Orbital Magneto-Nonlinear Anomalous Hall Effect in Kagome Magnet Fe_{3}Sn_{2}.

It has been theoretically predicted that perturbation of the Berry curvature by electromagnetic fields gives rise to intrinsic nonlinear anomalous Hall effects that are independent of scattering. Two types of nonlinear anomalous Hall effects are expected. The electric nonlinear Hall effect has recently begun to receive attention, while very few studies are concerned with the magneto-nonlinear Hall effect. Here, we combine experiment and first-principles calculations to show that the kagome ferromagnet Fe_{3}Sn_{2} displays such a magneto-nonlinear Hall effect. By systematic field angular and temperature-dependent transport measurements, we unambiguously identify a large anomalous Hall current that is linear in both applied in-plane electric and magnetic fields, utilizing a unique in-plane configuration. We clarify its dominant orbital origin and connect it to the magneto-nonlinear Hall effect. The effect is governed by the intrinsic quantum geometric properties of Bloch electrons. Our results demonstrate the significance of the quantum geometry of electron wave functions from the orbital degree of freedom and open up a new direction in Hall transport effects.

Oriented Antibody-Assembled Metal-Organic Frameworks for Persistent Wearable Sweat Cortisol Detection.

The level of cortisol can reflect people's psychological stress, help diagnose adrenal gland diseases, and is also related to several mental diseases. In this study, we developed a cortisol monoclonal antibody-oriented approach to modify an immunosensor for wearable label-free and persistent sweat cortisol detection. On such an antibody-oriented immunosensor, the fragment crystallizable (Fc) region is partially inserted within the metal-organic framework (MOF), and antibody-binding regions of the cortisol monoclonal antibody (Cmab) were exposed on the MOF surface via selective growth and self-assembly. Such ordered and oriented embedding of antibodies in the MOF resulted in excellent antibody activity and improved stability and antigen-binding capacity. We also engineered the full integrated system for on-body sweat cortisol biosensing performance in several volunteers, and the results indicated that this wearable sensor is suitable for practical cortisol detection with a good linear detection range from 1 pg/mL to 1 µg/mL with a lower limit of detection of 0.26 pg/mL. Moreover, the wearable sensor demonstrated good persistence in detecting cortisol, with only 4.1% decay after 9 days of storage. The present work represents a simple oriented antibody assembling approach to improve the stability of antibodies, providing an important step toward long-term continuous sweat biomarker detection.

Convenient synthesis of N-alkyl-3,1-benzoxazin-2-ones from carbamate protected anthranil aldehydes and ketones via one-step alkylation/alkoxy rearrangement.

A practical and step-economical protocol was developed to prepare N-alkyl-3,1-benzoxazin-2-one derivatives from anthranil aldehydes and ketones via one-step alkylation/alkoxy rearrangement, where three new chemical bonds and one ring were constructed in a single step. Control studies revealed a stepwise mechanism and that the alkoxy rearrangement was an intermolecular process.

Description and phylogenetic analysis of the complete mitochondrial genome in Eulaelaps silvestris provides new insights into the molecular classification of the family Haemogamasidae.

In this study, the mitochondrial genome of Eulaelaps silvestris, which parasitizes Apodemus chevrieri, was sequenced and assembled to fill the gap in understanding the molecular evolution of the genus Eulaelaps. The E. silvestris mitochondrial genome is a double-stranded DNA molecule with a length of 14 882 bp, with a distinct AT preference for base composition and a notably higher AT content than GC content. The arrangement between genes is relatively compact, with a total of 10 gene intergenic regions and 12 gene overlap regions. All protein-coding genes had a typical ATN initiation codon, and only 2 protein-coding genes had an incomplete termination codon T. Out of the 13 protein-coding genes, the 5 most frequently used codons ended in A/U, with only 1 codon ending in G/C had an relative synonymous codon usage value >1. Except for trnS1 and trnS2, which lacked the D arm, all other tRNAs were able to form a typical cloverleaf structure; and there were a total of 38 mismatches in the folding process of tRNA genes. Unlike the gene arrangement order of the arthropod hypothetical ancestor, the E. silvestris mitochondrial genome underwent fewer rearrangements, mainly near tRNA genes and control regions. Both the maximum likelihood tree and the Bayesian tree showed that the family Haemogamasidae is most closely related to the family Dermanyssidae. The results not only provide a theoretical basis for studying the phylogenetic relationships of the genus Eulaelaps, but also provide molecular evidence that the family Haemogamasidae does not belong to the subfamily Laelapidae.

Pharmacokinetics, mass balance, and metabolism of [14C]TPN171, a novel PDE5 inhibitor, in humans for the treatment of pulmonary arterial hypertension.

TPN171 is a novel phosphodiesterase-5 (PDE5) inhibitor used to treat pulmonary arterial hypertension (PAH) and erectile dysfunction (ED), which currently is undergoing phase II clinical trials in China. In this single-center, single-dose, nonrandomized, and open design study, radiolabeled [14C]TPN171 was used to investigate the metabolic mechanism, pharmacokinetic characteristics, and clearance pathways of TPN171 in 6 healthy Chinese male volunteers. Each volunteer was administered a single oral suspension of 10 mg (100 µCi) of [14C]TPN171. We found that TPN171 was absorbed rapidly in humans with a peak time (Tmax) of 0.667 h and a half-life (t1/2) of approximately 9.89 h in plasma. Excretion of radiopharmaceutical-related components was collected 216 h after administration, accounting for 95.21% of the dose (46.61% in urine and 48.60% in feces). TPN171 underwent extensive metabolism in humans. Twenty-two metabolites were detected in human plasma, urine, and feces using a radioactive detector combined with a high-resolution mass spectrometer. According to radiochromatograms, a glucuronide metabolite of O-dealkylated TPN171 exceeded 10% of the total drug-related components in human plasma. However, according to the Food and Drug Administration (FDA) guidelines, no further tests are needed to evaluate the safety of this metabolite because it is a phase II metabolite, but the compound is still worthy of attention. The main metabolic biotransformation of TPN171 was mono-oxidation (hydroxylation and N-oxidation), dehydrogenation, N-dealkylation, O-dealkylation, amide hydrolysis, glucuronidation, and acetylation. Cytochrome P450 3A4 (CYP3A4) mainly catalyzed the formation of metabolites, and CYP2E1 and CYP2D6 were involved in the oxidative metabolism of TPN171 to a lesser extent. According to the incubation data, M1 was mainly metabolized to M1G by UDP-glucuronosyltransferase 1A9 (UGT1A9), followed by UGT1A7 and UGT1A10.

The complete mitochondrial genome of Eulaelaps huzhuensis (Mesostigmata: Haemogamasidae).

Some mites of the family Haemogamasidae can transmit a variety of zoonotic diseases and have important public health and safety implications. Currently, however, little attention has been paid to molecular data of Haemogamasidae species, limiting our understanding of their evolutionary and phylogenetic relationships. In this study, the complete mitochondrial genome of Eulaelaps huzhuensis was determined for the first time, and its genomic information was analyzed in detail. The mitochondrial genome of E. huzhuensis is 14,872 bp in length with 37 genes and two control regions. The base composition showed a distinct AT preference. Twelve protein-coding genes have a typical ATN as the start codon, and three protein-coding genes have incomplete stop codons. During the folding of tRNA genes, a total of 30 mismatches occurred, and three tRNA genes had an atypical cloverleaf secondary structure. The order of the E. huzhuensis mitochondrial genome arrangement is a new type of rearrangement in Mesostigmata. The phylogenetic analysis confirmed that the family Haemogamasidae is a monophyletic branch and does not belong to a subfamily of the Laelapidae. Our results lay the foundation for subsequent studies on the phylogeny and evolutionary history of the family Haemogamasidae.

Visible-Light-Switchable Tellurium-Based Chalcogen Bonding: Photocontrolled Anion Binding and Anion Abstraction Catalysis.

Exploring new noncovalent bonding motifs with reversibly tunable binding affinity is of fundamental importance in manipulating the properties and functions of supramolecular self-assembly systems and materials. Herein, for the first time, we demonstrate a unique visible-light-switchable telluro-triazole/triazolium-based chalcogen bonding (ChB) system in which the Te moieties are connected by azobenzene cores. The binding strengths between these azo-derived ChB receptors and the halide anions (Cl- , Br- ) could be reversibly regulated upon irradiation by visible light of different wavelengths. The cis-bidentate ChB receptors exhibit enhanced halide anion binding ability compared to the trans-monodentate receptors. In particular, the telluro-triazolium-based ChB receptor can achieve both high and significantly photoswitchable binding affinities for halide anions, which enable it to serve as an efficient photocontrolled organocatalyst for ChB-assisted halide abstraction in a Friedel-Crafts alkylation benchmark reaction.

Prophylactic Effect of Simultaneous Placement of Mesh on Incidence of Parastomal Hernia After Miles' Surgical Resection of Colorectal Cancer: A Prospective Study.

INTRODUCTION: To assess the prophylactic effect of simultaneous placement of mesh and the incidence of parastomal hernia (PSH) after abdominoperineal resection of rectal cancer. METHODS: This study included real-world data of 56 surgically resected patients with colorectal cancer who were consecutively assigned to two groups: control (no mesh, n = 32) and experimental (received mesh, n = 24). An artificial patch was placed under the tunica vaginalis of rectus abdominis for patients in the experimental group, whereas those in the control group received routine sigmoidostomy. The median follow-up time was >20 mo. The difference in hazards function was analyzed by cox regression analysis. The Kaplan-Meir analysis was used to determine the survival curves. A P value of <0.05 was considered as significant. RESULTS: The postoperative incidence rate of PSH was lower in the experimental (41.7%) group than in the control group (71.9%; P = 0.045). The PSH postoperative time in the experimental group was significantly delayed compared to the control group (48 mo versus 10 mo; P < 0.001). The risk of progression from H1 to H2 was less in the experimental group compared to the control group (49.28% versus 60.86%; P = 0.14). CONCLUSIONS: Prophylactic mesh placement significantly prolonged postoperative time for the recurrence of PSH. The incidence of recurrence of H2 (severe PSH) requiring secondary surgical repair was also reduced.

Enlarging Sensitivity of Fluorescence Intensity Ratio-Type Thermometers by the Interruption of the Energy Transfer from a Sensitizer to an Activator.

The occurrence of energy transfer (ET) would enhance the luminescence of the activator but sacrifice that of the sensitizer. However, the novel Sm3+-doped Ca2TbSn2Al3O12 (CTSAO) phosphor reported here seems to be an exception. In the series of CTSAO:xSm3+ phosphors investigated, something unexpected occurs; the activator, Sm3+, did not gain any energy compensation from the sensitizer, Tb3+, when temperature increases. Instead, when the loss of Sm3+ luminescence accelerates, simultaneously, the loss of Tb3+ luminescence accordingly alleviates. By careful calculations on the ET efficiency of the CTSAO:0.06Sm3+ phosphor at different temperatures, it is surprisingly found that the efficiency keeps decreasing as temperature increases. It means that the Tb3+-Sm3+ energy transfer is capable of being interrupted by an increasing temperature. By simulation, it is found that the occurrence of thermal interruption of energy transfer benefits the achievement of a higher temperature sensing sensitivity. In this sense, making use of the thermal interruption of energy transfer could become a novel route for further design of the fluorescence intensity ratio-type luminescence thermometers.

Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.

Clinical efficacy and feasibility of laser correction technology with an ordinary laser pen and surgical instrument box in open-wedge high tibial osteotomy.

BACKGROUND: The clinical outcomes of open-wedge high tibial osteotomy (OWHTO) for medial knee osteoarthritis primarily depend on the corrective precision. The present study aimed to determine the efficacy and feasibility of laser correction technology with an ordinary laser pen and surgical instrument box. METHODS: This prospective and randomized trial included 71 patients randomly divided into laser (n = 36) and traditional groups (n = 35). In the laser group, the hip centre, knee (Fujisawa point), and ankle centre were located preoperatively using the surgical instrument box lid. The leg was aligned with an ordinary laser pen. In the traditional group, the lower limb alignment was corrected by a metal cable. Radiation exposure, operative time, and rate of outliers (lower limb force line does not pass through 62-66% of the lateral tibial plateau) were evaluated. The visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were recorded. After 24 months, the femoral tibial angle (FTA), medial proximal tibial angle (MPTA), and posterior slope angle (PSA), were recorded. The Kaplan-Meier method was used to evaluate the survival time of affected knees, and postoperative complications were recorded. RESULTS: The radiation exposure, operative time and rate of outliers were lower in the laser correction group (P < 0.05). Six months postoperatively, the VAS and WOMAC scores were significantly improved in both groups (P < 0.001). At 24 months, the FTA, MPTA, and PSA were corrected in both groups (P < 0.001). There were no differences in the postoperative knee survival time from OWHTO to knee arthroplasty between the groups or postoperative complications (P = 0.53; P = 0.61). CONCLUSIONS: Laser correction technology can effectively reduce radiation exposure, the operative time, and the rate of outliers (trial identification number (retrospectively registered): ChiCTR2200060480; date of register: 03/06/2022).

The predictive value of the Singh index for the risk of InterTAN intramedullary fixation failure in elderly patients with intertrochanteric fractures.

BACKGROUND: To investigate the predictive value of the Singh index for the risk of InterTAN intramedullary fixation failure in elderly patients with intertrochanteric fracture to guide clinical treatment. METHODS: A total of 360 patients were divided into the Singh (I ~ II) (n = 120), Singh (III ~ IV) (n = 120) and Singh (V ~ VI) (n = 120) groups. Visual analog scale (VAS) and Harris scores were recorded at 1, 6, 12, 18 and 24 months after the operation. The correlation between the Singh index and the T-score of the total hip and femoral neck was analyzed. Logistic regression was used to analyze the relationship between the Singh index and internal fixation failure; the types of internal fixation failure were also analyzed. RESULTS: The Harris scores of the Singh (I ~ II) group were lower than those of the Singh (III ~ IV) and Singh (V ~ VI) groups 12, 18 and 24 months after surgery (P < 0.05). The Singh index was significantly correlated with the T-score of the total hip and femoral neck (P = 0.00, r = 0.89; P = 0.00, r = 0.83). The Singh (I ~ II) group had the lowest internal fixation survival rate within 24 months (P = 0.01). The Singh index was an independent predictor of internal fixation failure (P < 0.05). Lag screw cutting-out was the main type of internal fixation failure in the three groups (P = 0.00). CONCLUSION: The Singh index is significantly correlated with the bone mineral density of the femoral neck and total hip. The Singh (I ~ II) group had lower Harris scores and a lower internal fixation survival rate than the other two groups. The Singh index is an independent predictor of internal fixation failure, especially lag screw cutting-out, after InterTAN fixation.

A Report of Chigger Mites on the Striped Field Mouse, Apodemus agrarius, in Southwest China.

Based on the field investigations in 91 investigation sites (counties) in southwest China between 2001 and 2019, the present paper reported the chigger mites on A. agrarius mice in southwest China for the first time by using a series of statistical methods. From 715 striped field mice captured in 28 of 91 investigated sites, only 255 chiggers were collected, and they were identified as 14 species, 6 genera in 3 subfamilies under 2 families. Of 715 A. agrarius mice, only 24 of them were infested with chigger mites with low overall prevalence (PM=3.4%), overall mean abundance (MA=0.36 mites/host) and overall mean intensity (MI=10.63 mites/host). The species diversity and infestation of chiggers on A. agrarius were much lower than those previously reported on some other rodents in southwest China. On a certain species of rodent, A. agrarius mouse in southwest China seems to have a very low susceptibility to chigger infestations than in other geographical regions. Of 14 chigger species, there were 3 dominant species, Leptotrombidium sialkotense, L. rupestre and Schoengastiella novoconfuciana, which were of aggregated distribution among different individuals of A. agrarius hosts. L. sialkotense, one of 6 main vectors of scrub typhus in China, was the first dominant on A. agrarius. The species similarity of chigger mites on male and female hosts was low with CSS=0.25, and this reflects the sex-bias of different genders of A. agrarius mice in harboring different chigger species.

[Spinal cord magnetic resonance imaging: methods and applications].

Spinal cord magnetic resonance imaging (MRI) is an advanced imaging technique (mainly in the cervical cord) and has been gradually used in basic scientific research such as human sensation and motor function, and clinical applications such as spinal cord injury, myelitis, and chronic pain, etc. The development of spinal cord MRI is still at the early stage compared with brain MRI and limited by the current MRI technology and data analysis methods. This review focuses on the methods and applications of spinal cord MRI technology in the basic research fields of cognitive neuroscience and clinical application. Firstly, we will introduce the imaging principle, methods, measurement standards, and applications of most commonly used multimodal spinal cord MRI techniques, including quantitative spinal cord MRI (such as structural, diffusion, spectroscopy, myelin water, magnetization transfer, and chemical exchange saturation transfer imaging, etc.) and spinal functional MRI (fMRI). Secondly, we will discuss the technical challenges and possible solutions of spinal cord MRI data processing from the three dimensions of denoising, data processing pipeline optimization, and repeatability and reliability. Finally, we will discuss the application status and development prospects of spinal cord MRI.

Plasmonic Hot Electrons from Oxygen Vacancies for Infrared Light-Driven Catalytic CO2 Reduction on Bi2 O3-x.

Current plasmonic photocatalysts are mainly based on noble metal nanoparticles and rarely work in the infrared (IR) light range. Herein, cost-effective Bi2 O3-x with oxygen vacancies was formed in situ on commercial bismuth powder by calcination at 453.15 K in atmosphere. Interestingly, defects introduced into Bi2 O3-x simultaneously induced a localized surface plasmon resonance (LSPR) in the wavelength range of 600-1400 nm and enhanced the adsorption for CO2 molecules, which enabled efficient photocatalysis of CO2 -to-CO (ca. 100 % selectivity) even under low-intensity near-IR light irradiation. Significantly, the apparent quantum yield for CO evolution at 940 nm reached 0.113 %, which is approximately 4 times that found at 450 nm. We also showed that the unique LSPR allows for the realization of a nearly linear dependence of photocatalytic CO production rate on light intensity and operating temperature. Finally, based on an IR spectroscopy study, an oxygen-vacancy induced Mars-van Krevlen mechanism was proposed to understand the CO2 reduction reactions.

Constructing ultra-sensitive dual-mode optical thermometers: Utilizing FIR of Mn4+/Eu3+ and lifetime of Mn4+ based on double perovskite tellurite phosphor.

A strategy of optical temperature sensing was developed by using various thermal quenching of Mn4+ and Eu3+ for double perovskite tellurite phosphor in optical thermometers. Herein, SrGdLiTeO6 (SGLT): Mn4+,Eu3+ phosphors were synthesized by a high-temperature solid-state reaction method. The temperature-dependent emission spectra indicated that two distinguishable emission peaks originated from Eu3+ and Mn4+ exhibited significantly diverse temperature responses. Therefore, optical thermometers with a dual-mode mechanism were designed by employing a fluorescence intensity ratio (FIR) of Mn4+ (2Eg→4A2g) and Eu3+ (5D0→7F1,2) and the decay lifetime of Mn4+ as the temperature readouts. The temperature sensing of the phosphors ranging from 300 to 550 K were studied. The maximum relative sensitivities (Sr) are obtained as 4.9% K-1 at 550 K. Meanwhile, the 695 nm emission of Mn4+ possessed a temperature-dependent decay lifetime with Sr of 0.229% K-1 at 573 K. Relevant results demonstrate the SrGdLiTeO6:Mn4+, Eu3+ phosphor as an optical thermometer candidate and also provide constructive suggestions and guidance for constructing high-sensitivity dual-mode optical thermometers.

Synthesis of Tri(4-formylphenyl) Phosphonate Derivatives as Recyclable Triple-Equivalent Supports of Peptide Synthesis.

To seek the novel application of organophosphorus compounds, the designed tri(4-formylphenyl) phosphonate (TFP) derivatives were successfully synthesized herein, which were used as C-terminal protecting groups of amino acid or greener triple-equivalent supports in liquid-phase peptide synthesis (LPPS). Through the support-aided precipitation effect of TFP derivatives, the peptide intermediates during peptide synthesis were separated and collected via rapid precipitation and facile filtration without chromatographic purification. Furthermore, the TFP derivative support can be directly recycled for reuse without further regeneration after being sheared from the target peptide.

Gate-tunable high magnetoresistance in monolayer Fe3GeTe2 spin valves.

Ferromagnetic order in two-dimensional (2D) van der Waals crystals has been attracting much attention recently. Remarkably, room temperature metallic ferromagnetism is realized in 2D Fe3GeTe2. Here we design a monolayer (ML) Fe3GeTe2 spin-valve device by attaching two ends to ferromagnetic electrodes and applying a magnetic field to these ferromagnetic electrodes. We investigate the spin-involved transport characteristics of such a spin valve by using ab initio quantum transport simulation. A high magnetoresistance of ∼390% is obtained and significantly increased to 450-510% after the gates are introduced. The magnetoresistance of the ML Fe3GeTe2 spin valve is insensitive to the strain modulation. Our study provides a potential option for magnetic storage applications and will motivate further studies in spintronics based on this class of materials.

Impairment of mitochondrial dynamics involved in iron oxide nanoparticle-induced dysfunction of dendritic cells was alleviated by autophagy inhibitor 3-methyladenine.

Iron oxide nanoparticles are nanomaterials that are used extensively in the biomedical field, but they are associated with adverse effects, including mitochondrial toxicity. Mitochondrial homeostasis is achieved through dynamic stability based on two sets of antagonistic balanced processes: mitochondrial biogenesis and degradation as well as mitochondrial fission and fusion. In this study, we showed that PEG-COOH-coated Fe3 O4 (PEG-Fe3 O4 ) nanoparticles induced mitochondrial instability in dendritic cells (DCs) by impairing mitochondrial dynamics due to promotion of mitochondrial biogenesis through activation of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) pathway, inhibiting mitochondrial degradation via decreased autophagy, and facilitating mitochondrial fragmentation involving increased levels of DRP1 and MFN2. The resulting reduced levels of dextran uptake, CD80, CD86 and chemokine receptor 7 (CCR7) suggested that PEG-Fe3 O4 nanoparticles impaired the functionally immature state of DCs. Autophagy inhibitor 3-methyladenine (3-MA) alleviated PEG-Fe3 O4 nanoparticle-induced mitochondrial instability and impairment of the functionally immature state of DCs due to unexpected enhancement of PGC1α/MFN2-mediated coordination of mitochondrial biogenesis and fusion.

GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca2+ signalling in a GABA-independent manner.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. Neurotransmitter-initiated signalling pathway is profoundly implicated in tumour initiation and progression. Here, we investigated whether dysregulated neurotransmitter receptors play a role during pancreatic tumourigenesis. METHODS: The Cancer Genome Atlas and Gene Expression Omnibus datasets were used to identify differentially expressed neurotransmitter receptors. The expression pattern of gamma-aminobutyric acid type A receptor pi subunit (GABRP) in human and mouse PDAC tissues and cells was studied by immunohistochemistry and western blot analysis. The in vivo implications of GABRP in PDAC were tested by subcutaneous xenograft model and lung metastasis model. Bioinformatics analysis, transwell experiment and orthotopic xenograft model were used to identify the in vitro and in vivo effects of GABRP on macrophages in PDAC. ELISA, co-immunoprecipitation, proximity ligation assay, electrophysiology, promoter luciferase activity and quantitative real-time PCR analyses were used to identify molecular mechanism. RESULTS: GABRP expression was remarkably increased in PDAC tissues and associated with poor prognosis, contributed to tumour growth and metastasis. GABRP was correlated with macrophage infiltration in PDAC and pharmacological deletion of macrophages largely abrogated the oncogenic functions of GABRP in PDAC. Mechanistically, GABRP interacted with KCNN4 to induce Ca2+ entry, which leads to activation of nuclear factor κB signalling and ultimately facilitates macrophage infiltration by inducing CXCL5 and CCL20 expression. CONCLUSIONS: Overexpressed GABRP exhibits an immunomodulatory role in PDAC in a neurotransmitter-independent manner. Targeting GABRP or its interaction partner KCNN4 may be an effective therapeutic strategy for PDAC.