Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid.

Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache and neuroinflammatory or cerebrovascular disease. These conditions-termed here as Neuro-COVID-are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared with patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared with mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.

CEP120-mediated KIAA0753 recruitment onto centrioles is required for timely neuronal differentiation and germinal zone exit in the developing cerebellum.

Joubert syndrome (JS) is a recessive ciliopathy in which all affected individuals have congenital cerebellar vermis hypoplasia. Here, we report that CEP120, a JS-associated protein involved in centriole biogenesis and cilia assembly, regulates timely neuronal differentiation and the departure of granule neuron progenitors (GNPs) from their germinal zone during cerebellar development. Our results show that depletion of Cep120 perturbs GNP cell cycle progression, resulting in a delay of cell cycle exit in vivo. To dissect the potential mechanism, we investigated the association between CEP120 interactome and the JS database and identified KIAA0753 (a JS-associated protein) as a CEP120-interacting protein. Surprisingly, we found that CEP120 recruits KIAA0753 to centrioles, and that loss of this interaction induces accumulation of GNPs in the germinal zone and impairs neuronal differentiation. Importantly, the replenishment of wild-type CEP120 rescues the above defects, whereas expression of JS-associated CEP120 mutants, which hinder KIAA0753 recruitment, does not. Together, our data reveal a close interplay between CEP120 and KIAA0753 for the germinal zone exit and timely neuronal differentiation of GNPs during cerebellar development, and mutations in CEP120 and KIAA0753 may participate in the heterotopia and cerebellar hypoplasia observed in JS patients.

Advancing carbohydrate quantification in MALDI mass spectrometry by the rapidly freeze-drying droplet (RFDD) method.

Quantitative carbohydrate analysis faces challenges in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), including insufficient sensitivity and inconsistent spatial distribution of ion intensity. This study introduces an innovative sample preparation approach, the Rapidly Freeze-Drying Droplet (RFDD) method, aimed at overcoming these challenges by enhancing the homogeneity of the sample morphology and signal intensity in MALDI. Compared to conventional preparation methods, the RFDD method reduces the laser energy threshold and demonstrates a remarkable increase in signal intensity for carbohydrates, facilitating the detection of high-molecular-weight polysaccharides (>10 kDa). The RFDD-prepared samples exhibit a uniformly distributed signal intensity that overcomes the 'sweet spot' issue in MALDI. The enhanced signal intensity and reproducibility lead to reliable quantitative analysis of carbohydrates, eliminating the need for expensive isotopic standards in each sample. A straightforward and accessible approach is presented for general laboratories, revolutionizing carbohydrate analysis in MALDI-MS.

Bcl6 controls meningeal Th17-B cell interaction in murine neuroinflammation.

Ectopic lymphoid tissue containing B cells forms in the meninges at late stages of human multiple sclerosis (MS) and when neuroinflammation is induced by interleukin (IL)-17 producing T helper (Th17) cells in rodents. B cell differentiation and the subsequent release of class-switched immunoglobulins have been speculated to occur in the meninges, but the exact cellular composition and underlying mechanisms of meningeal-dominated inflammation remain unknown. Here, we performed in-depth characterization of meningeal versus parenchymal Th17-induced rodent neuroinflammation. The most pronounced cellular and transcriptional differences between these compartments was the localization of B cells exhibiting a follicular phenotype exclusively to the meninges. Correspondingly, meningeal but not parenchymal Th17 cells acquired a B cell-supporting phenotype and resided in close contact with B cells. This preferential B cell tropism for the meninges and the formation of meningeal ectopic lymphoid tissue was partially dependent on the expression of the transcription factor Bcl6 in Th17 cells that is required in other T cell lineages to induce isotype class switching in B cells. A function of Bcl6 in Th17 cells was only detected in vivo and was reflected by the induction of B cell-supporting cytokines, the appearance of follicular B cells in the meninges, and of immunoglobulin class switching in the cerebrospinal fluid. We thus identify the induction of a B cell-supporting meningeal microenvironment by Bcl6 in Th17 cells as a mechanism controlling compartment specificity in neuroinflammation.

Association between pain and cognitive and daily functional impairment in older institutional residents: a cross-sectional study.

BACKGROUND: Pain is often neglected in disabled older population, especially in Taiwan where the population of institutional residents is rapidly growing. Our study aimed to investigate pain prevalence and associated factors among institutional residents to improve pain assessment and management. METHODS: This nationwide study recruited 5,746 institutional residents in Taiwan between July 2019 and February 2020. Patient self-report was considered the most valid and reliable indicator of pain. A 5-point verbal rating scale was used to measure pain intensity, with a score ranging from 2 to 5 indicating the presence of pain. Associated factors with pain, including comorbidities, functional dependence, and quality of life, were also assessed. RESULTS: The mean age of the residents was 77.1 ± 13.4 years, with 63.1% of them aged over 75 years. Overall, 40.3% of the residents reported pain, of whom 51.2% had moderate to severe pain. Pain was more common in residents with comorbidities and significantly impacted emotions and behavior problems, and the mean EQ5D score, which is a measure of health-related quality of life (p < .001). Interestingly, pain was only related to instrumental activities of daily living (IADL) and not activities of daily living (ADL). On the other hand, dementia was significantly negatively associated with pain (p < .001), with an estimated odds of 0.63 times (95% CI: 0.53-0.75) for the presence of pain when compared to residents who did not have dementia. CONCLUSIONS: Unmanaged pain is common among institutional residents and is associated with comorbidities, IADL, emotional/behavioral problems, and health-related quality of life. Older residents may have lower odds of reporting pain due to difficulty communicating their pain, even through the use of a simple 5-point verbal rating scale. Therefore, more attention and effort should be directed towards improving pain evaluation in this vulnerable population .

Hyperbaric Oxygen Therapy Alleviates Paclitaxel-Induced Peripheral Neuropathy Involving Suppressing TLR4-MyD88-NF-κB Signaling Pathway.

Paclitaxel (PAC) results in long-term chemotherapy-induced peripheral neuropathy (CIPN). The coexpression of transient receptor potential vanilloid 1 (TRPV1) and Toll-like receptor 4 (TLR4) in the nervous system plays an essential role in mediating CIPN. In this study, we used a TLR4 agonist (lipopolysaccharide, LPS) and a TLR4 antagonist (TAK-242) in the CIPN rat model to investigate the role of TLR4-MyD88 signaling in the antinociceptive effects of hyper-baric oxygen therapy (HBOT). All rats, except a control group, received PAC to induce CIPN. Aside from the PAC group, four residual groups were treated with either LPS or TAK-242, and two of them received an additional one-week HBOT (PAC/LPS/HBOT and PAC/TAK-242/HBOT group). Mechanical allodynia and thermal hyperalgesia were then assessed. The expressions of TRPV1, TLR4 and its downstream signaling molecule, MyD88, were investigated. The mechanical and thermal tests revealed that HBOT and TAK-242 alleviated behavioral signs of CIPN. Immunofluorescence in the spinal cord dorsal horn and dorsal root ganglion revealed that TLR4 overexpression in PAC- and PAC/LPS-treated rats was significantly downregulated after HBOT and TAK-242. Additionally, Western blots showed a significant reduction in TLR4, TRPV1, MyD88 and NF-κB. Therefore, we suggest that HBOT may alleviate CIPN by modulating the TLR4-MyD88-NF-κB pathway.

Multimodal Analgesia with Local Wound Infiltration and Intravenous Parecoxib for Thyroidectomy.

Background and objective: Adequate postoperative pain control is an important component to enhance recovery. Multimodal analgesia with various pain control techniques has been widely used to alleviate postoperative pain. The use of either wound infiltration or a superficial cervical plexus block has been reported to be effective for pain management after thyroid surgery. The present study evaluated the effect of multimodal analgesia using lidocaine wound infiltration combined with intravenous parecoxib for patients monitored after thyroidectomy. Materials and Methods: A total of 101 patients with a multimodal analgesia protocol being monitored after thyroidectomy were enrolled. After the induction of anesthesia, multimodal analgesia was performed through wound infiltration of 1% lidocaine and epinephrine at a ratio of 1:200,000 (5 µg/mL) combined 40 mg intravenous parecoxib before skin excision. Patients were divided into two groups for this retrospective analysis based on the injection dose of lidocaine they received. Patients in Group I (the control, n = 52) received a 5 mL injection solution, while those in Group II (the study, n = 49) received a 10 mL dosage in a time-sequential manner, in accordance with a previous clinical trial. The primary outcome was measuring postoperative pain intensity at rest, as well as during motion and coughing, which was measured at the postoperative anesthetic care unit (PACU) and on the first day after the operation (POD 1) in the ward. Pain intensity was assessed using a numerical rating scale (NRS). The secondary outcomes were postoperative adverse events including anesthetic-related side effects, as well as airway and pulmonary complications. Results: Most of the patients reported no pain or mild pain during the observation period. The patients in Group II had a lower pain intensity during motion than Group I (NRS 1.47 ± 0.89 vs. 1.85 ± 0.96, p = 0.043) when measured at the postoperative anesthetic care unit. Pain intensity during coughing was also significantly lower in the study group than in the control group (NRS 1.61 ± 0.95 vs. 1.96 ± 0.79, p = 0.049) when measured at the postoperative anesthetic care unit. There were no severe adverse events in either of the groups. Only one patient (1.9%) in Group I experienced temporary vocal palsy. Conclusions: The use of lidocaine with an equal volume of intravenous parecoxib provided comparable analgesia with minimal adverse events when monitoring thyroidectomy.

Integrated single-cell transcriptomics of cerebrospinal fluid cells in treatment-naïve multiple sclerosis.

Multiple sclerosis (MS) is a chronic and often disabling autoimmune disease of the central nervous system (CNS). Cerebrospinal fluid (CSF) surrounds and protects the CNS. Analysis of CSF can aid the diagnosis of CNS diseases, help to identify the prognosis, and underlying mechanisms of diseases. Several recent studies have leveraged single-cell RNA-sequencing (scRNA-seq) to identify MS-associated changes in CSF cells that are considerably more altered than blood cells in MS. However, not all alterations were replicated across all studies. We therefore integrated multiple available scRNA-seq datasets of CSF cells from MS patients with early relapsing-remitting (RRMS) disease. We provide a searchable and interactive resource of this integrated analysis ( https://CSFinMS.bxgenomics.com ) facilitating diverse visualization and analysis methods without requiring computational skills. In the present joint analysis, we replicated the known expansion of B lineage and the recently described expansion of natural killer (NK) cells and some cytotoxic T cells and decrease of monocytes in the CSF in MS. The previous observation of the abundance of Th1-like Th17 effector memory cells in the CSF was not replicated. Expanded CSF B lineage cells resembled class-switched plasmablasts/-cells (e.g., SDC1/CD138, MZB1) as expected. Our integrative analysis thus validates increased cell type diversity and B cell maturation in the CSF in MS and improves accessibility of available data.

Hexamethyldisilazane-Mediated Amidination of Sulfonamides and Amines with Formamides.

Hexamethyldisilazane was reacted with formamides to generate N,N-disubstituent formimidamide, after which a reaction with sulfonamides was induced to form sulfonylformamidines. This protocol can be applied for arylformamidine formation in which anilines are used as substrates under optimized conditions. The advantages of this method are high efficiency, structural diversity in products with good yields, and applicability in large-scale operations.

Access to Monomeric Lead(II) Hydrides with Remarkable Thermostability and Their Use in Catalytic Hydroboration of Carbonyl Derivatives.

We report on the remarkable stability of unprecedented, monomeric lead(II) hydrides M+[LPb(II)H]- (M[1-H]), where L = 2,6-bis(3,5-diphenylpyrrolyl)pyridine and M = (18-crown-6)potassium or ([2.2.2]-cryptand)potassium. The half-life of [K18c6][1-H] of ∼2 days in tetrahydrofuran at 25 °C is significantly longer than those reported for dimeric lead(II) hydrides supported by bulky terphenyl ligands (few hours at low temperatures), which are the only examples known for lead(II) hydride compounds. The presence of a Pb-H bond in [1-H]- was unambiguously identified by multinuclear NMR spectroscopy. Remarkably, a 1H resonance of the hydride ligand was found at δ = 41.43 ppm (1JPbH = 1312 Hz). For reactivity study, [1-H]- serves as an excellent hydroboration catalyst with high turnover numbers and turnover frequencies for several carbonyl compounds.

(-)-Agelasidine A Induces Endoplasmic Reticulum Stress-Dependent Apoptosis in Human Hepatocellular Carcinoma.

Liver cancers, such as hepatocellular carcinoma (HCC), are a highly prevalent cause of cancer-related deaths. Current treatments to combat liver cancer are limited. (-)-Agelasidine A, a compound isolated from the methanol extract of Agelasnakamurai, a sesquiterpene guanidine derived from sea sponge, has antibacterial activity. We demonstrated its anticancer capabilities by researching the associated mechanism of (-)-agelasidine A in human liver cancer cells. We found that (-)-agelasidine A significantly reduced viability in Hep3B and HepG2 cells, and we determined that apoptosis was involved in the (-)-agelasidine A-induced Hep3B cell deaths. (-)-Agelasidine A activated caspases 9, 8, and 3, as well as PARP. This effect was reversed by caspase inhibitors, suggesting caspase-mediated apoptosis in the (-)-agelasidine A-treated Hep3B cells. Moreover, the reduced mitochondrial membrane potential (MMP) and the release of cytochrome c indicated that the (-)-agelasidine A-mediated mitochondrial apoptosis was mechanistic. (-)-Agelasidine A also increased apoptosis-associated proteins (DR4, DR5, FAS), which are related to extrinsic pathways. These events were accompanied by an increase in Bim and Bax, proteins that promote apoptosis, and a decrease in the antiapoptotic protein, Bcl-2. Furthermore, our results presented that (-)-agelasidine A treatment bridged the intrinsic and extrinsic apoptotic pathways. Western blot analysis of Hep3B cells treated with (-)-agelasidine A showed that endoplasmic reticulum (ER) stress-related proteins (GRP78, phosphorylated PERK, phosphorylated eIF2α, ATF4, truncated ATF6, and CHOP) were upregulated. Moreover, 4-PBA, an ER stress inhibitor, could also abrogate (-)-agelasidine A-induced cell viability reduction, annexin V+ apoptosis, death receptor (DR4, DR5, FAS) expression, mitochondrial dysfunction, and cytochrome c release. In conclusion, by activating ER stress, (-)-agelasidine A induced the extrinsic and intrinsic apoptotic pathways of human HCC.

Spinal Irisin Gene Delivery Attenuates Burn Injury-Induced Muscle Atrophy by Promoting Axonal Myelination and Innervation of Neuromuscular Junctions.

Muscle loss and weakness after a burn injury are typically the consequences of neuronal dysregulation and metabolic change. Hypermetabolism has been noted to cause muscle atrophy. However, the mechanism underlying the development of burn-induced motor neuropathy and its contribution to muscle atrophy warrant elucidation. Current therapeutic interventions for burn-induced motor neuropathy demonstrate moderate efficacy and have side effects, which limit their usage. We previously used a third-degree burn injury rodent model and found that irisin-an exercise-induced myokine-exerts a protective effect against burn injury-induced sensory and motor neuropathy by attenuating neuronal damage in the spinal cord. In the current study, spinal irisin gene delivery was noted to attenuate burn injury-induced sciatic nerve demyelination and reduction of neuromuscular junction innervation. Spinal overexpression of irisin leads to myelination rehabilitation and muscular innervation through the modulation of brain-derived neurotrophic factor and glial-cell-line-derived neurotrophic factor expression along the sciatic nerve to the muscle tissues and thereby modulates the Akt/mTOR pathway and metabolic derangement and prevents muscle atrophy.

Longitudinal Effects of a Combined Program of Pelvic Floor Muscle Training and Yoga on Genitourinary Symptoms in Asian Women of Older Age: A Randomized Experimental Study.

This parallel-two-group randomized experimental study including a supervised group and an unsupervised group examined the longitudinal effects of pelvic floor muscle training (PFMT) combined with yoga on genitourinary symptoms and the health-related quality of life (HRQOL), and compared practice adherence rates of the two groups. A sample of women experiencing ≥1 genitourinary symptom(s) were recruited and assigned to a supervised group or an unsupervised group. The supervised group attended supervised group practice sessions and performed at-home practice of PFMT and yoga. The unsupervised group performed at-home practice of PFMT and yoga. Information was collected at five time points (n = 91). Generalized estimating equation procedures were used to examine the intervention effects. An independent t-test was conducted to compare the practice adherence rates. Both groups' genitourinary symptoms and HRQOL significantly improved over time. The supervised group displayed greater improvements in genitourinary symptoms and HRQOL and better adherence than did the unsupervised group.

Optimization of Intraoperative Neural Monitoring of the Recurrent Laryngeal Nerve in Thyroid Surgery.

The application of intraoperative neural monitoring (IONM) has been widely accepted to improve surgical outcomes after thyroid surgery. The malfunction of an IONM system might interfere with surgical procedures. Thus, the development of anesthesia modalities aimed at ensuring functional neuromonitoring is essential. Two key issues should be taken into consideration for anesthetic management. Firstly, most patients undergo recurrent laryngeal nerve monitoring via surface electrodes embedded in an endotracheal tube. Thus, advanced video-assisted devices might optimize surface electrode positioning for improved neuromonitoring signaling accuracy. Secondly, neuromuscular blocking agents are routinely used during thyroid surgery. The ideal neuromuscular block should be deep enough for surgical relaxation at excision and recovered enough for an adequate signal f nerve stimulation. Proper neuromuscular block management could be achieved by titration doses of muscle relaxants and reversal agents.

Application of Propofol Target-Controlled Infusion for Optimized Hemodynamic Status in ESRD Patients Receiving Arteriovenous Access Surgery: A Randomized Controlled Trial.

Background and Objectives: End-stage renal disease (ESRD) is associated with increased anesthetic risks such as cardiovascular events resulting in higher perioperative mortality rates. This study investigated the perioperative and postoperative outcomes in ESRD patients receiving propofol target-controlled infusion with brachial plexus block during arteriovenous (AV) access surgery. Materials and Methods: We recruited fifty consecutive patients scheduled to receive AV access surgery. While all patients received general anesthesia combined with ultrasound-guided brachial plexus block, the patients were randomly assigned to one of two general anesthesia maintenance groups, with 23 receiving propofol target-controlled infusion (TCI) and 24 receiving sevoflurane inhalation. We measured perioperative mean arterial pressure (MAP), heart rate, and cardiac output and recorded postoperative pain status and adverse events in both groups. Results: ESRD patients receiving propofol TCI had significantly less reduction in blood pressure than those receiving sevoflurane inhalation (p < 0.05) during AV access surgery. Perioperative cardiac output and heart rate were similar in both groups. Both groups reported relatively low postoperative pain score and a low incidence of adverse events. Conclusions: Propofol TCI with brachial plexus block can be used as an effective anesthesia regimen for ESRD patients receiving AV access surgery. It can be used with less blood pressure fluctuation than inhalational anesthesia.

What Has Been the Impact of COVID-19 on Driving Digitalization, Innovation and Crisis Management of Higher Education and Quality Assurance?-A Taiwan Case Study in Alignment with the INQAAHE Virtual Review.

The impact of COVID-19 on higher education and quality assurance (QA) has already elicited global attention and discussion. QA agencies and networks quickly learned to adapt in order to carry out assessments, accreditations, recognitions, and reviews in a full virtual mode. These practices include using shared folders for virtual desk review, video conferencing platforms for interviews, and virtual site visits. In order to respond to the 2020 pandemic, The International Network for Quality Assurance Agencies in Higher Education (INQAAHE) swiftly adopted a virtual mode of the GGP review exercise for the GGP alignment applicants. The Higher Education Evaluation and Accreditation Council of Taiwan (HEEACT) was the first case that underwent a thorough virtual review process of GGP alignment during the 2020 pandemic. Therefore, this study aims to outline the impact of the pandemic in Taiwan higher education as well as provide the meta-analysis of the virtual review process of the INQAAHE GGP alignment by using HEEACT as a case study.

Interferon-ß suppresses inflammatory pain through activating µ-opioid receptor.

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-ß has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-ß in reducing mechanical allodynia caused by Complete Freund's Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-ß in naïve rats and the rats with CFA-induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-ß in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-ß antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-ß is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-ß at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-ß produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-ß injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/ßR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-ß is through µ-opioid receptors activation in spial cord.

An overview of biological applications and fundamentals of new inlet and vacuum ionization technologies.

RATIONALE: The developments of new ionization technologies based on processes previously unknown to mass spectrometry (MS) have gained significant momentum. Herein we address the importance of understanding these unique ionization processes, demonstrate the new capabilities currently unmet by other methods, and outline their considerable analytical potential. METHODS: The inlet and vacuum ionization methods of solvent-assisted ionization (SAI), matrix-assisted ionization (MAI), and laserspray ionization can be used with commercial and dedicated ion sources producing ions from atmospheric or vacuum conditions for analyses of a variety of materials including drugs, lipids, and proteins introduced from well plates, pipet tips and plate surfaces with and without a laser using solid or solvent matrices. Mass spectrometers from various vendors are employed. RESULTS: Results are presented highlighting strengths relative to ionization methods of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization. We demonstrate the utility of multi-ionization platforms encompassing MAI, SAI, and ESI and enabling detection of what otherwise is missed, especially when directly analyzing mixtures. Unmatched robustness is achieved with dedicated vacuum MAI sources with mechanical introduction of the sample to the sub-atmospheric pressure (vacuum MAI). Simplicity and use of a wide array of matrices are attained using a conduit (inlet ionization), preferably heated, with sample introduction from atmospheric pressure. Tissue, whole blood, urine (including mouse, chicken, and human origin), bacteria strains and chemical on-probe reactions are analyzed directly and, especially in the case of vacuum ionization, without concern of carryover or instrument contamination. CONCLUSIONS: Examples are provided highlighting the exceptional analytical capabilities associated with the novel ionization processes in MS that reduce operational complexity while increasing speed and robustness, achieving mass spectra with low background for improved sensitivity, suggesting the potential of this simple ionization technology to drive MS into areas currently underserved, such as clinical and medical applications.

Surgical resection significantly promotes the overall survival of patients with hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages. METHODS: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. RESULTS: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child-Pugh (C-P) class; (3) SR, hepatitis B virus (HBV) infection, and C-P class; and (4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages. CONCLUSIONS: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.

Near-IR Charge-Transfer Emission at 77 K and Density Functional Theory Modeling of Ruthenium(II)-Dipyrrinato Chromophores: High Phosphorescence Efficiency of the Emitting State Related to Spin-Orbit Coupling Mediation of Intensity from Numerous Low-Energy Singlet Excited States.

Efficient charge-transfer (CT) phosphorescence in the near-IR (NIR) spectral region is reported for four substituted Ru-(R-dipyrrinato) complexes, [Ru(bpy)2(R-dipy)](PF6), where bpy is 2,2'-bipyridine and the substituent R is phenyl (ph), 2,4,6-trimethylphenyl, 4-carboxyphenyl (HOOC-ph), or 4-pyridinyl. The experimentally determined phosphorescence efficiency, ιem(p) = kRAD(p)/(νem(p))3 (where kRAD(p) and νem(p) are the phosphorescence rate constant and the phosphorescence frequency, respectively), of the [Ru(bpy)2(R-dipy)]+ complexes was approximately double that of [Ru(bpy)(Am)4]2+ complexes (Am = ammine ligand) in the NIR region. Density functional theory (DFT) modeling indicated two strikingly different electronic configurations of the triplet emitting state (Te) in the two types of complexes. The Te of [Ru(bpy)2(R-dipy)]+ complexes shows a CT-type corresponding to the metal-to-ligand charge transfer (MLCT)-(Ru-(R-dipy)) and the ππ*-(R-dipy) moiety configurations, and the Te state in the [Ru(bpy)(Am)4]2+ complexes corresponds to an approximately MLCT excited state consisting of mostly MLCT-(Ru-bpy) with a minimal ππ*(bpy) contribution. DFT modeling also indicated that the low-energy singlet excited states in the Te geometry (Sn(T)) of the [Ru(bpy)2(ph-dipy)]+ complex consist of numerous CT-Sn(T)-type states of the Ru-dipy and Ru-bpy moieties, whereas the [Ru(bpy)(Am)4]2+ ions show quite simple MLCT-Sn(T)-type states of the Ru-bpy moiety. Based on experimental observations, DFT modeling, and the plain spin-orbit coupling (SOC) principle, we conclude that the remarkably high ιem(p) amplitudes of the [Ru(bpy)2(R-dipy)]+ complexes relative to those of [Ru(bpy)(Am)4]2+ complexes can be attributed to the relatively substantial contribution of intrinsic SOC-mediated intensity stealing from the numerous low-energy CT-type Sn(T) states.