High-Quality Data Enabling Universality of Band Gap Descriptor and Discovery of Photovoltaic Perovskites.

Extensive machine-learning-assisted research has been dedicated to predicting band gaps for perovskites, driven by their immense potential in photovoltaics. Yet, the effectiveness is often hampered by the lack of high-quality band gap data sets, particularly for perovskites involving d orbitals. In this work, we consistently calculate a large data set of band gaps with a high level of accuracy, which is rigorously validated by experimental and state-of-the-art GW band gaps. Leveraging this achievement, our machine-learning-derived descriptor exhibits exceptional universality and robustness, proving effectiveness not only for single and double, halide and oxide perovskites regardless of the underlying atomic structures but also for hybrid organic-inorganic perovskites. With this approach, we comprehensively explore up to 15,659 materials, unveiling 14 unreported lead-free perovskites with suitable band gaps for photovoltaics. Notably, MASnBr3, FA2SnGeBr6, MA2AuAuBr6, FA2AuAuBr6, FA2InBiCl6, FA2InBiBr6, and Ba2InBiO6 stand out with direct band gaps, small effective masses, low exciton binding energies, and high stabilities.

Association of self-reported arthritis with depression, anxiety, and comorbid depression/anxiety among the older Chinese adults: A cross-sectional study.

BACKGROUND: Arthritis is relatively common among middle-aged and older people and is a significant public health problem. However, research on the relationship between arthritis and mental health in older populations is currently limited. METHODS: Data were obtained from the Chinese Longitudinal Healthy Longevity Survey. The 10-item Center for Epidemiologic Studies Depression Scale and 7-item Generalized Anxiety Disorder Scale were used to evaluate depressive and anxiety symptoms. Arthritis status was self-reported. Linear and logistic regression analyses were conducted to assess the impact of arthritis on depression, anxiety, and comorbid depression/anxiety symptoms. RESULTS: A total of 11,104 participants aged ≥65 years (mean age, 83.1 ± 11.1 years) were included in the analysis. We detected positive associations of arthritis with depression symptoms (adjusted odds ratio [OR]: 1.57, 95 % confidence interval [CI] 1.33 to 1.86), anxiety symptoms (adjusted OR: 1.48, 95 % CI: 1.15 to 1.90), and comorbid depression/anxiety symptoms (adjusted OR: 1.88, 95 % CI: 1.41 to 2.5) in the older adult population. Participants with arthritis had higher anxiety (adjusted linear regression coefficient: 0.43, 95 % CI: 0.24 to 0.63) and depression (adjusted linear regression coefficient: 0.87, 95 % CI: 0.57 to 1.14) scores compared with those without arthritis. In addition, there were no significant interaction effects between arthritis and participant characteristics on depression symptoms, anxiety symptoms, or comorbid depression/anxiety symptoms. CONCLUSIONS: Arthritis was positively associated with depression symptoms, anxiety symptoms, and comorbid depression/anxiety symptoms among older adults. Further cohort studies are needed to validate these associations.

Chromogranin B (CHGB) is dimorphic and responsible for dominant anion channels delivered to cell surface via regulated secretion.

Regulated secretion is conserved in all eukaryotes. In vertebrates granin family proteins function in all key steps of regulated secretion. Phase separation and amyloid-based storage of proteins and small molecules in secretory granules require ion homeostasis to maintain their steady states, and thus need ion conductances in granule membranes. But granular ion channels are still elusive. Here we show that granule exocytosis in neuroendocrine cells delivers to cell surface dominant anion channels, to which chromogranin B (CHGB) is critical. Biochemical fractionation shows that native CHGB distributes nearly equally in soluble and membrane-bound forms, and both reconstitute highly selective anion channels in membrane. Confocal imaging resolves granular membrane components including proton pumps and CHGB in puncta on the cell surface after stimulated exocytosis. High pressure freezing immuno-EM reveals a major fraction of CHGB at granule membranes in rat pancreatic ß-cells. A cryo-EM structure of bCHGB dimer of a nominal 3.5 Å resolution delineates a central pore with end openings, physically sufficient for membrane-spanning and large single channel conductance. Together our data support that CHGB-containing (CHGB+) channels are characteristic of regulated secretion, and function in granule ion homeostasis near the plasma membrane or possibly in other intracellular processes.

Suggestive evidence of CYP4F2 gene polymorphisms with HAPE susceptibility in the Chinese Han population.

High altitude pulmonary edema (HAPE) is a common respiratory disease in the high altitude area, which is rapid and harmful. We firstly conducted a case-control study to assess the potential association of CYP4F2 gene polymorphisms with HAPE susceptibility in the Chinese Han population. The study recruited 238 patients with HAPE and 230 healthy controls in Northwest China. Genomic DNA was extracted from blood samples, and gene polymorphisms were detected using the Agena MassARRAY platform. Odds ratios (ORs), 95% confidence intervals (95% CIs), and P-value were used to evaluate the relationship between HAPE risk and CYP4F2 gene polymorphisms. Multi-factor dimension reduction (MDR) was used to assess the optimal interaction of CYP4F2 gene polymorphisms on HAPE risk. We found rs3093193 was shown to reduce the risk of HAPE (OR = 0.70, 95% CI = 0.52-0.93, P = 0.014), while rs12459936 was increased the susceptibility to HAPE (OR = 2.08, 95% CI = 1.33-3.26, P = 0.001). Age stratified analysis revealed that rs3093193 and rs12459936 were correlated with HAPE risk in people at age > 32 years old, and rs3093193 and rs3093110 were correlated with the HAPE risk in people at age ≤ 32 years old. Gender stratification analysis was found that rs3093193, rs12459936, and rs3093110 were all related to HAPE risk in males. A combination of rs12459936 and rs3093110 was the best multi-loci model with the highest testing accuracy. Our study is the first to provide the association between CYP4F2 gene polymorphisms and HAPE risk in the Chinese Han population.

Using Patient-Derived Xenograft (PDX) Models as a 'Black Box' to Identify More Applicable Patients for ADP-Ribose Polymerase Inhibitor (PARPi) Treatment in Ovarian Cancer: Searching for Novel Molecular and Clinical Biomarkers and Performing a Prospective Preclinical Trial.

(1) The accuracy of patient-derived xenografts (PDXs) in predicting ADP-ribose polymerase inhibitor (PARPi) efficacy in ovarian cancer was tested, novel biomarkers were investigated, and whether PARPis could replace platinum-based chemotherapy as a first-line therapy was explored. (2) PDXs were reconstructed for 40 patients with ovarian cancer, and niraparib, olaparib and paclitaxel, and carboplatin (TC) sensitivity tests were conducted. Whole exon sequencing and homologous recombination deficiency (HRD) scores were performed, and patient clinical information was collected. The molecular biomarkers were identified by reverse-transcription quantitative PCR and immunoblotting. (3) Niraparib and olaparib sensitivity were tested in 26 patients and showed high consistency. Approximately half of BRCA wild-type, HRD-negative, and platinum-resistant patients may benefit from PARPis. AKT1 enrichment indicated PARPi resistance; high KRAS expression indicated PARPi sensitivity. CA125 below 10 U/mL during chemotherapy has a sensitivity and specificity similar to platinum sensitivity in predicting PARPi efficacy. Niraparib and TC sensitivity tests were performed on 23 patients, and TC showed a better response in this preclinical trial. (4) PDX can indicate individualized PARPi efficacy. Decreased CA125 levels and KRAS and ATK1 expression levels may be novel biomarkers. The preclinical evidence does not support the implementation of PARPis as the first-line treatment in an unselected population.

UAV imaging and deep learning based method for predicting residual film in cotton field plough layer.

In this paper, a method for predicting residual film content in the cotton field plough layer based on UAV imaging and deep learning was proposed to solve the issues of high labour intensity, low efficiency, and high cost of traditional methods for residual film content monitoring. Images of residual film on soil surface in the cotton field were collected by UAV, and residual film content in the plough layer was obtained by manual sampling. Based on the three deep learning frameworks of LinkNet, FCN, and DeepLabv3, a model for segmenting residual film from the cotton field image was built. After comparing the segmentation results, DeepLabv3 was determined to be the best model for segmenting residual film, and then the area of residual film was obtained. In addition, a linear regression prediction model between the residual film coverage area on the cotton field surface and the residual film content in the plough layer was built. The results showed that the correlation coefficient (R2), root mean square error, and average relative error of the prediction of residual film content in the plough layer were 0.83, 0.48, and 11.06%, respectively. It indicates that a quick and accurate prediction of residual film content in the cotton field plough layer can be realized based on UAV imaging and deep learning. This study provides certain technical support for monitoring and evaluating residual film pollution in the cotton field plough layer.

Evaluation of residual plastic film pollution in pre-sowing cotton field using UAV imaging and semantic segmentation.

To accurately evaluate residual plastic film pollution in pre-sowing cotton fields, a method based on modified U-Net model was proposed in this research. Images of pre-sowing cotton fields were collected using UAV imaging from different heights under different weather conditions. Residual films were manually labelled, and the degree of residual film pollution was defined based on the residual film coverage rate. The modified U-Net model for evaluating residual film pollution was built by simplifying the U-Net model framework and introducing the inception module, and the evaluation results were compared to those of the U-Net, SegNet, and FCN models. The segmentation results showed that the modified U-Net model had the best performance, with a mean intersection over union (MIOU) of 87.53%. The segmentation results on images of cloudy days were better than those on images of sunny days, with accuracy gradually decreasing with increasing image-acquiring height. The evaluation results of residual film pollution showed that the modified U-Net model outperformed the other models. The coefficient of determination(R2), root mean square error (RMSE), mean relative error (MRE) and average evaluation time per image of the modified U-Net model on the CPU were 0.9849, 0.0563, 5.33% and 4.85 s, respectively. The results indicate that UAV imaging combined with the modified U-Net model can accurately evaluate residual film pollution. This study provides technical support for the rapid and accurate evaluation of residual plastic film pollution in pre-sowing cotton fields.

New insights into ESIPT mechanism of three sunscreen compounds in solution: A combined experimental and theoretical study.

In this present work, we have successfully designed and investigated three flavonoid sunscreen compounds. Based on steady-state spectroscopy and time-dependent density functional theory (TDDFT), the mechanism of excited state intramolecular proton transfer (ESIPT) of sunscreen compounds was studied. The calculated UV-vis absorption spectra and fluorescence emission spectra are in good agreement with the experimental results in methanol solution. The potential energy curve demonstrates that the ESIPT process can easily occur in the three sunscreen compounds without energy barrier. Therefore, the absorbed excitation energy can get back to the ground state through a non-radiative relaxation process. Light stability tests ensure that the three flavonoids have the potential as sunscreens. This work provides not only an application of the ESIPT process in sunscreen mechanisms, but also a theory basis for the development of novel sunscreen molecules.

Temperature-Dependent Electronic Ground-State Charge Transfer in van der Waals Heterostructures.

Electronic charge rearrangement between components of a heterostructure is the fundamental principle to reach the electronic ground state. It is acknowledged that the density of state distribution of the components governs the amount of charge transfer, but a notable dependence on temperature is not yet considered, particularly for weakly interacting systems. Here, it is experimentally observed that the amount of ground-state charge transfer in a van der Waals heterostructure formed by monolayer MoS2 sandwiched between graphite and a molecular electron acceptor layer increases by a factor of 3 when going from 7 K to room temperature. State-of-the-art electronic structure calculations of the full heterostructure that accounts for nuclear thermal fluctuations reveal intracomponent electron-phonon coupling and intercomponent electronic coupling as the key factors determining the amount of charge transfer. This conclusion is rationalized by a model applicable to multicomponent van der Waals heterostructures.

High-mobility group box protein-1 induces acute pancreatitis through activation of neutrophil extracellular trap and subsequent production of IL-1ß.

PURPOSE: The aim of this study is to evaluate acute pancreatitis (AP)-associated NET activation mediated by a novel inflammatory mediator (high-mobility group box protein-1 [HMGB1]) and proinflammatory cytokine responses. METHODS: In this study, primary neutrophils, monocytes, and monocytic cell line Thp-1-derived macrophages were isolated and treated with HMGB1, lipopolysaccharide (LPS), adenosine triphosphate (ATP), and ATP + ATP inhibitor. The effects of HMGB1, ATP, and deoxyribonuclease (DNAse) were then examined for their in vivo effects using a newly established AP mouse model. RESULTS: The mRNA and protein levels of inflammasome and interleukin IL-1ß in cells, blood, and pancreatic tissues were examined. Within-cell nuclear DNA signal, cell-free DNA concentration, and pancreatic tissue damage were investigated. Our study showed that HMGB1 triggers NET formation in neutrophils and promotes the activation of inflammasome complexes (the NLR family, pyrin domain containing 3, and NLRP3; ASC; and caspase-1); therefore, the production of IL-1ß is induced in human monocytes/macrophages. HMGB1 and NET cooperatively stimulate IL-1ß processing in macrophages. Furthermore, the AP mouse model confirmed these HMGB1-mediated molecular mechanisms in vivo and indicated that HMGB1 is required for NET activation. CONCLUSIONS: We found that NET inhibition reverses HMGB1-stimulated inflammasome activation and IL-1ß production. HMGB1 thus leads to pancreatic injury through the activation of NET and subsequently induces IL-1ß processing from neutrophils to pancreatic tissues. These findings demonstrate that HMGB1 and NET are new therapeutic targets for inflammation suppression in severe AP.

Excited state electronic structures and photochemistry of different oxidation states of 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS).

The molecular structures of 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), were calculated by using time-dependent density functional theory (TDDFT) model with M062X method with 6-311G (d, p) basis set. In this work, the ABTS were theoretically investigated from the geometric structure, the energy levels of the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO), the energy level gap ΔEHOMO-LUMO of the molecular ground state, excited stated properties and the electronic absorption spectra of different oxidation states. We studied the energy levels of LUMO and HOMO of ABTS in different oxidation states. Frontier molecular orbital analysis can provide insight into the nature of excited states. ABTS was synthesized from N-ethylamine by total synthesis. Then, we measured the UV-Vis spectra of ABTS before and after being oxidized by K2S2O8. The calculated electronic structures and photochemical properties of different oxidation state of ABTS were in accordance with the experimental result. This work demonstrates the relationship between the electronic structures and photochemistry of different oxidation states ABTS hence paves the way for the rationally synthesis and deepen understanding of the photophysical properties of ABTS materials.

Mechanisms of proton inhibition and sensitization of the cation channel TRPV3.

TRPV3 is a temperature-sensitive, nonselective cation channel expressed prominently in skin keratinocytes. TRPV3 plays important roles in hair morphogenesis and maintenance of epidermal barrier function. Gain-of-function mutations of TRPV3 have been found in both humans and rodents and are associated with hair loss, pruritus, and dermatitis. Here, we study the mechanisms of acid regulation of TRPV3 by using site-directed mutagenesis, fluorescent intracellular calcium measurement, and whole-cell patch-clamp recording techniques. We show that, whereas extracellular acid inhibits agonist-induced TRPV3 activation through an aspartate residue (D641) in the selectivity filter, intracellular protons sensitize the channel through cytoplasmic C-terminal glutamate and aspartate residues (E682, E689, and D727). Neutralization of the three C-terminal residues presensitizes the channel to agonist stimulation. Molecular dynamic simulations revealed that charge neutralization of the three C-terminal residues stabilized the sensitized channel conformation and enhanced the probability of α-helix formation in the linker between the S6 transmembrane segment and TRP domain. We conclude that acid inhibits TRPV3 function from the extracellular side but facilitates it from the intracellular side. These novel mechanisms of TRPV3 proton sensing can offer new insights into the role of TRPV3 in the regulation of epidermal barrier permeability and skin disorders under conditions of tissue acidosis.

Structure-Based Modification of an Anti-neuraminidase Human Antibody Restores Protection Efficacy against the Drifted Influenza Virus.

Here, we investigate a monoclonal antibody, Z2B3, isolated from an H7N9-infected patient, that exhibited cross-reactivity to both N9 (group 2) and a broad range of seasonal and avian N1 (group 1) proteins but lost activity to the N1 with the substitution K432E. This substitution exists in 99.25% of seasonal influenza strains after 2013. The NA-Z2B3 complex structures indicated that Z2B3 binds within the conserved active site of the neuraminidase (NA) protein. A salt bridge between D102 in Z2B3 and K432 in NA plays an important role in binding. Structure-based modification of Z2B3 with D102R in heavy chain reversed the salt bridge and restored the binding and inhibition of N1 with E432. Furthermore, Z2B3-D102R can protect mice from A/Serbia/NS-601/2014 H1N1 virus (NA contains E432) infection while the wild-type Z2B3 antibody shows no protection. This study demonstrates that a broadly reactive and protective antibody to NA can be in principle edited to restore binding and inhibition to recently drifted N1 NA and regain protection against the variant influenza strain.IMPORTANCE The immune system produces antibodies to protect the human body from harmful invaders. The monoclonal antibody (MAb) is one kind of effective antivirals. In this study, we isolated an antibody (Z2B3) from an H7N9 influenza virus-infected child. It shows cross-reactivity to both group 1 (N1) and group 2 (N9) neuraminidases (NAs) but is sensitive to N1 NA with a K432E substitution. Structural analysis of the NA-antibody fragment antigen-binding (Fab) complex provides a clue for antibody modification, and the modified antibody restored binding and inhibition to recently drifted N1 NA and regained protection against the variant influenza strain. This finding suggests that antibodies to NA may be a useful therapy and can be in principle edited to defeat drifted influenza virus.

A simulation training course for family medicine residents in China managing COVID-19.

BACKGROUND AND OBJECTIVES: As a result of the pandemic, family physicians face the additional challenge of navigating COVID-19. The aim of this study was to provide simulated training for best-practice management of COVID-19 presentations for residency program trainees in Shanghai, China. METHOD: A simulated suspected COVID-19 case was designed on the basis of a real patient. The simulation included: pre­ and post-simulation surveys, a PowerPoint presentation, simulation practice, debriefing and reflection. Improvement in survey outcomes was assessed using a paired t-test. RESULTS: A total of 25 trainees participated in the simulation, consisting of first-, second- and third-year family medicine residents. Significant improvement was observed in their knowledge of COVID-19, and sub-analysis showed that all three grades of residents improved their knowledge significantly. Ninety-six per cent of participants believed the simulation was very helpful. DISCUSSION: The simulation scenario improves crisis management skills for family physicians managing the high risk of transmission of respiratory infectious diseases. Higher-order learning outcomes will be explored in future training programs.

Ultrafast Nonadiabatic Photoisomerization Dynamics Mechanism for the UV Photoprotection of Stilbenoids in Grape Skin.

Natural UV photoprotection plays a vital role in physiological protection. It has been reported that UVC radiation can make resveratrol (RSV) and piceatannol (PIC) accumulate in grape skin. In this work, we demonstrated that RSV and PIC could significantly absorb UVA and UVB, and confirmed their satisfactory photostability. Furthermore, we clarified the UV photoprotection mechanism of typical stilbenoids of RSV and PIC for the first time by using combined femtosecond transient absorption (FTA) spectroscopy and time-dependent density functional theory (TD-DFT) calculations. RSV and PIC can be photoexcited to the excited state after UVA and UVB absorption. Subsequently, the photoisomerized RSV and PIC quickly relax to the ground state via nonadiabatic transition from the S1 state at a conical intersection (CI) position between potential energy surfaces (PESs) of S1 and S0 states. This ultrafast trans-cis photoisomerization will take place within a few tens of picoseconds. As a result, the UV energy absorbed by RSV and PIC could be dissipated by an ultrafast nonadiabatic photoisomerization process.

Avian-to-Human Receptor-Binding Adaptation of Avian H7N9 Influenza Virus Hemagglutinin.

Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,600 human infections, posing a threat to public health. An emerging concern is whether H7N9 AIVs will cause pandemics among humans. Molecular analysis of hemagglutinin (HA), which is a critical determinant of interspecies transmission, shows that the current H7N9 AIVs are still dual-receptor tropic, indicating limited human-to-human transmission potency. Mutagenesis and structural studies reveal that a G186V substitution is sufficient for H7N9 AIVs to acquire human receptor-binding capacity, and a Q226L substitution would favor binding to both avian and human receptors only when paired with A138/V186/P221 hydrophobic residues. These data suggest a different evolutionary route of H7N9 viruses compared to other AIV-subtype HAs.

Systematic Review and Meta-Analysis of 12 Randomized Controlled Trials Evaluating the Efficacy of Invasive Radiofrequency Treatment for Knee Pain and Function.

Radiofrequency (RF) treatment is an invasive and promising procedure in the treatment of osteoarthritis (OA). A meta-analysis based on 12 RCT studies was to investigate whether invasive RF treatment is more effective in relieving knee pain and improving knee function. Relevant studies were searched on database of Pubmed, Embase, EBSCO, Cochrane library, Wanfang digital database, VIP database, and CNKI up to January 2018. A total of 841 participants from 12 publications were included. The weighted mean difference (WMD) and the corresponding 95% CIs were used to evaluate the difference in pain scores and OKS/WOMAC scores between RF treatment and control groups. The statistical analysis was performed by Stata 12.0. The pain scores (VAS) in the RF group were lower than those in the conservative treatment group after 1 week (WMD -1.77, 95% CI -2.93 to -0.61, P<0.01), 1 month (WMD -1.40, 95% CI -1.98 to -0.82, P<0.01), and 3 months (WMD -1.32, 95% CI -2.27 to -0.37, P<0.01) of treatment, while there was no significant improvement in knee function. In subgroup analyses by site of radiofrequency, RF mode showed some discrepancies in the WMD of VAS between the treatment and control groups. In addition, subgroup analysis and meta-regression showed that the efficacy of RF treatment for reducing pain is reversely related to female ratio, and we did not find any surgery-related adverse reactions. RF treatment significantly reduces the knee pain, but rarely improves the knee joint function. Radiofrequency ablation has better efficacy than pulsed radiofrequency ablation in reducing pain. Furthermore, subgroup analysis and meta-regression suggested that women are more sensitive to RF treatment than men.

Molecular Basis of Arthritogenic Alphavirus Receptor MXRA8 Binding to Chikungunya Virus Envelope Protein.

Arthritogenic alphaviruses, such as Chikungunya virus (CHIKV), cause severe and debilitating rheumatic diseases worldwide, resulting in severe morbidity and economic costs. Recently, MXRA8 was reported as an entry receptor. Here, we present the crystal structures of the mouse MXRA8, human MXRA8 in complex with the CHIKV E protein, and the cryo-electron microscopy structure of human MXRA8 and CHIKV virus-like particle. MXRA8 has two Ig-like domains with unique structural topologies. This receptor binds in the "canyon" between two protomers of the E spike on the surface of the virion. The atomic details at the interface between the two binding entities reveal that both the two domains and the hinge region of MXRA8 are involved in interaction with CHIKV E1-E2 residues from two protomers. Notably, the stalk region of MXRA8 is critical for CHIKV virus entry. This finding provides important information regarding the development of therapeutic countermeasures against those arthritogenic alphaviruses.

Anti-Multipath Performance Improvement of an M-ary Position Phase Shift Keying Modulation System.

Low-Power Wide-Area Network (LPWAN) is the technology that the Internet-of-Things (IoT) uses in long-distance, wide-coverage scenarios. As one of the ultra-narrowband (UNB) modulation techniques, M-ary position phase shift keying (MPPSK) modulation can provide high coverage and high reliability for LPWAN. This paper proposes a multipath separation method based on MPPSK modulation, which aims to eliminate the influence of multipath on the main path without increasing the spectrum overhead and system complexity. Specifically, the modulation parameter of the system is adjusted according to the delay value, so that the phase jump of the multipath signal falls outside the phase jump of the main path symbol to achieve separation of the multipath from the main path. Moreover, a normalized symbol joint decision method is proposed in order to reduce the introduced noise while using multipath information for decisions. The simulation results indicate that the multipath separation conditions given in this paper can meet the requirements of multipath separation of MPPSK signals. Compared with the existing mainstream decision scheme, the normalized symbol joint decision improves the demodulation performance of the system.

The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.

Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy. Identification of the "hotspots" on PD-1 for mAbs will help to develop next-generation oral deliverable agents with long-lasting efficacy. Here, we identified two PD-1-targeting mAbs, GY-5 and GY-14, with PD-1/PD-L1-blocking efficacy. Complex structural information revealed that both mAbs mainly bind to the FG loop of PD-1, which also contributes multiple interactions with PD-L1. The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules. Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites. However, the binding of GY-5 and GY-14 to PD-1 was not affected by glycosylation. These findings broaden our understanding of the mechanism of anti-PD-1 mAbs and provide insight into the development of agents targeting PD-1.