Laparoscopic Tracer Technique for Liver Lymphatic Drainage by Injecting Indocyanine Green into the Glisson Pedicle.

BACKGROUND: Currently, an effective tracer technique for lymphatic drainage during laparoscopic surgery has not been established. This study aimed to elucidate a new fluorescence, imaging technique targeting the hepatic lymphatic drainage area, using indocyanine green (ICG). METHODS: A patient diagnosed with intrahepatic cholangiocarcinoma (ICC) located in segment 8 of the liver was injected with ICG into the connective tissue of the Glisson pedicle supplied by the lesion's liver segment, avoiding the bile duct, portal vein, and hepatic artery. This was performed under the guidance of laparoscopic ultrasonographic localization to trace the lymph nodes. RESULTS: The lymphatic drainage area traced intraoperatively by ICG was consistent with the definition of the right regional lymph nodes for ICC. The lymph nodes were dissected, followed by addition of a fluorescence tracer. CONCLUSIONS: Mastering intraoperative ultrasonic puncture technology can enable effective and accurate tracing of the lymph nodes of the liver segment where the lesion is located. However, the technical standards for this methodology need to be established through further studies.

Appendicoscopy using single-operator cholangioscope in the management of acute obstructive appendicitis: a novel alternative (with video).

BACKGROUND AND AIMS: The aim of this study was to investigate the safety and efficacy of appendicoscopy using a single-operator cholangioscope (SOC) for the management of acute obstructive appendicitis. METHODS: This study describes 110 cases of acute obstructive appendicitis managed with the use of appendicoscopy between January 2021 and June 2023. The success rate (technical + clinical), procedure time, time to abdominal pain relief according to a visual analog scale score, postoperative length of hospital stay, and adverse event rates were recorded and analyzed. RESULTS: The technical success rate of appendicoscopy was 96.4%, and the clinical success rate was 91.8%. The mean ± standard deviation procedure time was 20.9 ± 10 minutes. The abdominal pain score at 6 hours after the procedure was ≤3 (visual analog scale method) in 99.1% of patients. The average length of postoperative hospital stay was 3.5 ± 1.5 days. No adverse events occurred. CONCLUSIONS: Appendicoscopy seems to be a feasible and effective alternative therapy for the accurate diagnosis and treatment of acute obstructive appendicitis.

Thickness-Dependent Interface Polarity in Infinite-Layer Nickelate Superlattices.

The interface polarity plays a vital role in the physical properties of oxide heterointerfaces because it can cause specific modifications of the electronic and atomic structure. Reconstruction due to the strong polarity of the NdNiO2/SrTiO3 interface in recently discovered superconducting nickelate films may play an important role, as no superconductivity has been observed in the bulk. By employing four-dimensional scanning transmission electron microscopy and electron energy-loss spectroscopy, we studied effects of oxygen distribution, polyhedral distortion, elemental intermixing, and dimensionality in NdNiO2/SrTiO3 superlattices grown on SrTiO3 (001) substrates. Oxygen distribution maps show a gradual variation of the oxygen content in the nickelate layer. Remarkably, we demonstrate thickness-dependent interface reconstruction due to a polar discontinuity. An average cation displacement of ∼0.025 nm at interfaces in 8NdNiO2/4SrTiO3 superlattices is twice larger than that in 4NdNiO2/2SrTiO3 superlattices. Our results provide insights into the understanding of reconstructions at NdNiO2/SrTiO3 polar interfaces.

Laparoscopic Anatomical Liver Resection of Segment VIII by Using ICG Fluorescence Positive Staining Under the Guidance of Laparoscopic Ultrasonography.

BACKGROUND: Anatomical segmentectomy is a surgical procedure that completely removes a territory (or territories) of the third-order portal venous branches of a Couinaud segment (Wakabayashi et al. in J Hepatobil Pancreat Sci 29(1):82-98, 2022. https://doi.org/10.1002/jhbp.899 ). Laparoscopic segmentectomy of S8 is considered technically challenging because of the Precise dissection of the Glissonean pedicle of S8, and exposure of the middle and right hepatic veins are required (Ome et al. in J Am Coll Surg 230(3):e13-e20, 2020; Wakabayashi et al. in Ann Surg 261(4):619-29, 2015. https://doi.org/10.1097/sla.0000000000001184 ; Monden et al. in J Hepatobil Pancreat Sci 29(1):66-81, 2022. https://doi.org/10.1002/jhbp.898 ). This report describes a new approach, which can reduce unwanted damage to normal tissues and complications. METHODS: A 53-year-old man who has suffered from hepatitis B for 10 years was admitted for the treatment of two nodular tumors located in segment VIII. The surgical procedure began with the percutaneous injection of 5 mL, 0.025 mg/mL of ICG into the S8 portal branch by using an 18G PTCD needle under the guidance of laparoscopic ultrasound (Xu et al. in Surg Endosc 34(10):4683-4691, 2020. https://doi.org/10.1007/s00464-020-07691-5 ; Wang et al. in Ann Surg 274(1):97-106, 2021. https://doi.org/10.1097/sla.0000000000004718 ; Aoki et al. in J Am Coll Surg 230(3):e7-e12, 2020. https://doi.org/10.1016/j.jamcollsurg.2019.11.004 ), followed by liver transection on the cranial side of the liver, which used the ICG fluorescence images for exposing the roots of the middle and right hepatic veins and dissecting and ligating S8 portal pedicle. The excision specimen was sent for histopathological diagnosis. RESULTS: It took 200 min for the operation and 60 min for the total Pringle maneuver. The estimate of blood loss was 110 mL. The final histopathologic results of the two nodules were hepatocellular carcinoma (HCC). The patient was discharged on postoperative Day 6 with no complications. CONCLUSIONS: Laparoscopic anatomical liver resection of S8 has been demonstrated to be feasible. Under the guidance of laparoscopic ultrasonography, ICG positive staining was proven to be optimal for Anatomical segmentectomy.

A novel two-dimensional NiCl2O8 lattice with negative Poisson's ratio and magnetic modulation.

Two-dimensional (2D) materials with simultaneous magnetic semiconducting properties and a negative Poisson's ratio are crucial for fabricating multifunctional electronic devices. However, progress in this area has been generally constrained. Based on first-principles calculations, we engineered a 2D Ni-based oxyhalide with a honeycomb lattice structure. It was observed that the NiCl2O8 monolayer exhibits both high- and low-buckling states in its geometry, along with intrinsic magnetic semiconductor properties in its electronic structure. Importantly, we demonstrated that the magnetic ordering of the NiCl2O8 lattice is susceptible to applied strain, which resulted in a phase transition from paramagnetic to ferromagnetic under biaxial strain. The Curie temperature was also evaluated using Monte Carlo simulations within the Ising model. Additionally, our research uncovered that the 2D NiCl2O8 lattice chain displays a negative Poisson's ratio (NPR) along the z-direction. The triangular hinge structure in its centrosymmetric configuration was identified as the origin of this unique phenomenon. The coexistence of NPR and magnetic phase transition properties in the NiCl2O8 lattice makes it quite promising for applications in nanoelectronic and spintronic devices.

Permeability enhancement of Kv1.2 potassium channel by a terahertz electromagnetic field.

As biomolecules vibrate and rotate in the terahertz band, the biological effects of terahertz electromagnetic fields have drawn considerable attention from the physiological and medical communities. Ion channels are the basis of biological electrical signals, so studying the effect of terahertz electromagnetic fields on ion channels is significant. In this paper, the effect of a terahertz electromagnetic field with three different frequencies, 6, 15, and 25 THz, on the Kv1.2 potassium ion channel was investigated by molecular dynamics simulations. The results show that an electromagnetic field with a 15 THz frequency can significantly enhance the permeability of the Kv1.2 potassium ion channel, which is 1.7 times higher than without an applied electric field. By analyzing the behavior of water molecules, it is found that the electromagnetic field with the 15 THz frequency shortens the duration of frozen and relaxation processes when potassium ions pass through the channel, increases the proportion of the direct knock-on mode, and, thus, enhances the permeability of the Kv1.2 potassium ion channel.

Metabolic disorders induced by PNPLA3 and TM6SF2 gene variants affect chronic kidney disease in patients infected with non-genotype 3 hepatitis C virus.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infections differ in their risk for metabolic disorders and chronic kidney disease (CKD). The aim of this study was to investigate the effect of metabolic disorders induced by genetic factors on CKD in HCV-infected patients. METHODS: Patients with chronic non-genotype 3 HCV infection with or without CKD were examined. PNPLA3 and TM6SF2 variants were determined using high-throughput sequencing. The relationships of variants and different combinations with metabolic disorders were analyzed in CKD patients. Univariate and multivariate analyses were used to identify factors associated with CKD. RESULTS: There were 1022 patients with chronic HCV infection, 226 with CKD and 796 without CKD. The CKD group had more severe metabolic disorders, and also had higher prevalences of liver steatosis, the PNPLA3 rs738409 non-CC genotype, and the TM6SF2 rs58542926 CC genotype (all P < 0.05). Relative to patients with the PNPLA3 rs738409 CC genotype, patients with the non-CC genotype had a significantly decreased eGFR and a greater prevalence of advanced CKD (CKD G4-5). Patients with the TM6SF2 rs58542926 CC genotype had a lower eGFR and a higher prevalence of CKD G4-5 than those with the non-CC genotype. Multivariable analysis indicated that multiple metabolic abnormalities, including liver steatosis and the PNPLA3 rs738409 C > G variant, increased the risk of CKD, but the TM6SF2 rs58542926 C > T variant decreased the risk of CKD. CONCLUSION: Specific PNPLA3 rs738409 and TM6SF2 rs58542926 variants are independent risk factors for CKD in patients with chronic HCV infections and are associated with the severity of renal injury.

Effect of THz Waves of Different Orientations on K+ Permeation Efficiency in the KcsA Channel.

Potassium (K) channels show the highest variability and most frequent alterations in expression in many tumor types, and modulation of K+ channels may represent a new window for cancer therapy. In previous work, we found that a terahertz (THz) field incident along the z-axis with a frequency of 51.87 THz increased the ion flux through K+ channels. In practice, it is difficult to ensure that the incident electromagnetic (EM) wave is strictly parallel to the direction of channel ion flow. In this paper, we found by changing the direction of the applied electric field that the EM wave of a specific frequency has the largest ion flux when the incident direction is along the ion flow, and the smallest ion flux when the incident direction is perpendicular to the ion flow, and that overall the EM wave of this frequency enhances the ion flow of the K+ channel. Changes in the direction of the applied field at a specific frequency affect the stability of the φ dihedral angle of the GLY77 residue and alter the ion permeation mechanism in the selectivity filter (SF) region, thus affecting the ion flux. Therefore, this frequency can be used to modulate K+ fluxes by THz waves to cause rapid apoptosis in potassium-overloaded tumor cells. This approach consequently represents an important tool for the treatment of cancer and is expected to be applied in practical therapy.

Effect of Terahertz Electromagnetic Field on the Permeability of Potassium Channel Kv1.2.

In this paper, the influence of external terahertz electromagnetic fields with different frequencies of 4 THz, 10 THz, 15 THz, and 20 THz on the permeability of the Kv1.2 voltage-gated potassium ion channel on the nerve cell membrane was studied using the combined model of the "Constant Electric Field-Ion Imbalance" method by molecular dynamics. We found that although the applied terahertz electric field does not produce strong resonance with the -C=O groups of the conservative sequence T-V-G-Y-G amino acid residue of the selective filter (SF) of the channel, it would affect the stability of the electrostatic bond between potassium ions and the carbonyl group of T-V-G-Y-G of SF, and it would affect the stability of the hydrogen bond between water molecules and oxygen atoms of the hydroxyl group of the 374THR side chain at the SF entrance, changing the potential and occupied states of ions in the SF and the occurrence probability of the permeation mode of ions and resulting in the change in the permeability of the channel. Compared with no external electric field, when the external electric field with 15 THz frequency is applied, the lifetime of the hydrogen bond is reduced by 29%, the probability of the "soft knock on" mode is decreased by 46.9%, and the ion flux of the channel is activated by 67.7%. Our research results support the view that compared to "direct knock-on", "soft knock-on" is a slower permeation mode.

Exfoliated 2D Layered and Nonlayered Metal Phosphorous Trichalcogenides Nanosheets as Promising Electrocatalysts for CO2 Reduction.

Two-dimensional (2D) materials catalysts provide an atomic-scale view on a fascinating arena for understanding the mechanism of electrocatalytic carbon dioxide reduction (CO2 ECR). Here, we successfully exfoliated both layered and nonlayered ultra-thin metal phosphorous trichalcogenides (MPCh3 ) nanosheets via wet grinding exfoliation (WGE), and systematically investigated the mechanism of MPCh3 as catalysts for CO2 ECR. Unlike the layered CoPS3 and NiPS3 nanosheets, the active Sn atoms tend to be exposed on the surfaces of nonlayered SnPS3 nanosheets. Correspondingly, the nonlayered SnPS3 nanosheets exhibit clearly improved catalytic activity, showing formic acid selectivity up to 31.6 % with -7.51 mA cm-2 at -0.65 V vs. RHE. The enhanced catalytic performance can be attributed to the formation of HCOO* via the first proton-electron pair addition on the SnPS3 surface. These results provide a new avenue to understand the novel CO2 ECR mechanism of Sn-based and MPCh3 -based catalysts.

Effect of an artificial intelligence-based quality improvement system on efficacy of a computer-aided detection system in colonoscopy: a four-group parallel study.

BACKGROUND: Tandem colonoscopy studies have found that about one in five adenomas are missed at colonoscopy. It remains debatable whether the combination of a computer-aided polyp detection (CADe) system with a computer-aided quality improvement (CAQ) system for real-time monitoring of withdrawal speed results in additional benefits in adenoma detection or if the synergetic effect may be harmed due to excessive visual burden resulting from information overload. This study aimed to evaluate the interaction effect on improving the adenoma detection rate (ADR). METHODS: This single-center, randomized, four-group, parallel, controlled study was performed at Renmin Hospital of Wuhan University. Between 1 July and 15 October 2020, 1076 patients were randomly allocated into four treatment groups: control 271, CADe 268, CAQ 269, and CADe plus CAQ (COMBO) 268. The primary outcome was ADR. RESULTS: The ADR in the control, CADe, CAQ, and COMBO groups was 14.76 % (95 % confidence interval [CI] 10.54 to 18.98), 21.27 % (95 %CI 16.37 to 26.17), 24.54 % (95 %CI 19.39 to 29.68), and 30.60 % (95 %CI 25.08 to 36.11), respectively. The ADR was higher in the COMBO group compared with the CADe group (21.27 % vs. 30.6 %, P = 0.024, odds ratio [OR] 1.284, 95 %CI 1.033 to 1.596) but not compared with the CAQ group (24.54 % vs. 30.6 %, P = 0.213, OR 1.309, 95 %CI 0.857 to 2.000, respectively). CONCLUSIONS: CAQ significantly improved the efficacy of CADe in a four-group, parallel, controlled study. No significant difference in the ADR or polyp detection rate was found between CAQ and COMBO.

Regulation of Ion Permeation of the KcsA Channel by Applied Midinfrared Field.

Ion transport molecules are involved in many physiological and pathological processes and are considered potential targets for cancer treatment. In the large family of ion transport molecules, potassium (K) ion channels, as surface-expressed proteins, show the highest variability and most frequent expression changes in many tumor types. The key to exploring the permeation of K+ through potassium channels lies in the conserved sequence TVGYG, which is common in the selectivity filter (SF) region of all potassium channels. We found that the K+ flux significantly increased with the help of a specific frequency terahertz electromagnetic wave (51.87 THz) in the KcsA channel using a molecular dynamics combined model through the combined simulation of the constant electric field method and ion imbalance method. This frequency has the strongest absorption peak in the infrared spectrum of -C=O groups in the SF region. With the applied electric field of 51.87 THz, the Y78 residue at the S1 site of the SF has a smaller vibration amplitude and a more stable structure, which enables the K+ to bind closely with the carbonyl oxygen atoms in the SF and realize ion conduction in a more efficient direct Coulomb knock-on.

Assembling Metal Organic Layer Composites for High-Performance Electrocatalytic CO2 Reduction to Formate.

2D metal-organic-framework (MOF) based composites have emerged as promising candidates for electrocatalysis due to their high structural flexibility and fully exposed active sites. Herein, a freestanding metal-organic layer (MOL) with a 2D kgd (kagome dual) lattice was constructed with abundant surface oxygenate groups serving as anchoring sites to immobilize diverse guests. Taking Bi as an example, tetragonal Bi2 O3 nanowires can be uniformly grown on MOLs after solvothermal treatment, the structural evolution of which was followed by ex situ electron microscopy. The as-prepared Bi2 O3 /MOL exhibits excellent CO2 electroreduction activity towards formate reaching a specific current of 2.3 A mgBi -1 and Faradaic efficiencies of over 85 % with a wide potential range from -0.87 to -1.17 V, far surpassing Bi2 O3 /UiO (a 3D Zr6 -oxo based MOF) and Bi2 O3 /AB (Acetylene Black). Such a post-synthetic modification strategy can be flexibly extended to develop versatile MOL composites, highlighting the superiority of optimizing MOL-based composites for electrocatalysis.

Consensus Guidelines for the Use of Fluorescence Imaging in Hepatobiliary Surgery.

OBJECTIVE: To establish consensus recommendations for the use of fluorescence imaging with indocyanine green (ICG) in hepatobiliary surgery. BACKGROUND: ICG fluorescence imaging has gained popularity in hepatobiliary surgery in recent years. However, there is varied evidence on the use, dosage, and timing of administration of ICG in clinical practice. To standardize the use of this imaging modality in hepatobiliary surgery, a panel of pioneering experts from the Asia-Pacific region sought to establish a set of consensus recommendations by consolidating the available evidence and clinical experiences. METHODS: A total of 13 surgeons experienced in hepatobiliary surgery and/or minimally invasive surgery formed an expert consensus panel in Shanghai, China in October 2018. By the modified Delphi method, they presented the relevant evidence, discussed clinical experiences, and derived consensus statements on the use of ICG in hepatobiliary surgery. Each statement was discussed and modified until a unanimous consensus was achieved. RESULTS: A total of 7 recommendations for the clinical applications of ICG in hepatobiliary surgery were formulated. CONCLUSIONS: The Shanghai consensus recommendations offer practical tips and techniques to augment the safety and technical feasibility of ICG fluorescence-guided hepatobiliary surgery, including laparoscopic cholecystectomy, liver segmentectomy, and liver transplantation.

Facile Preparation of MoS2 Nanocomposites for Efficient Potassium-Ion Batteries by Grinding-Promoted Intercalation Exfoliation.

Efficient exfoliations of bulk molybdenum disulfide (MoS2 ) into few-layered nanosheets in pure phase are highly attractive because of the promising applications of the resulted 2D materials in diversified optoelectronic devices. Here, a new exfoliation method is presented to prepare semiconductive 2D hexagonal phase (2H phase) MoS2 -cellulose nanocrystal (CNC) nanocomposites using grinding-promoted intercalation exfoliation (GPIE). This method with facile grinding of the bulk MoS2 and CNC powder followed by conventional liquid-phase exfoliation in water can not only efficiently exfoliate 2H-MoS2 nanosheets, but also produce the 2H-MoS2 /CNC 2D nanocomposites simultaneously. Interestingly, the intercalated CNC sandwiched in MoS2 nanosheets increases the interlayer spacing of 2H-MoS2 , providing perfect conditions to accommodate the large-sized ions. Therefore, these nanocomposites are good anode materials of potassium-ion batteries (KIBs), showing a high reversible capacity of 203 mAh g-1 at 200 mA g-1 after 300 cycles, a good reversible capacity of 114 mAh g-1 at 500 mA g-1 , and a low decay of 0.02% per cycle over 1500 cycles. With these impressive KIB performances, this efficient GPIE method will open up a new avenue to prepare pure-phase MoS2 and promising 2D nanocomposites for high-performance device applications.

Evaluation of the effects of an artificial intelligence system on endoscopy quality and preliminary testing of its performance in detecting early gastric cancer: a randomized controlled trial.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is a prerequisite for detecting upper gastrointestinal lesions especially early gastric cancer (EGC). An artificial intelligence system has been shown to monitor blind spots during EGD. In this study, we updated the system (ENDOANGEL), verified its effectiveness in improving endoscopy quality, and pretested its performance in detecting EGC in a multicenter randomized controlled trial. METHODS: ENDOANGEL was developed using deep convolutional neural networks and deep reinforcement learning. Patients undergoing EGD in five hospitals were randomly assigned to the ENDOANGEL-assisted group or to a control group without use of ENDOANGEL. The primary outcome was the number of blind spots. Secondary outcomes included performance of ENDOANGEL in predicting EGC in a clinical setting. RESULTS: 1050 patients were randomized, and 498 and 504 patients in the ENDOANGEL and control groups, respectively, were analyzed. Compared with the control group, the ENDOANGEL group had fewer blind spots (mean 5.38 [standard deviation (SD) 4.32] vs. 9.82 [SD 4.98]; P < 0.001) and longer inspection time (5.40 [SD 3.82] vs. 4.38 [SD 3.91] minutes; P < 0.001). In the ENDOANGEL group, 196 gastric lesions with pathological results were identified. ENDOANGEL correctly predicted all three EGCs (one mucosal carcinoma and two high grade neoplasias) and two advanced gastric cancers, with a per-lesion accuracy of 84.7 %, sensitivity of 100 %, and specificity of 84.3 % for detecting gastric cancer. CONCLUSIONS: In this multicenter study, ENDOANGEL was an effective and robust system to improve the quality of EGD and has the potential to detect EGC in real time.

Serum pepsinogen levels in different regions of China and its influencing factors: a multicenter cross-sectional study.

BACKGROUND: The aim of this study is to investigate the difference of serum pepsinogen (PG) baseline levels in different regions of China and its influencing factors. METHODS: From October 2016 to October 2018, asymptomatic health checkup people who underwent nasal endoscopy in nine health management centers in different regions of China were collected. Lifestyle questionnaires were conducted, and serum PG and gastroscopy were performed. The differences in PG levels in baseline population (OLGA-0 grade) were studied according to geographical subregions of China. SPSS software was used for statistical analysis. RESULTS: 1922 patients were included in the final analysis. Compared with the non-atrophy (OLGA-0) group, PGR levels in atrophy group (OLGA-I to IV) were significantly decreased with the atrophy degree (p < 0.05). A total of 1590 baseline people (OLGA-0) were included in the study, including 254 from South China, 574 from East China, 210 from Southwest China, 332 from Northeast China, and 220 from Central/Northern China. There were significant differences in baseline PGI levels among the five regions (p < 0.05). The PGII levels were also different among the five regions, except for Central/Northern versus Southern China. PGR (PGI/PGII ratio) levels in Southern China were higher than other four regions. Further studies were conducted on the related factors that might affect the baseline PG level, which was affected by nationality, dietary habits, smoking, Helicobacter pylori infection and other related factors. CONCLUSION: Influenced by many factors, the baseline PG levels are different in different regions of China. In the follow-up studies of PG cut-off value, different PG cut-off value based on region may be more effective in the screening of gastric cancer and precancerous lesions in China.

Laparoscopic caudate lobectomy: a multicenter, propensity score-matched report of safety, feasibility, and early outcomes.

BACKGROUND: Caudate lobectomy via laparoscopic surgery has rarely been described. This multicenter, propensity score-matched study was performed to assess the safety and efficacy of laparoscopic caudate lobectomy (LCL). METHODS: A multicenter retrospective study was performed including all patients who underwent LCL and open caudate lobectomy (OCL) in four institutions from January 2013 to December 2018. In total, 131 patients were included in this study and divided into LCL (n = 19) and OCL (n = 112) groups. LCLs were matched to OCLs (1:2) using a propensity score matching (PSM) based on nine preoperative variables, including patient demographics and tumor characteristics. The pathological results, perioperative and postoperative parameters, and short-term outcomes were compared between the two groups. RESULTS: After PSM, there were 18 and 36 patients in the LCL and OCL groups, respectively. Baseline characteristics were comparable after matching. LCL was associated with less blood (100 vs. 300 ml, respectively; P < 0.001) and a shorter postoperative stay (6.0 vs 8.0 days, respectively; P = 0.003). Most patients' resection margins were > 10 mm in the LCL group (P = 0.021), and all patients with malignancy in both groups achieved R0 resection. In terms of early postoperative outcomes, the overall morbidity rate was identical in each group (11.1% vs. 11.1%, respectively; P = 1.000). No mortality occurred in either group. CONCLUSIONS: Laparoscopy is a feasible choice for resection of tumors located in the caudate lobe with acceptable perioperative results.

Direct Observation of Huge Flexoelectric Polarization around Crack Tips.

Flexoelectricity is especially relevant for nanoscale structures, and it is expected to be largest at the tip of cracks. We demonstrate the presence of a huge flexoelectric polarization at crack tips in SrTiO3 by direct observation with scanning transmission electron microscopy. We observe an averaged polarization of 62 ± 16 µC cm-2 in the three unit cells adjacent to the crack tip, which is one of the largest flexoelectric polarizations ever reported. The polarization is screened by an electron density of 0.7 ± 0.1 e-/uc localized within one unit cell. These findings reveal the relevance of flexoelectricity for the science of crack formation and propagation.

Characterizing heterogeneity of non-small cell lung tumour microenvironment to identify signature prognostic genes.

Growing evidence has highlighted the immune response as an important feature of carcinogenesis and therapeutic efficacy in non-small cell lung cancer (NSCLC). This study focused on the characterization of immune infiltration profiling in patients with NSCLC and its correlation with survival outcome. All TCGA samples were divided into three heterogeneous clusters based on immune cell profiles: cluster 1 ('low infiltration' cluster), cluster 2 ('heterogeneous infiltration' cluster) and cluster 3 ('high infiltration' cluster). The immune cells were responsible for a significantly favourable prognosis for the 'high infiltration' community. Cluster 1 had the lowest cytotoxic activity, tumour-infiltrating lymphocytes and interferon-gamma (IFN-γ), as well as immune checkpoint molecules expressions. In addition, MHC-I and immune co-stimulator were also found to have lower cluster 1 expressions, indicating a possible immune escape mechanism. A total of 43 differentially expressed genes (DEGs) that overlapped among the groups were determined based on three clusters. Finally, based on a univariate Cox regression model, prognostic immune-related genes were identified and combined to construct a risk score model able to predict overall survival (OS) rates in the validation datasets.