Non-epitaxial single-crystal 2D material growth by geometric confinement.

Two-dimensional (2D) materials and their heterostructures show a promising path for next-generation electronics1-3. Nevertheless, 2D-based electronics have not been commercialized, owing mainly to three critical challenges: i) precise kinetic control of layer-by-layer 2D material growth, ii) maintaining a single domain during the growth, and iii) wafer-scale controllability of layer numbers and crystallinity. Here we introduce a deterministic, confined-growth technique that can tackle these three issues simultaneously, thus obtaining wafer-scale single-domain 2D monolayer arrays and their heterostructures on arbitrary substrates. We geometrically confine the growth of the first set of nuclei by defining a selective growth area via patterning SiO2 masks on two-inch substrates. Owing to substantial reduction of the growth duration at the micrometre-scale SiO2 trenches, we obtain wafer-scale single-domain monolayer WSe2 arrays on the arbitrary substrates by filling the trenches via short growth of the first set of nuclei, before the second set of nuclei is introduced, thus without requiring epitaxial seeding. Further growth of transition metal dichalcogenides with the same principle yields the formation of single-domain MoS2/WSe2 heterostructures. Our achievement will lay a strong foundation for 2D materials to fit into industrial settings.

Layer-by-layer thinning of two-dimensional materials.

Etching technology - one of the representative modern semiconductor device makers - serves as a broad descriptor for the process of removing material from the surfaces of various materials, whether partially or entirely. Meanwhile, thinning technology represents a novel and highly specialized approach within the realm of etching technology. It indicates the importance of achieving an exceptionally sophisticated and precise removal of material, layer-by-layer, at the nanoscale. Notably, thinning technology has gained substantial momentum, particularly in top-down strategies aimed at pushing the frontiers of nano-worlds. This rapid development in thinning technology has generated substantial interest among researchers from diverse backgrounds, including those in the fields of chemistry, physics, and engineering. Precisely and expertly controlling the layer numbers of 2D materials through the thinning procedure has been considered as a crucial step. This is because the thinning processes lead to variations in the electrical and optical characteristics. In this comprehensive review, the strategies for top-down thinning of representative 2D materials (e.g., graphene, black phosphorus, MoS2, h-BN, WS2, MoSe2, and WSe2) based on conventional plasma-assisted thinning, integrated cyclic plasma-assisted thinning, laser-assisted thinning, metal-assisted splitting, and layer-resolved splitting are covered in detail, along with their mechanisms and benefits. Additionally, this review further explores the latest advancements in terms of the potential advantages of semiconductor devices achieved by top-down 2D material thinning procedures.

Broadband Van-der-Waals Photodetector Driven by Ferroelectric Polarization.

The potential for various future industrial applications has made broadband photodetectors beyond visible light an area of great interest. Although most 2D van-der-Waals (vdW) semiconductors have a relatively large energy bandgap (>1.2 eV), which limits their use in short-wave infrared detection, they have recently been considered as a replacement for ternary alloys in high-performance photodetectors due to their strong light-matter interaction. In this study, a ferroelectric gating ReS2 /WSe2 vdW heterojunction-channel photodetector is presented that successfully achieves broadband light detection (>1300 nm, expandable up to 2700 nm). The staggered type-II bandgap alignment creates an interlayer gap of 0.46 eV between the valence band maximum (VBMAX ) of WSe2 and the conduction band minimum (CBMIN ) of ReS2 . Especially, the control of poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) ferroelectric dipole polarity for a specific wavelength allows a high photoresponsivity of up to 6.9 × 103 A W-1 and a low dark current below 0.26 nA under the laser illumination with a wavelength of 405 nm in P-up mode. The achieved high photoresponsivity, low dark current, and full-range near infrared (NIR) detection capability open the door for next-generation photodetectors beyond traditional ternary alloy photodetectors.

Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial.

BACKGROUND AND AIMS: The effectiveness of gemcitabine-based adjuvant chemotherapy is unclear in cholangiocarcinoma. We investigated the role of adjuvant gemcitabine plus cisplatin (GemCis) in a homogeneous group of high-risk patients with resected, lymph node-positive extrahepatic cholangiocarcinoma. APPROACH AND RESULTS: Adenocarcinoma of perihilar or distal bile duct with regional lymph node metastasis who underwent curative-intent surgery (R0/R1) was eligible. Patients were randomized to receive GemCis (gemcitabine 1000 mg/m2, cisplatin 25 mg/m2 on days 1 and 8) or capecitabine (1250 mg/m2 twice daily on days 1-14) every 3 weeks for 8 cycles. Primary endpoint was disease-free survival. Secondary endpoints were overall survival and safety. All p values are 1 sided and were considered significant if <0.1. Between July 2017 and November 2020, 101 patients (50 in the GemCis and 51 in the capecitabine group) were included in the intention-to-treat population. Perihilar and distal bile ducts were the primary sites in 45 (44.6%) and 56 (55.4%) patients, respectively, and 32 (31.7%) had R1 resections. Median (1-sided 90% CI) follow-up duration was 33.4 (30.5-35.8) months. In the GemCis and capecitabine group, 2-year disease-free survival rates were 38.5% (29.5%-47.4%) and 25.1% (17.4%-33.5%) [HR=0.96 (CI, 0.71-1.30), p=0.430], and median overall survival was 35.7 months (29.5-not estimated) and 35.7 months (30.9-not estimated) [HR=1.08 (CI, 0.71-1.64), 1-sided p=0.404], respectively. Grade 3-4 adverse events occurred in 42 (84.0%) and 8 patients (16.0%) in the GemCis and capecitabine groups, respectively. No treatment-related deaths were reported. CONCLUSIONS: In resected lymph node-positive extrahepatic cholangiocarcinoma, adjuvant GemCis did not improve survival outcomes compared with capecitabine.

Clinical outcomes of second-line therapy following disease progression on first-line modified FOLFIRINOX for borderline resectable and locally advanced pancreatic adenocarcinoma.

BACKGROUND: Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS: Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS: With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS: The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.

Dynamic liver volume change in predicting hepatic decompensation and long-term effects of stereotactic body radiation therapy.

BACKGROUND AND AIM: This study aimed to investigate the association between liver volume change and hepatic decompensation and compare the risk of hepatic decompensation in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) who underwent stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of SBRT-treated HCC and compensated LC without HCC patients was conducted. Liver volume was measured using auto-segmentation software on liver dynamic computed tomography scans. The decompensation event was defined as the first occurrence of refractory ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. We evaluated the association between the rate of liver volume decrease and hepatic decompensation and compared decompensation events between the SBRT and LC cohorts using propensity score matching. RESULTS: A total of 138 patients from the SBRT cohort and 488 from the LC cohort were analyzed. The rate of liver volume decrease was associated with the risk of decompensation events in both cohorts. The 3-year rate of decompensation events was significantly higher in the group with a liver volume decreasing rate > 7%/year compared with the group with a rate < 7%/year. In the propensity score-matched cohort, the 3-year rate of decompensation events after a single session of SBRT was not significantly different from that in the LC cohort. CONCLUSIONS: The rate of liver volume decrease was significantly associated with the risk of hepatic decompensation in both HCC patients who received SBRT and LC patients. A single session of SBRT for HCC did not result in a higher decompensation rate compared with LC.

Nonlinear Transport due to Magnetic-Field-Induced Flat Bands in the Nodal-Line Semimetal ZrTe_{5}.

The Dirac material ZrTe_{5} at very low carrier density was recently found to be a nodal-line semimetal, where ultraflat bands are expected to emerge in magnetic fields parallel to the nodal-line plane. Here, we report that in very low carrier-density samples of ZrTe_{5}, when the current and the magnetic field are both along the crystallographic a axis, the current-voltage characteristics presents a pronounced nonlinearity which tends to saturate in the ultra quantum limit. The magnetic-field dependence of the nonlinear coefficient is well explained by the Boltzmann theory for flat-band transport, and we argue that this nonlinear transport is likely due to the combined effect of flat bands and charge puddles; the latter appear due to very low carrier densities.

The SLC26A9 inhibitor S9-A13 provides no evidence for a role of SLC26A9 in airway chloride secretion but suggests a contribution to regulation of ASL pH and gastric proton secretion.

The solute carrier 26 family member A9 (SLC26A9) is an epithelial anion transporter that is assumed to contribute to airway chloride secretion and surface hydration. Whether SLC26A9 or CFTR is responsible for airway Cl- transport under basal conditions is still unclear, due to the lack of a specific inhibitor for SLC26A9. In the present study, we report a novel potent and specific inhibitor for SLC26A9, identified by screening of a drug-like molecule library and subsequent chemical modifications. The most potent compound S9-A13 inhibited SLC26A9 with an IC50 of 90.9 ± 13.4 nM. S9-A13 did not inhibit other members of the SLC26 family and had no effects on Cl- channels such as CFTR, TMEM16A, or VRAC. S9-A13 inhibited SLC26A9 Cl- currents in cells that lack expression of CFTR. It also inhibited proton secretion by HGT-1 human gastric cells. In contrast, S9-A13 had minimal effects on ion transport in human airway epithelia and mouse trachea, despite clear expression of SLC26A9 in the apical membrane of ciliated cells. In both tissues, basal and stimulated Cl- secretion was due to CFTR, while acidification of airway surface liquid by S9-A13 suggests a role of SLC26A9 for airway bicarbonate secretion.

Mini-implant mandibular overdentures under a two-step immediate loading protocol: A 4-6-year retrospective study.

OBJECTIVES: This retrospective study to evaluate the treatment outcomes of mandibular mini-implant overdentures (MIODs) placed under a two-step immediate loading protocol. BACKGROUND: The mini-implant overdenture emphasises the advantages of simplicity using flapless surgery and immediate loading. However, some mini-implant have lowe initial stability. MATERIALS AND METHODS: A total of 30 participants who used mandibular MIODs and maxillary removable complete dentures (RCDs) over 4 years were included. Four one-piece mini-implants (<3 mm in diameter) were placed by a flapless surgical approach after fabrication of new RCDs, and the O-ring attachment was attached at least 8 weeks after implant placement. RESULTS: The average observation period was 58.9 ± 9.2 months after mini-implant loading. The survival rate of the implants was 100.0%, and the overall change in mean marginal bone level (ΔMBL) was -0.9 ± 1.1 mm. The implant success rate was 83.3% at the implant level, and 66.7% at the patient level. The mean initial Periotest value was 0.9 ± 3.1, and it was positively associated with ΔMBL and implant success (P < .05). Patient satisfaction improved after conversion from RCDs to MIODs (P < .05), and mastication and pain showed greater satisfaction with longer loading time (P < .05). CONCLUSIONS: The mandibular MIODs could be chosen as an alternative treatment under a two-step immediate-loading protocol in edentulous patients with limited alveolar bone volume. To ensure superior treatment outcomes of MIODs, initial stability of implant must be obtained using as wide a diameter as possible within the anatomically allowable limits.

Narrow-diameter versus regular-diameter dental implants for mandibular overdentures: A systematic review and meta-analysis.

PURPOSE: The aim of this systematic review was to compare treatment outcomes in terms of implant survival rate, marginal bone loss, and patient-reported outcome measures (PROMs) between narrow-diameter implants and regular-diameter implants (RDIs) for mandibular implant overdentures (MIOs). METHODS: This study was based on the methodology adapted as per Cochrane. Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched for pertinent studies published by July 22, 2022. Outcome parameters included in this meta-analysis were implant survival rate, marginal bone loss, visual analogue scale score for patient satisfaction, and value of oral health impact profile. RESULTS: A total of 782 non-duplicate articles and 83 clinical study registrations were identified from database and hand searches, of which 26 were eligible for full-text searches. Finally, 12 publications reporting on 8 independent studies were included in this review. In the meta-analysis, implant survival rate and marginal bone loss did not significantly differ between narrow-diameter implants and RDIs. Regarding RDIs, narrow-diameter implants were associated with significantly better outcomes in general patient satisfaction and oral health-related quality of life than RDIs for mandibular overdentures. CONCLUSIONS: Narrow-diameter implants have competitive treatment outcomes compared to RDIs in terms of implant survival rate, marginal bone loss, and PROMs. [Correction added on July 21, 2023, after first online publication: The abbreviation RDIs was changed to PROMs in the preceding sentence.] Thus, narrow-diameter implants might be an alternative treatment option for MIOs in situations with limited alveolar bone volume.

Stability of Floquet Majorana Box Qubits.

In one-dimensional topological superconductors driven periodically with the frequency ω, two types of topological edge modes may appear, the well-known Majorana zero mode and a Floquet Majorana mode located at the quasienergy ℏω/2. We investigate two Josephson-coupled topological quantum wires in the presence of Coulomb interactions, forming a so-called Majorana box qubit. An oscillating gate voltage can induce Floquet Majorana modes in both wires. This allows for the encoding of three qubits in a sector with fixed electron parity. If such a system is prepared by increasing the amplitude of oscillations adiabatically, it is inherently unstable as interactions resonantly create quasiparticles. This can be avoided by using instead a protocol where the oscillation frequency is increased slowly. In this case, one can find a parameter regime where the system remains stable.

Gigantic Magnetochiral Anisotropy in the Topological Semimetal ZrTe_{5}.

Topological materials with broken inversion symmetry can give rise to nonreciprocal responses, such as the current rectification controlled by magnetic fields via magnetochiral anisotropy. Bulk nonreciprocal responses usually stem from relativistic corrections and are always very small. Here we report our discovery that ZrTe_{5} crystals in proximity to a topological quantum phase transition present gigantic magnetochiral anisotropy, which is the largest ever observed to date. We argue that a very low carrier density, inhomogeneities, and a torus-shaped Fermi surface induced by breaking of inversion symmetry in a Dirac material are central to explain this extraordinary property.

Stereotactic body radiation therapy as a salvage treatment for single viable hepatocellular carcinoma at the site of incomplete transarterial chemoembolization: a retrospective analysis of 302 patients.

BACKGROUND: To evaluate the clinical outcomes of patients who received stereotactic body radiation therapy (SBRT) for single viable hepatocellular carcinoma (HCC) at the site of incomplete transarterial chemoembolization (TACE). METHODS: Patients treated with SBRT for single viable HCC after incomplete TACE between 2012 and 2017 at Asan Medical Center (Seoul, South Korea) were included. Incomplete TACE was defined as (1) evidence of viable HCC at the site of TACE on follow-up dynamic computed tomography (CT) or magnetic resonance imaging following one or more consecutive TACEs, (2) no definite tumor staining on superselective hepatic angiogram, or (3) no definite iodized oil uptake on post-embolization angiogram or CT. Doses of 10-15 Gy per fraction were given over 3-4 consecutive days. The primary outcome was local control rate at 3 years and secondary outcome included tumor response, overall survival rate, out-of-field intrahepatic recurrence-free survival, distant metastasis-free survival and treatment-related toxicities. Treatment-related adverse events were evaluated according to the common terminology criteria for adverse events, version 4.03. RESULTS: A total of 302 patients were analyzed. The median follow-up duration was 32.9 months (interquartile range [IQR], 23.6-41.7) and the median tumor size was 2.0 cm (range, 0.7-6.9). The local control (LC) and overall survival rates at 3 years were 91.2 and 72.7%, respectively. 95.4% of the tumors reached complete response (CR) during the entire follow-up period (anyCR). The median interval from SBRT to anyCR was 3.4 months (IQR, 1.9-4.7), and 39.9 and 83.3% of the lesions reached CR at 3- and 6-months after SBRT, respectively. Radiation-induced liver disease was observed in 8 (2.6%) patients. No patients experienced gastroduodenal bleeding within the radiation field. CONCLUSION: SBRT could be considered a feasible salvage treatment option for HCC after incomplete TACE.

Novel CFTR Activator Cact-3 Ameliorates Ocular Surface Dysfunctions in Scopolamine-Induced Dry Eye Mice.

Cystic fibrosis transmembrane conductance regulator (CFTR) is highly expressed on the ocular epithelium and plays a pivotal role in the fluid secretion driven by chloride transport. Dry eye disease is one of the most common diseases with limited therapeutic options. In this study, a high-throughput screening was performed to identify novel CFTR activators capable of inducing chloride secretion on the ocular surface. The screening of 50,000 small molecules revealed three novel CFTR activators. Among them, the most potent CFTR activator, Cact-3 (7-(3,4-dimethoxyphenyl)-N-(4-ethoxyphenyl)pyrazolo [1,5-α]pyrimidine-2-carboxamide), produced large and sustained Cl- currents in WT-CFTR-expressing FRT cells with no alterations of ANO1 and hERG channel activity. The application of Cact-3 strongly activated CFTR in the ocular epithelia of mice and it also significantly increased CFTR-mediated Cl- transport in a primary cultured human conjunctival epithelium. Cact-3 strongly stimulated tear secretion in normal mice. In addition, Cact-3 significantly reduced ocular surface damage and the expression of proinflammatory factors, including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in an experimental mouse model of dry eye disease. These results suggest that Cact-3, a novel CFTR activator, may be a potential development candidate for the treatment of dry eye disease.

Accuracy of implant impression techniques with a scannable healing abutment.

STATEMENT OF PROBLEM: Scannable healing abutments are a convenient option to facilitate impression making for implant-supported restorations. However, studies evaluating the accuracy of the impression technique with scannable healing abutments are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the accuracy of implant impression techniques with scannable healing abutments. MATERIALS AND METHODS: A partially edentulous mandibular dentiform model was fabricated with an epoxy resin, and implants were placed in the mandibular right second premolar and first molar areas. A maxillary dentiform model was then fabricated, and both models were mounted on an articulator. Scan data were obtained from the mounted models and set as the reference scans. The experimental models were divided into 4 groups (n=10). The conventional pick-up impression technique and definitive casts were used in group CI. The scan data from the definitive casts were obtained with a 3D model scanner. An intraoral scanner with a digital body scan was used in group DS. Group MS yielded definitive casts with dual-arch impressions with scannable healing abutments. The fabricated definitive casts were mounted and scanned with a 3D cast scanner. Intraoral scanning with scannable healing abutments was used in group IS. In all 4 groups, the interarch relationship in the maximum intercuspal position was obtained by scanning the facial aspect. The center of the implant head was set as a measurement point for linear intra-arch deviations and implant angle deviations. The mesiopalatal cusp tip of the maxillary right first molar was used to calibrate the linear interarch deviations. The data obtained from each group were compared with the data from the reference scan. As the data were not normally distributed, the Kruskal-Wallis test and Bonferroni correction were used for the analysis (α=.05). RESULTS: Group MS exhibited significantly higher deviations in linear intra-arch and implant angles compared with the other groups (P<.05). No significant difference was found between the groups in linear interarch deviations (P>.05). CONCLUSIONS: The accuracy of intraoral scanning with scannable healing abutments was comparable with that of conventional pick-up impression techniques and digital scans with scan bodies. However, model scanning with scannable healing abutments may not be clinically acceptable for implant impressions.

Two-Dimensional MXene Synapse for Brain-Inspired Neuromorphic Computing.

MXenes, an emerging class of two-dimensional (2D) transition metal carbides and nitrides, have attracted wide attention because of their fascinating properties required in functional electronics. Here, an atomic-switch-type artificial synapse fabricated on Ti3 C2 Tx MXene nanosheets with lots of surface functional groups, which successfully mimics the dynamics of biological synapses, is reported. Through in-depth analysis by X-ray photoelectron spectroscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, it is found that the synaptic dynamics originated from the gradual formation and annihilation of the conductive metallic filaments on the MXene surface with distributed functional groups. Subsequently, via training and inference tasks using a convolutional neural network for the Canadian-Institute-For-Advanced-Research-10 dataset, the applicability of the artificial MXene synapse to hardware neural networks is demonstrated.

Role of palliative radiotherapy in bleeding control in patients with unresectable advanced gastric cancer.

BACKGROUND: This study analyzed the clinical results of palliative radiotherapy for bleeding control in patients with unresectable advanced gastric cancer. METHODS: We retrospectively reviewed the medical records of patients who met the following inclusion criteria between January 2002 and June 2018: histologically proven gastric cancer, gastric tumor bleeding confirmed by upper gastrointestinal endoscopy, and palliative radiotherapy performed for hemostasis. The median radiotherapy dose was 30 Gy, with a daily dose ranging from 1.8 to 3 Gy. RESULTS: Sixty-one patients were included in this analysis. The study population was predominantly male (72.1%), with a median age of 62 years (range: 32-92). The median baseline hemoglobin level was 7.1 g/dL, and the most common presenting symptom of gastric tumor bleeding was melena (85.2%). Bleeding control was achieved in 54 (88.5%) patients. The median levels of hemoglobin at 1, 2, and 3 months after completion of radiotherapy were 10.1 g/dL, 10.2 g/dL, and 10.4 g/dL, respectively; these values were significantly different from that before radiotherapy (7.1 g/dL; p < 0.001). The median overall survival was 4.8 months. Among the 54 patients who achieved bleeding control after radiotherapy, 19 (35.2%) experienced re-bleeding during the follow-up period. The median time to re-bleeding was 6.0 months. Multivariate analysis demonstrated that a higher radiation dose (p = 0.007) and additional chemotherapy after radiotherapy (p = 0.004) were significant factors for prolonging the time to re-bleeding. CONCLUSIONS: Tumor bleeding was adequately controlled by radiotherapy in patients with unresectable advanced gastric cancer.

Radiofrequency ablation versus stereotactic body radiation therapy for small (≤ 3 cm) hepatocellular carcinoma: A retrospective comparison analysis.

BACKGROUND AND AIM: We compared the clinical outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) in small (≤ 3 cm) hepatocellular carcinoma. METHODS: A total of 266 patients treated with RFA (n = 179) or SBRT (n = 87) were reviewed. Local control rates (LCRs), intrahepatic recurrence-free survival (IHRFS) rates, and overall survival (OS) rates were compared. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline characteristics between the two groups. RESULTS: The median follow-up period was 50.3 months, and treatment method (RFA vs SBRT) was not a significant prognostic factor for LCR, OS, and IHRFS in both multivariate and IPTW-adjusted analyses. The 4-year LCRs after RFA and SBRT were 92.7% and 95.0%, respectively. Perivascular location was a significant prognostic factor for LCR in the entire patients and in the RFA group, but not in the SBRT group. The 4-year OS rates in the RFA and SBRT groups were 78.1% and 64.1%, respectively (P = 0.012). After IPTW adjustment, the 4-year LCRs (90.6% vs 96.3%) and OS rates (71.8% vs 70.2%) were not significantly different between the two groups. The rate of grade ≥ 3 adverse events was 0.6% (n = 1) in the RFA group and 1.1% (n = 1) in the SBRT group. CONCLUSIONS: The two treatment methods showed comparable outcomes in terms of LCR, OS rate, and IHRFS rate after IPTW adjustment. SBRT seems to be a viable alternative method for small hepatocellular carcinomas that are not suitable for RFA due to tumor location.

Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice.

Dry eye disease is one of the most common diseases, with increasing prevalence in many countries, but treatment options are limited. Cystic fibrosis transmembrane conductance regulator (CFTR) is a major ion channel that facilitates fluid secretion in ocular surface epithelium and is a potential target of therapeutic agent for the treatment of dry eye disease. In this study, we performed a cell-based, high-throughput screening for the identification of novel natural products that activate CFTR and restore the aqueous deficiency in dry eye. Screening of 1000 natural products revealed isorhamnetin, a flavonol aglycone, as a novel CFTR activator. Electrophysiological studies showed that isorhamnetin significantly increased CFTR chloride current, both wild type and ∆F508-CFTR. Isorhamnetin did not alter intracellular cAMP levels and the activity of other ion channels, including ANO1, ENaC, and hERG. Notably, application of isorhamnetin on mouse ocular surface induced CFTR activation and increased tear volume. In addition, isorhamnetin significantly reduced ocular surface damage and expression of interleukin (IL)-1ß, IL-8, and tumor necrosis factor (TNF)-α in an experimental mouse model of dry eye. These data suggest that isorhamnetin may be used to treat dry eye disease.

Transcriptome Analysis Reveals HgCl2 Induces Apoptotic Cell Death in Human Lung Carcinoma H1299 Cells through Caspase-3-Independent Pathway.

Mercury is one of the detrimental toxicants that can be found in the environment and exists naturally in different forms; inorganic and organic. Human exposure to inorganic mercury, such as mercury chloride, occurs through air pollution, absorption of food or water, and personal care products. This study aimed to investigate the effect of HgCl2 on cell viability, cell cycle, apoptotic pathway, and alters of the transcriptome profiles in human non-small cell lung cancer cells, H1299. Our data show that HgCl2 treatment causes inhibition of cell growth via cell cycle arrest at G0/G1- and S-phase. In addition, HgCl2 induces apoptotic cell death through the caspase-3-independent pathway. Comprehensive transcriptome analysis using RNA-seq indicated that cellular nitrogen compound metabolic process, cellular metabolism, and translation for biological processes-related gene sets were significantly up- and downregulated by HgCl2 treatment. Interestingly, comparative gene expression patterns by RNA-seq indicated that mitochondrial ribosomal proteins were markedly altered by low-dose of HgCl2 treatment. Altogether, these data show that HgCl2 induces apoptotic cell death through the dysfunction of mitochondria.