Immune checkpoint blockade resistance in lung cancer: emerging mechanisms and therapeutic opportunities.

Immune checkpoint blockade (ICB) therapy works by inhibiting suppressive checkpoints that become upregulated after T cell activation, like PD-1/PD-L1 and CTLA-4. While the initial FDA approvals of ICB have revolutionized cancer therapies and fueled a burgeoning immuno-oncology field, more recent clinical development of new agents has been slow. Here, focusing on lung cancer, we review the latest research uncovering tumor cell intrinsic and extrinsic ICB resistance mechanisms as major hurdles to treatment efficacy and clinical progress. These include genomic and non-genomic tumor cell alterations, along with host and microenvironmental factors like the microbiome, metabolite accumulation, and hypoxia. Together, these factors can cooperate to promote immunosuppression and ICB resistance. Opportunities to prevent resistance are constantly evolving in this rapidly expanding field, with the goal of moving toward personalized immunotherapeutic regimens.

Bioinspired integrated triboelectric electronic tongue.

An electronic tongue (E-tongue) comprises a series of sensors that simulate human perception of taste and embedded artificial intelligence (AI) for data analysis and recognition. Traditional E-tongues based on electrochemical methods suffer from a bulky size and require larger sample volumes and extra power sources, limiting their applications in in vivo medical diagnosis and analytical chemistry. Inspired by the mechanics of the human tongue, triboelectric components have been incorporated into E-tongue platforms to overcome these limitations. In this study, an integrated multichannel triboelectric bioinspired E-tongue (TBIET) device was developed on a single glass slide chip to improve the device's taste classification accuracy by utilizing numerous sensory signals. The detection capability of the TBIET was further validated using various test samples, including representative human body, environmental, and beverage samples. The TBIET achieved a remarkably high classification accuracy. For instance, chemical solutions showed 100% identification accuracy, environmental samples reached 98.3% accuracy, and four typical teas demonstrated 97.0% accuracy. Additionally, the classification accuracy of NaCl solutions with five different concentrations reached 96.9%. The innovative TBIET exhibits a remarkable capacity to detect and analyze droplets with ultrahigh sensitivity to their electrical properties. Moreover, it offers a high degree of reliability in accurately detecting and analyzing various liquid samples within a short timeframe. The development of a self-powered portable triboelectric E-tongue prototype is a notable advancement in the field and is one that can greatly enhance the feasibility of rapid on-site detection of liquid samples in various settings.

Luminescence of Sm3+ in double perovskite-type Ba2SrWO6 for insect trapping.

The predominant method for pest control has been the use of pesticides, which have been shown to have detrimental effects on soil, freshwater, and crop quality. Therefore, the development of novel and sustainable crop protection strategies has become increasingly imperative. In this study, a novel orange-red emitting Ba2SrWO6: Sm3+ phosphor was synthesized using the high-temperature solid-state reaction. Under ultraviolet excitation, the phosphors showed obvious emission peaks at 575, 614, and 662 nm. The Ba2SrWO6: Sm3+ was used to fabricate a fluorescence film with polydimethylsiloxane (PDMS), and attracted twice as many insects as the blank control group under 365 nm ultraviolet light. This material holds great potential as a fluorescent agent for insect trapping in the pest control fields of tea, cotton, eggplant, rice, potato, grape, and other agricultural industries. Our findings provide an eco-friendly approach to pest management for the increment of food production.

Smart windows based on ultraviolet-B persistent luminescence phosphors for bacterial inhibition and food preservation.

Herein, ultraviolet B (UVB) persistent luminescence phosphors containing SrAl12O19: Ce3+, Sc3+ nanoparticles were reported. Thermoluminescence (TL) spectrum analysis reveals that the shallow trap induced by Sc3+ co-doping plays an important role in photoluminescence persistent luminescence (PersL) development, while the deep trap dominates the generation of optical stimulated luminescence (OSL). Owing the appearance of deep trap, the OSL is observed under light (700 nm - 900 nm) excitation. UVB luminescence exerts good bactericidal effects on pathogenic bacteria involved in the process of food spoilage. Thus, the smart window with SrAl12O19: Ce3+, Sc3+/PDMS produces UVB PersL to efficiently inactivate Escherichia coli and Staphylococcus aureus. In addition, the presence of the smart window delays the critical point of pork decay, and greatly reduces the time of pork spoilage. It maximizes the convenience of eradicating bacteria and preserving food, thus offering a fresh perspective on the use of UV light for food sterilization and preservation.

A review of gluten detoxification in wheat for food applications: approaches, mechanisms, and implications.

With the improved knowledge of gluten-related disorders, especially celiac disease (CD), the market of gluten-free food is growing. However, the current gluten-free diet still presents challenges in terms of nutrition, acceptability, and cost due to the absence of gluten. It is important to note that gluten-related allergies or sensitivities have different underlying causes. And individuals with mild non-celiac gluten disorder symptoms may not necessarily require the same gluten-free treatments. Scientists are actively seeking alternative solutions for these consumers. This review delves into the various strategies employed by researchers for detoxifying gluten or modifying its main protein, gliadin, including genetic treatment, transamidation and deamidation, hydrolysis, and microbial treatments. The mechanisms, constraints of these techniques, their current utilization in food items, as well as their implications for gluten-related disorders, are discussed in detail. Although there is still a gap in the application of these methods as alternative solutions in the real market, the summary provided by our review could be beneficial for peers in enriching their basic ideas and developing more applicable solutions for wheat gluten detoxification.

Boosting broadband short-wave infrared emission to achieve near-unity quantum efficiency via bridging Cr3+-Ni2+ in spinel solid-solutions towards light-emitting diode applications.

Recently, short-wave infrared (SWIR) phosphor-converted light-emitting diodes (pc-LEDs) have garnered increased attention due to their widespread applications in night vision, biological imaging, and non-destructive testing. Nevertheless, the currently used SWIR phosphors suffer from poor thermal stability and low quantum efficiency. In this study, a finely tuned spinel-based solid solution, Mg0.5Zn0.5Ga2O4, is prepared to host Ni2+ to induce SWIR emission. Cr3+ is codoped as a sensitizer to bridge Cr3+ and Ni2+ ions, significantly enhancing blue light absorption and facilitating energy transfer (ET) to Ni2+ ions. The champion SWIR phosphor exhibits a broadband emission centered at 1304 nm with a full width at half maximum (FWHM) of 250 nm, achieving a near-unity internal quantum efficiency (IQE = 97.7%) and a good thermal stability (70.7%@423 K). The fabricated SWIR pc-LED device delivers a high SWIR output power of 39.9 mW at 360 mA, enabling its application in non-destructive imaging and testing.

Assessment of Heart Rate Monitoring During Exercise With Smart Wristbands and a Heart Rhythm Patch: Validation and Comparison Study.

BACKGROUND: The integration of wearable devices into fitness routines, particularly in military settings, necessitates a rigorous assessment of their accuracy. This study evaluates the precision of heart rate measurements by locally manufactured wristbands, increasingly used in military academies, to inform future device selection for military training activities. OBJECTIVE: This research aims to assess the reliability of heart rate monitoring in chest straps versus wearable wristbands. METHODS: Data on heart rate and acceleration were collected using the Q-Band Q-69 smart wristband (Mobile Action Technology Inc) and compared against the Zephyr Bioharness standard measuring device. The Lin concordance correlation coefficient, Pearson product moment correlation coefficient, and intraclass correlation coefficient were used for reliability analysis. RESULTS: Participants from a Northern Taiwanese medical school were enrolled (January 1-June 31, 2021). The Q-Band Q-69 demonstrated that the mean absolute percentage error (MAPE) of women was observed to be 13.35 (SD 13.47). Comparatively, men exhibited a lower MAPE of 8.54 (SD 10.49). The walking state MAPE was 7.79 for women and 10.65 for men. The wristband's accuracy generally remained below 10% MAPE in other activities. Pearson product moment correlation coefficient analysis indicated gender-based performance differences, with overall coefficients of 0.625 for women and 0.808 for men, varying across walking, running, and cooldown phases. CONCLUSIONS: This study highlights significant gender and activity-dependent variations in the accuracy of the MobileAction Q-Band Q-69 smart wristband. Reduced accuracy was notably observed during running. Occasional extreme errors point to the necessity of caution in relying on such devices for exercise monitoring. The findings emphasize the limitations and potential inaccuracies of wearable technology, especially in high-intensity physical activities.

Detoxification of Wheat Gluten by Enzymatic Transamidation under Reducing Condition and Its Application in Typical Food Model.

SCOPE: Gluten, the primary network builder of wheat dough, is responsible for celiac disease or wheat allergy. Transamidation of gluten under reduction conditions has been shown to reduce the potential toxicity of celiac disease, but its application in food preparation has not been extensively studied. This work investigates the use of transamidation in food preparation to address this gap in knowledge. METHODS AND RESULTS: This study investigates the effects of transamidation on the toxicity of commercial wheat flour and the apparent structure, digestive level, and rheological characteristics of resultant dough and steamed bread, as a typical food model. The results show that transamidation starts at the kneading stage, as evaluated by using R5 enzyme-linked immunoassay and rat basophils. The potential toxicity of celiac disease is reduced by about 83% when 1% microbial transglutaminase (mTG), 2% l-lysine, and 1% reduced glutathione (GSH) are added, while retaining the original physical and rheological properties of wheat flour. The additional of reduced GSH also improves the in vitro protein digestibility. CONCLUSIONS: Although it cannot be a celiac disease treatment directly, this study suggests that transamidation can serve as an alternative method for reducing the gluten toxicity of wheat flour-based food products.

Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer.

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and effector tumor-infiltrating CD8+ T cells. Pharmacological inhibition of ATX, or the downstream receptor LPAR5, in combination with anti-PD-1 was sufficient to restore the antitumor immune response and efficaciously control lung tumor growth in multiple KP tumor models. Additionally, ATX was significantly correlated with inflammatory gene signatures, including a CD8+ cytolytic score in multiple lung adenocarcinoma patient data sets, suggesting that an activated tumor-immune microenvironment upregulates ATX and thus provides an opportunity for cotargeting to prevent acquired resistance to anti-PD-1 treatment. These data reveal the ATX/LPA axis as an immunosuppressive pathway that diminishes the immune checkpoint blockade response in lung cancer.

Near-Infrared Long Afterglow in Fe3+-Activated Mg2SnO4 for Self-Sustainable Night Vision.

The advent of near-infrared (NIR) afterglow in Cr3+-doped materials has stimulated considerable interest in technological applications owing to the sustainable emission of light with good penetrability. However, the development of Cr3+-free NIR afterglow phosphors with high efficiency, low cost, and precise spectral tunability is still an open question. Herein, we report a novel Fe3+-activated NIR long afterglow phosphor composed of Mg2SnO4 (MSO), in which Fe3+ ions occupy the tetrahedral [Mg-O4] and octahedral [Sn/Mg-O6] sites, giving rise to a broadband NIR emission spanning 720-789 nm. On account of energy-level alignment, the electrons released from the traps show a preferential return to the excited energy level of Fe3+ in tetrahedral sites through tunneling, leading to a single-peak NIR afterglow centered at 789 nm with a full-width at half-maximum (fwhm) of 140 nm. The high-efficiency NIR afterglow, showing a record persistent time lasting over 31 h among Fe3+-based phosphors, is demonstrated as a self-sustainable light source for night vision applications. This work not only provides a novel Fe3+-doped high-efficiency NIR afterglow phosphor for technological applications but also establishes practical guidance for rational tuning of afterglow emissions.

Sex differences in risk factors for metabolic syndrome in middle-aged and senior hospital employees: a population-based cohort study.

BACKGROUND: Several cross-sectional studies have reported risk factors for metabolic syndrome (MetS). However, these studies did not focus on sex differences in middle-aged and senior populations or employ a longitudinal design. These study design differences are important, as there are sex differences in lifestyle habits associated with MetS, and middle-aged and senior individuals have increased MetS susceptibility. Therefore, the purpose of this study was to examine whether sex differences influenced MetS risk over a ten-year follow-up period among middle-aged and senior hospital employees. METHODS: This population-based and prospective cohort study enrolled 565 participants who did not have MetS in 2012 for a ten-year repeated-measurement analysis. Data were retrieved from the hospital's Health Management Information System. Analyses included Student's t tests, χ2 tests and Cox regression. P < 0.05 indicated statistical significance. RESULTS: Male middle-aged and senior hospital employees had an elevated MetS risk (hazard ratio (HR) = 1.936, p < 0.001). Men with more than four family history risk factors had an increased risk of MetS (HR = 1.969, p = 0.010). Women who worked shift duty (HR = 1.326, p = 0.020), had more than two chronic diseases (HR = 1.513, p = 0.012), had three family history risk factors (HR = 1.623, p = 0.010), or chewed betel nuts (HR = 9.710, p = 0.002) had an increased risk of MetS. CONCLUSIONS: The longitudinal design of our study improves the understanding of sex differences in MetS risk factors in middle-aged and senior adults. A significantly elevated risk of MetS over the ten-year follow-up period was associated with male sex, shift work, the number of chronic diseases, the number of family history risk factors, and betel nut chewing. Women who chewed betel nuts had an especially increased risk of MetS. Our study indicates that population-specific studies are important for the identification of subgroups susceptible to MetS and for the implementation of hospital-based strategies.

Harsh Environmental-Tolerant and High-Performance Triboelectric Nanogenerator Based on Nanofiber/Microsphere Hybrid Membranes.

Triboelectric nanogenerator (TENG) can convert tiny mechanical energy into precious electrical energy. Constant improvements to the output performance of TENG is not only the driving force for its sustainable development, but also the key to expand its practical applicability in modern smart devices. However, most previous studies were conducted at room temperature, ignoring the influence of temperature on the output performance of TENG. Additionally, due to thermionic emission effect, the electrons transferred to a dielectric surface can be released into a vacuum after contact electrification. Therefore, TENG cannot maintain an effective electrical output under high-temperature conditions. Here, a series of high-temperature operatable flexible TENGs (HO-TENGs) based on nanofiber/microsphere hybrid membranes (FSHMs) was fabricated by electrospinning and electrospraying. The Voc of HO-TENG is 212 V, which is 2.33 times higher than that of control TENG. After 10,000 cycle stability tests, the HO-TENG shows excellent durability. Especially, this HO-TENG can maintain 77% electrical output at 70 °C compared to room temperature, showing excellent high-temperature operability. This study can not only provide a reference for the construction of advanced high-performance TENG, but also provide a certain experimental basis for efficient collection of mechanical energy in high-temperature environment and promote the application of TENG devices in harsh environments.

Effect of the Nintendo Ring Fit Adventure Exergame on Running Completion Time and Psychological Factors Among University Students Engaging in Distance Learning During the COVID-19 Pandemic: Randomized Controlled Trial.

BACKGROUND: The COVID-19 outbreak has not only changed the lifestyles of people globally but has also resulted in other challenges, such as the requirement of self-isolation and distance learning. Moreover, people are unable to venture out to exercise, leading to reduced movement, and therefore, the demand for exercise at home has increased. OBJECTIVE: We intended to investigate the relationships between a Nintendo Ring Fit Adventure (RFA) intervention and improvements in running time, cardiac force index (CFI), sleep quality (Chinese version of the Pittsburgh Sleep Quality Index score), and mood disorders (5-item Brief Symptom Rating Scale score). METHODS: This was a randomized prospective study and included 80 students who were required to complete a 1600-meter outdoor run before and after the intervention, the completion times of which were recorded in seconds. They were also required to fill out a lifestyle questionnaire. During the study, 40 participants (16 males and 24 females, with an average age of 23.75 years) were assigned to the RFA group and were required to exercise for 30 minutes 3 times per week (in the adventure mode) over 4 weeks. The exercise intensity was set according to the instructions given by the virtual coach during the first game. The remaining 40 participants (30 males and 10 females, with an average age of 22.65 years) were assigned to the control group and maintained their regular habits during the study period. RESULTS: The study was completed by 80 participants aged 20 to 36 years (mean 23.20, SD 2.96 years). The results showed that the running time in the RFA group was significantly reduced. After 4 weeks of physical training, it took females in the RFA group 19.79 seconds (P=.03) and males 22.56 seconds (P=.03) less than the baseline to complete the 1600-meter run. In contrast, there were no significant differences in the performance of the control group in the run before and after the fourth week of intervention. In terms of mood disorders, the average score of the RFA group increased from 1.81 to 3.31 for males (difference=1.50, P=.04) and from 3.17 to 4.54 for females (difference=1.38, P=.06). In addition, no significant differences between the RFA and control groups were observed for the CFI peak acceleration (CFIPA)_walk, CFIPA_run, or sleep quality. CONCLUSIONS: RFA could either maintain or improve an individual's physical fitness, thereby providing a good solution for people involved in distance learning or those who have not exercised for an extended period. TRIAL REGISTRATION: ClinicalTrials.gov NCT05227040; https://clinicaltrials.gov/ct2/show/NCT05227040.

Ni2+-Doped Garnet Solid-Solution Phosphor-Converted Broadband Shortwave Infrared Light-Emitting Diodes toward Spectroscopy Application.

Broadband shortwave infrared (SWIR) light-emitting diodes (LEDs), capable of advancing the next-generation solid-state smart invisible lighting technology, have sparked tremendous interest and will launch ground-breaking spectroscopy and instrumental applications. Nevertheless, the device performance is still suppressed by the low quantum efficiency and limited emission bandwidth of the critical phosphor layer. Herein, we report a high-performance Ni2+-doped garnet solid-solution broadband SWIR emitter centered at ∼1450 nm with a large full-width at half-maximum of ∼300 nm, thereby fabricating, for the first time, a directly excited Ni2+-doped garnet solid-solution phosphor-converted broadband SWIR LED device. A synergetic enhancement strategy, adding a fluxing agent and a charge compensator simultaneously, is proposed to deliver a more than 20-fold increase of the SWIR emission intensity and nearly 2-fold improvement of the thermal quenching behavior. The site occupation and mechanism behind the synergetic enhancement strategy are elucidated by a combination of experimental study and theoretical calculation. A prototype of the SWIR LED with a radiation flux of 1.25 mW is fabricated and utilized as an invisible SWIR light source to demonstrate the SWIR spectroscopy applications. This work not only opens a window to explore novel broadband SWIR phosphors but also provides a synergetic strategy to remarkably improve the performance of artificial SWIR LED light sources.

Targeted Covalent Inhibition of Small CTD Phosphatase 1 to Promote the Degradation of the REST Transcription Factor in Human Cells.

The repressor element-1 silencing transcription factor (REST) represses neuronal gene expression, whose dysregulation is implicated in brain tumors and neurological diseases. A high level of REST protein drives the tumor growth in some glioblastoma cells. While transcription factors like REST are challenging targets for small-molecule inhibitors, the inactivation of a regulatory protein, small CTD phosphatase 1 (SCP1), promotes REST degradation and reduces transcriptional activity. This study rationally designed a series of α,ß-unsaturated sulfones to serve as potent and selective covalent inhibitors against SCP1. The compounds inactivate SCP1 via covalent modification of Cys181 located at the active site entrance. Cellular studies showed that the inhibitors inactivate SCP1 in a time- and dose-dependent manner with an EC50 ∼1.5 µM, reducing REST protein levels and activating specific REST-suppressed genes. These compounds represent a promising line of small-molecule inhibitors as a novel lead for glioblastoma whose growth is driven by REST transcription activity.

Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation.

The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control.

Novel STAT3 small-molecule inhibitors identified by structure-based virtual ligand screening incorporating SH2 domain flexibility.

Efforts to develop STAT3 inhibitors have focused on its SH2 domain starting with short phosphotyrosylated peptides based on STAT3 binding motifs, e.g. pY905LPQTV within gp130. Despite binding to STAT3 with high affinity, issues regarding stability, bioavailability, and membrane permeability of these peptides, as well as peptidomimetics such as CJ-887, have limited their further clinical development and led to interest in small-molecule inhibitors. Some small molecule STAT3 inhibitors, identified using structure-based virtual ligand screening (SB-VLS); while having favorable drug-like properties, suffer from weak binding affinities, possibly due to the high flexibility of the target domain. We conducted molecular dynamic (MD) simulations of the SH2 domain in complex with CJ-887, and used an averaged structure from this MD trajectory as an "induced-active site" receptor model for SB-VLS of 110,000 compounds within the SPEC database. Screening was followed by re-docking and re-scoring of the top 30% of hits, selection for hit compounds that directly interact with pY + 0 binding pocket residues R609 and S613, and testing for STAT3 targeting in vitro, which identified two lead hits with good activity and favorable drug-like properties. Unlike most small-molecule STAT3 inhibitors previously identified, which contain negatively-charged moieties that mediate binding to the pY + 0 binding pocket, these compounds are uncharged and likely will serve as better candidates for anti-STAT3 drug development. IMPLICATIONS: SB-VLS, using an averaged structure from molecular dynamics (MD) simulations of STAT3 SH2 domain in a complex with CJ-887, a known peptidomimetic binder, identify two highly potent, neutral, low-molecular weight STAT3-inhibitors with favorable drug-like properties.

Genetic co-expression networks contribute to creating predictive model and exploring novel biomarkers for the prognosis of breast cancer.

Genetic co-expression network (GCN) analysis augments the understanding of breast cancer (BC). We aimed to propose GCN-based modeling for BC relapse-free survival (RFS) prediction and to discover novel biomarkers. We used GCN and Cox proportional hazard regression to create various prediction models using mRNA microarray of 920 tumors and conduct external validation using independent data of 1056 tumors. GCNs of 34 identified candidate genes were plotted in various sizes. Compared to the reference model, the genetic predictors selected from bigger GCNs composed better prediction models. The prediction accuracy and AUC of 3 ~ 15-year RFS are 71.0-81.4% and 74.6-78% respectively (rfm, ACC 63.2-65.5%, AUC 61.9-74.9%). The hazard ratios of risk scores of developing relapse ranged from 1.89 ~ 3.32 (p < 10-8) over all models under the control of the node status. External validation showed the consistent finding. We found top 12 co-expressed genes are relative new or novel biomarkers that have not been explored in BC prognosis or other cancers until this decade. GCN-based modeling creates better prediction models and facilitates novel genes exploration on BC prognosis.

Factors affecting the negative Poisson's ratio of black phosphorus and black arsenic: electronic effects.

Negative Poisson's ratio (NPR) materials (when stretched longitudinally, the thickness of these materials increases along the lateral direction) are widely used in engineering because of their good resistance to shear, denting, and fracture. Observance of a negative Poisson's ratio (NPR) in two-dimensional (2D) single-layer materials presently has two explanations. The first, from mechanical principles, is that it derives from the presence of a special structure (hinge structure), such as in single-layer black phosphorus (BP) or black arsenic (ß-As). The second, from electronic effects, is that it derives from (non-hinge-like) planar honeycomb structures and transition-metal dichalcogenides, MX2. Through first-principle calculations, we show that 2D single-layer materials with a hinge structure also have distinct electronic effects, similar to those observed from 2D planar honeycomb materials. Under strain, electronic effects of Px orbitals lead to the inherent NPR of the 2D single-layer material with a hinge structure. We discuss the influencing factors of the hinge structure on the NPR and demonstrate that the electronic effects inside the hinge structure are the fundamental factor in determining the inherent NPR.