotransport in few-layer MnBi2Te4. We perform a comprehensive study of the magnetotransport properties in 6- and 7-septuple-layer MnBi2Te4, and reveal that both even- and odd-number-layer device can show zero Hall plateau phenomena in zero magnetic field. Importantly, a statistical survey of the optical contrast in more than 200 MnBi2Te4 flakes reveals that the zero Hall plateau in odd-number-layer devices arises from the reduction of the effective thickness during the fabrication, a factor that was rarely noticed in previous studies of 2D materials. Our finding not only provides an explanation to the controversies regarding the discrepancy of the even-odd layer dependent magnetotransport in MnBi2Te4, but also highlights the critical issues concerning the fabrication and characterization of 2D material devices.