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Background/purposeDyslipidemia, a hallmark of metabolic syndrome (MetS), contributes to atherosclerotic and cardiometabolic disorders. Due to days-long analysis, current clinical procedures for cardiotoxic blood lipid monitoring are unmet. This study used AI-assisted attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy to identify MetS and precisely quantify multiple blood lipid levels with a blood sample of 0.5 µl and the assaying time is approximately 10 minutes.MethodsATR-FTIR spectroscopy with 1738 data points in the spectral range of 4000-650 cm-1 was used to analyze the blood samples. An adaptive synthetic technique was used to establish a prevalence-balanced dataset. LDL-C, HDL-C, TG, VLDL-C, and cholesterol levels were defined as the predicted targets of lipid absorption profiles. Linear regression (LR), gradient boosting regression tree (GBT), and histogram-based gradient boosting regression tree (HGBTR) were used to train the models. Lipid profile value prediction was evaluated using R2 and MAE, whereas MetS prediction was evaluated using area under the ROC curve.ResultsA total of 150 blood samples from 25 individuals without MetS and 25 with MetS yielded 491 spectral measurements. In the regression models, HGBT best predicted the targets of TG, CHOL, HDL-C, LDL-C, and VLDL-C with R2 values of 0.854 (0.12), 0.684 (0.08), 0.758 (0.10), and 0.419 (0.11), respectively. The classification model with the greatest AUC was RF (0.978), followed by HGBT (0.972) and GBT (0.967).ConclusionThe results of this study revealed that predicting MetS and determining blood lipid levels with high R2 values and limited errors are feasible for monitoring during therapy and intervention.

Abstract Photothermoelectric (PTE) detectors combine photothermal and thermoelectric conversion, surmounting material band gap restrictions and limitations related to matching light wavelengths, have been widely used in telecommunication band detection. Two‐dimensional (2D) materials with gate‐tunable Seebeck coefficient can induce the generation of photothermal currents under illumination by the asymmetric Seebeck coefficient, making them promising candidate for PTE detectors in the telecommunication band. In this work, we report that a newly explored van der Waals (vdW) layered material, SnP2Se6, possessing excellent field regulation capabilities and behaviors as an ideal candidate for PTE detector implementation. With the assistance of temperature‐dependent Raman characterization, the suspended atomic thin SnP2Se6 nanosheets reveal thickness‐dependent thermal conductivity of 1.4–5.7 W m−1 K−1 at room temperature. The 2D SnP2Se6 demonstrates high Seebeck coefficient (S) and power factor (PF), which are estimated to be −506 μV K−1 and 207 μW m−1 K−2, respectively. By effectively modulating the SnP2Se6 localized carrier concentration, which in turn leads to inhomogeneous Seebeck coefficients, the designed dual‐gate PTE detector with 2D SnP2Se6 channel demonstrates wide spectral photoresponse in telecommunication bands, yielding high responsivity (R = 1.2 mA W−1) and detectivity (D* = 6 × 109 Jones) under 1550 nm light illumination. Our findings provide a new material platform and device configuration for the telecommunication band detection.

Patterns of disease and therapeutic responses vary widely among patients with autoimmune glomerulonephritis. This study introduces groundbreaking personalized infrared (IR)-based diagnostics for real-time monitoring of disease status and treatment responses in lupus nephritis (LN). We have established a relative absorption difference (RAD) equation to assess characteristic spectral indices based on the temporal peak heights (PHs) of two characteristic serum absorption bands: ν1 as the target signal and ν2 as the PH reference for the ν1 absorption band, measured at each dehydration time (t) during dehydration. The RAD gap (Ψ), defined as the difference in the RAD values between the initial and final stages of serum dehydration, enables the measurement of serum levels of IgG glycosylation (ν1 (1030 cm−1), ν2 (1171 cm−1)), serum lactate (ν1 (1021 cm−1), ν2 (1171 cm−1)), serum hydrophobicity (ν1 (2930 cm−1), ν2 (2960 cm−1)), serum hydrophilicity (ν1 (1550 cm−1), ν2 (1650 cm−1)), and albumin (ν1 (1400 cm−1), ν2 (1450 cm−1)). Furthermore, this IR-based assay incorporates an innovative algorithm and our proprietary iPath software (ver. 1.0), which calculates the prognosis prediction function (PPF, Φ) from the RAD gaps of five spectral markers and correlates these with conventional clinical renal biomarkers. We propose that this algorithm-assisted, IR-based approach can augment the patient-centric care of LN patients, particularly by focusing on changes in serum IgG glycosylation.

Introduction: Few real-world studies have investigated drug-drug interactions (DDIs) involving non-vitamin-K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation (NVAF). The interactions encompass drugs inducing or inhibiting cytochrome P450 3A4 and permeability glycoprotein. These agents potentially modulate the breakdown and elimination of NOACs. This study investigated the impact of DDIs on thromboembolism in this clinical scenario. Method: Patients who had NVAF and were treated with NOACs were selected as the study cohort from the National Health Insurance Research Database of Taiwan. Cases were defined as patients hospitalised for a thromboembolic event and who underwent a relevant imaging study within 7 days before hospitalisa-tion or during hospitalisation. Each case was matched with up to 4 controls by using the incidence density sampling method. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer or inhibitor or both with NOACs was identified. The effects of these interactions on the risk of thromboembolic events were examined with univariate and multivariate conditional logistic regressions. Results: The study cohort comprised 60,726 eligible patients. Among them, 1288 patients with a thromboembolic event and 5144 matched control patients were selected for analysis. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer resulted in a higher risk of thromboembolic events (adjusted odds ratio [AOR] 1.23, 95% confidence interval [CI] 1.004–1.51). Conclusion: For patients with NVAF receiving NOACs, the concurrent use of cytochrome P450 3A4/ permeability glycoprotein inducers increases the risk of thromboembolic events.

Abstract Neuro-inspired vision systems hold great promise to address the growing demands of mass data processing for edge computing, a distributed framework that brings computation and data storage closer to the sources of data. In addition to the capability of static image sensing and processing, the hardware implementation of a neuro-inspired vision system also requires the fulfilment of detecting and recognizing moving targets. Here, we demonstrated a neuro-inspired optical sensor based on two-dimensional NbS2/MoS2 hybrid films, which featured remarkable photo-induced conductance plasticity and low electrical energy consumption. A neuro-inspired optical sensor array with 10 × 10 NbS2/MoS2 phototransistors enabled highly integrated functions of sensing, memory, and contrast enhancement capabilities for static images, which benefits convolutional neural network (CNN) with a high image recognition accuracy. More importantly, in-sensor trajectory registration of moving light spots was experimentally implemented such that the post-processing could yield a high restoration accuracy. Our neuro-inspired optical sensor array could provide a fascinating platform for the implementation of high-performance artificial vision systems.

Abstract Two-dimensional (2D) layered semiconductors with nonlinear optical (NLO) properties hold great promise to address the growing demand of multifunction integration in electronic-photonic integrated circuits (EPICs). However, electronic-photonic co-design with 2D NLO semiconductors for on-chip telecommunication is limited by their essential shortcomings in terms of unsatisfactory optoelectronic properties, odd-even layer-dependent NLO activity and low NLO susceptibility in telecom band. Here we report the synthesis of 2D SnP2Se6, a van der Waals NLO semiconductor exhibiting strong odd-even layer-independent second harmonic generation (SHG) activity at 1550 nm and pronounced photosensitivity under visible light. The combination of 2D SnP2Se6 with a SiN photonic platform enables the chip-level multifunction integration for EPICs. The hybrid device not only features efficient on-chip SHG process for optical modulation, but also allows the telecom-band photodetection relying on the upconversion of wavelength from 1560 to 780 nm. Our finding offers alternative opportunities for the collaborative design of EPICs.

It is critical to understand the factors that are associated with nasopharyngeal carcinoma (NPC) progression, metastasis and response to therapy. Here, the authors analyse primary and metastatic NPC samples using bulk and single-cell sequencing, and find two distinct evolutionary routes that lead to metastasis.

Abstract Global declines in shorebird populations resulting from foraging habitat loss have been recently reported, and the situation within the East Asian‐Australasian Flyway (EAAF) is particularly concerning. Despite previous studies that analyzed the foraging niches of shorebirds worldwide, the dietary niche dynamics of shorebirds coexisting in Asia are very poorly understood. This study is therefore among the early few that aim to unveil the trophic organization of shorebirds in a subtropical wetland within the EAAF which is vital for species conservation. Our study first determined the dietary spectra of more than 10 shorebird species, such as Calidris ferruginea (near threatened), Charadrius leschenaultii, and Pluvialis squatarola, by applying DNA metabarcoding with 18S and COI markers to fecal DNA. The diet of Tringa stagnatilis was also characterized, which was previously undescribed. Shorebirds that occurred in the wetland consumed a variety of food items, primarily a high abundance of malacostracans, mollusks, annelids, insects, and some arachnids. Different proportions of plant materials were also detected in many shorebird species. Using the data, we then revealed clear patterns of inter‐ and intraspecific variations between these shorebirds. Importantly, we specifically compared the similarities of the spring diets among seven sympatric shorebird species. We found that the dietary compositions of the seven species have segregated from each other to varying levels, but the many similar taxa we identified in the diets among these shorebirds imply that these populations of shorebirds could be competing at different levels. Thus, any reductions in the abundance and diversity of these important food resources would likely intensify their inter‐ and intraspecific competition, and simultaneously threaten the survival of multiple species. With these findings, conservation measures must be taken to protect and monitor the vital food resources for these energy‐deprived shorebirds during migration.

Abstract Neuroendocrine neoplasm (NEN) is a common gastrointestinal (GI) tract tumor divided into the neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC) according to mitosis and Ki-67 index. However, the objective discordance between interobserver may cause unsuitable diagnosis and misleading treatment. Nowadays, aberrant glycosylation of glycoconjugates inducing further populations of elongated complex oligosaccharide covalent attached to glycoconjugates anchored in the cell membrane by neo-synthesis of cancer-associated alteration of carbohydrate determinants were observed during cancer development. This study aimed to demonstrate the wax physisorption kinetics coupled with Fourier transform infrared (WPK-FTIR) imaging between NET and NEC in the rectum, colon, and stomach by utilizing two wax reagents (beeswax and paraplast) as glycan adsorbents for physical binding glycans of glycoconjugates based on dipole-induced dipole interaction. Results showed greater physisorption with beeswax than that of paraplast, suggesting highly populated elongated glycans of glycoconjugates adhering onto the tumor surfaces of NETs than that of adjacent benign mucosa in the rectum and colon. Besides, the WPK results of gastric NEN tissue sections showed a higher infrared absorbance ratio of beeswax-remnant to paraplast-remnant remains onto the tissue sections referring to a higher population of elongated glycans in gastric NET as compared with that of gastric NEC. Based on our findings, different anatomical locations could share similar phenomena with minor variance. In conclusion, WPK-FTIR imaging may have the potential to be employed as an alternative diagnostic method in GI NENs in the future.

Summary: Background: Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens. Methods: This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381. Findings: Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6–55.4) and the DCR was 77.8% (90% CI, 56.1–92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0–not reach), and the median PFS was 7.2 months (90% CI, 4.4–13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3–4 major epistaxis, and they were cured by nasal packing and vascular embolization. Interpretation: Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings. Funding: Jiangsu Hengrui Pharmaceutical Co., Ltd.

Peptide conformational imprints (PCIs) offer a promising perspective to directly generate binding sites for preserving enzymes with high catalytic activity and stability. In this study, we synthesized a new chiral cross-linker cost-effectively for controlling the matrix morphology of PCIs on magnetic particles (PCIMPs) to stabilize their recognition capability. Meanwhile, based on the flank part of the sequences on papain (PAP), three epitope peptides were selected and synthesized. Molecularly imprinted polymers (MIPs) were then fabricated in the presence of the epitope peptide using our new cross-linker on magnetic particles (MPs) to generate PCIMPs. PCIMPs were formed with helical cavities that complement the PAP structure to adsorb specifically at the targeted position of PAP. PCIMPs65–79 were found to have the best binding parameters to the PAP with Kd = 0.087 μM and Bmax = 4.56 μM. Upon esterification of N-Boc-His-OH, proton nuclear magnetic resonance (1H-NMR) was used to monitor the yield of the reaction and evaluate the activity of PAP/PCIMPs. The kinetic parameters of PAP/PCIMPs65–79 were calculated as Vmax = 3.0 μM s−1, Km = 5 × 10−2 M, kcat = 1.1 × 10–1 s−1, and kcat/Km = 2.2 M−1 s−1. In addition, PAP is bound tightly to PCIMPs to sustain its activity after four consecutive cycles.

Background: Studies of local therapy (LT) to metastatic foci from nasopharyngeal carcinoma (NPC) are inconsistent and controversial. Here, we aimed to explore the survival benefit of LT directed at metastatic foci from NPC. Methods: A retrospective analysis was conducted in NPC patients with liver, lung, and/or bone metastases. The postmetastatic overall survival (OS) rate was analyzed using the Kaplan–Meier method and compared by the log-rank test. Multivariate analysis was performed using the Cox hazard model. Subgroup analyses evaluating the effect of LT were performed for prespecified covariates. Propensity score matching was applied to homogenize the compared arms. Results: Overall, 2041 of 2962 patients were eligible for analysis. At a median follow-up of 43.4 months, the 5-year OS improved by an absolute difference of 14.6%, from 46.2% in the LT group versus 31.6% in the non-LT group, which led to a hazard ratio of 0.634 for death ( p 60 Gy was found to yield more survival benefit than that of BED ⩽ 60 Gy. Conclusions: The addition of LT directed at metastasis has demonstrated an improvement to OS compared with non-LT group in the present matched-pair study, especially for patients with liver and/or lung metastases.

Avians have evolved many different modes of flying as well as various types of feathers for adapting to varied environments. However, the protein content and ratio of protein secondary structures (PSSs) in mature flight feathers are less understood. Further research is needed to understand the proportions of PSSs in feather shafts adapted to various flight modes in different avian species. Flight feathers were analyzed in chicken, mallard, sacred ibis, crested goshawk, collared scops owl, budgie, and zebra finch to investigate the PSSs that have evolved in the feather cortex and medulla by using nondestructive attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). In addition, synchrotron radiation-based, Fourier transform infrared microspectroscopy (SR-FTIRM) was utilized to measure and analyze cross-sections of the feather shafts of seven bird species at a high lateral resolution to resolve the composition of proteins distributed within the sampled area of interest. In this study, significant amounts of α-keratin and collagen components were observed in flight feather shafts, suggesting that these proteins play significant roles in the mechanical strength of flight feathers. This investigation increases our understanding of adaptations to flight by elucidating the structural and mechanistic basis of the feather composition.

The β-sheet is one of the common protein secondary structures, and the aberrant aggregation of β-sheets is implicated in various neurodegenerative diseases. Cross-strand interactions are an important determinant of β-sheet stability. Accordingly, both diagonal and lateral cross-strand interactions have been studied. Surprisingly, diagonal cross-strand ion-pairing interactions have yet to be investigated. Herein, we present a systematic study on the effects of charged amino acid side-chain length on a diagonal ion-pairing interaction between carboxylate- and ammonium-containing residues in a β-hairpin. To this end, 2D-NMR was used to investigate the conformation of the peptides. The fraction folded population and the folding free energy were derived from the chemical shift data. The fraction folded population for these peptides with potential diagonal ion pairs was mostly lower compared to the corresponding peptide with a potential lateral ion pair. The diagonal ion-pairing interaction energy was derived using double mutant cycle analysis. The Asp2-Dab9 (Asp: one methylene; Dab: two methylenes) interaction was the most stabilizing (−0.79 ± 0.14 kcal/mol), most likely representing an optimal balance between the entropic penalty to enable the ion-pairing interaction and the number of side-chain conformations that can accommodate the interaction. These results should be useful for designing β-sheet containing molecular entities for various applications.