Competition-Induced Macroscopic Superlubricity of Ionic Liquid Analogues by Hydroxyl Ligands Revealed by in Situ Raman.

High load-bearing capacity is one of the crucial indicators for liquid superlubricants to move toward practicality. However, some of the current emerging systems not only have low contact pressures but also are highly susceptible to further degradation due to water adsorption and even superlubricity failure. Herein, a novel choline chloride-based ionic liquid analogues (ILAs) of a superlubricant with triethanolamine (TEOA) as the H-bond donor is reported for the first time; it obtains an ultralow coefficient of friction (0.005) and high load-bearing capacity (360 MPa, more than 2 times that of similar systems) due to adsorption of a small amount of water (<5 wt %) from the air. In situ Raman combined with 1H NMR and FTIR techniques reveals that adsorbed water competes with the hydroxyl group of TEOA for coordination with Cl-, leading to the conversion of some strong H-bonds to weak H-bonds in ILAs; the localized strong H-bonds and weak H-bonds endow the ILAs with high load-bearing capacity and the formation of ultralow shear-resistance sliding interfaces, respectively, under the shear motion. This study proposes a strategy to modulate the interactions between liquid species using adsorbed water from air as a competing ligand, which provides new insights into the design of ILA-based macroscopic liquid superlubricants with a high load-bearing capacity.

Synthesis and photodynamic activity of novel thieno[3,2-b]thiophene fused BODIPYs with good bio-solubility and anti-aggregation effect.

To discover new photosensitizers with long wavelength UV-visible absorption, high efficiency, and low side effects for photodynamic therapy, here, a series of novel thieno[3,2-b]thiophene-fused BODIPY derivatives were designed, synthesized and characterized. These compounds had a distinct absorption band at 640-680 nm, fluorescence emission at 650-760 nm, and good solubility with anti-aggregation effects. These new compounds possessed obvious singlet oxygen generation ability and photodynamic anti-Eca-109 cancer cells activities in vitro. Among them, compound II4 could be well uptaked by Eca-109 cells, and result in the apoptosis after laser irradiation, and have outstanding photodynamic efficiency both in vitro and in vivo. Therefore, II4 could be considered as a potential photosensitizer drug candidate for PDT and photo-imaging.

Comparison of Outcomes of Facial Reanimation Between the Use of Cross-facial Nerve Graft and the Masseteric Nerve as the Donor Nerve for Reinnervation of Gracilis Muscle Flap Transfer.

BACKGROUND: In patients with facial paralysis, the free functional gracilis muscle transfer is preferred for facial reanimation. The choice of an adequate motor nerve to innervate the transplanted gracilis muscle is one of the procedure's key components. We present a comparative study between cross-facial nerve graft (CFNG) and masseteric nerve as donor nerves for reinnervated gracilis flap transfer in patients with complete facial paralysis. MATERLALS AND METHODS: Retrospective analysis was performed on all patients with complete facial paralysis who had a free functional gracilis muscle transfer for facial reanimation between January 2014 and December 2021. Only those who received gracilis transfer reinnervated by either CFNG or masseteric nerve were included in this study. The smile excursion and lip angle were measured for evaluating the outcomes postoperatively. RESULTS: The inclusion criteria were met by a total of 21 free functional gracilis muscle transfers, of which 11 were innervated by CFNG and 10 by the masseteric nerve. Both surgical procedures resulted in a highly considerable smile excursion of the reanimated side and postoperative improvement of static or dynamic lip angle. Masseteric nerve coaptation led to greater smile excursion and more significant improvement of dynamic lip angle than CFNG. CONCLUSIONS: For patients who have complete facial paralysis, face reanimation can be successfully accomplished by free gracilis transfer reinnervated by the CFNG or the masseteric nerve. In particular, the masseteric nerve is a reliable choice for dynamic smile reanimation.

Triboelectric Nanogenerators: State of the Art.

The triboelectric nanogenerator (TENG), as a novel energy harvesting technology, has garnered widespread attention. As a relatively young field in nanogenerator research, investigations into various aspects of the TENG are still ongoing. This review summarizes the development and dissemination of the fundamental principles of triboelectricity generation. It outlines the evolution of triboelectricity principles, ranging from the fabrication of the first TENG to the selection of triboelectric materials and the confirmation of the electron cloud overlapping model. Furthermore, recent advancements in TENG application scenarios are discussed from four perspectives, along with the research progress in performance optimization through three primary approaches, highlighting their respective strengths and limitations. Finally, the paper addresses the major challenges hindering the practical application and widespread adoption of TENGs, while also providing insights into future developments. With continued research on the TENG, it is expected that these challenges can be overcome, paving the way for its extensive utilization in various real-world scenarios.

Functional and aesthetic outcomes of abdominal full-thickness skin grafts in paediatric postburn digital and palmar flexion contractures.

The study aimed to assess the functional and aesthetic outcomes of abdominal full-thickness skin grafts (FTSGs) in paediatric postburn digital and palmar flexion contractures. The digital and palmar functions and aesthetics of 50 children who met the criteria were evaluated at pre-operation, the 3rd- and 12th-month post-operation, respectively. In the evaluation, the Vancouver Scar Scale (VSS), total active movement (TAM), and Jebsen-Taylor Hand Function Test (JHFT) were used. The contralateral, unaffected hand served as the criteria for functional recovery. The complications of donor sites were observed, and the take rate of skin grafts was calculated. The VSS scores at the 3rd and 12th months post-operation were lower than those before the operation. The TAM of each finger was improved at the 3rd and 12th months post-operation, compared with that before the operation. There was a significant difference in the time to complete the JHFT between the affected hand and the unaffected at the 3rd month post-operation, but no significant difference between them at the 12th month post-operation. The excellent and good take rate of the skin grafts was 90.00%.No donor site complications were observed. The abdominal FTSGs are effective in repairing paediatric digital and palmar scar contractures, with satisfying functional and aesthetic results, especially in large defects after scar release and resection.

Berberine ameliorates the neurological dysfunction of the gastric fundus by promoting calcium channels dependent release of ACh in STZ-induced diabetic rats.

Background: It has been reported diabetic gastroparesis is related to diabetic autonomic neuropathy of the gastrointestinal tract, and berberine (BBR) could ameliorate diabetic central and peripheral neuropathy. However, the influence of BBR on the function and motility of the gastric fundus nerve is unclear. Methods: A diabetic rat model was constructed, and HE staining was used to observe the morphological changes in the gastric fundus. The changes in cholinergic and nitrogen-related neurochemical indexes and the effects of BBR on them were measured using Elisa. The effects of BBR on the neural function and motility of gastric fundus were investigated by electric field stimulation (EFS) induced neurogenic response in vitro. Results: In the early stage of STZ-induced diabetic rats, the contractile response of gastric fundus induced by EFS was disorder, disturbance of contraction amplitude, and the cell bodies of neurons in the myenteric plexus of gastric fundus presented vacuolar lesions. Administration with BBR could improve the above symptoms. BBR further enhanced the contraction response in the presence of a NOS inhibitor or the case of inhibitory neurotransmitters removal. Interestingly, the activity of ACh could affect NO release directly and the enhancement of BBR on contractile response was canceled by calcium channel blockers completely. Conclusions: In the early stage of STZ-induced diabetic rats, the neurogenic contractile response disorder of the gastric fundus is mainly related to cholinergic and nitrergic nerve dysfunction. BBR promotes the release of ACh mainly by affecting the calcium channel to improve the neurological dysfunction of the gastric fundus.

Immunomodulatory functions of TRPM7 and its implications in autoimmune diseases.

An autoimmune disease is an inappropriate response to one's tissues due to a break in immune tolerance and exposure to self-antigens. It often leads to structural and functional damage to organs and systemic disorders. To date, there are no effective interventions to prevent the progression of autoimmune diseases. Hence, there is an urgent need for new treatment targets. TRPM7 is an enzyme-coupled, transient receptor ion channel of the subfamily M that plays a vital role in pathologic and physiologic conditions. While TRPM7 is constitutively activated under certain conditions, it can regulate cell migration, polarization, proliferation and cytokine secretion. However, a growing body of evidence highlights the critical role of TRPM7 in autoimmune diseases, including rheumatoid arthritis, multiple sclerosis and diabetes. Herein, we present (a) a review of the channel kinase properties of TRPM7 and its pharmacological properties, (b) discuss the role of TRPM7 in immune cells (neutrophils, macrophages, lymphocytes and mast cells) and its upstream immunoreactive substances, and (c) highlight TRPM7 as a potential therapeutic target for autoimmune diseases.

Modulating proteasome inhibitor tolerance in multiple myeloma: an alternative strategy to reverse inevitable resistance.

BACKGROUND: Resistance to proteasome inhibitors (PIs) is a major obstacle to the successful treatment of multiple myeloma (MM). Many mechanisms have been proposed for PI resistance; however, our mechanistic understanding of how PI resistance is inevitably acquired and reversed remains incomplete. METHODS: MM patients after bortezomib relapse, MM cell lines and mouse models were used to generate matched resistant and reversed cells. RNA sequencing and bioinformatics analyses were employed to assess dysregulated epigenetic regulators. In vitro and in vivo procedures were used to characterise PI-tolerant cells and therapeutic efficacy. RESULTS: Upon PI treatment, MM cells enter a slow-cycling and reversible drug-tolerant state. This reversible phenotype is associated with epigenetic plasticity, which involves tolerance rather than persistence in patients with relapsed MM. Combination treatment with histone deacetylase inhibitors and high-dosage intermittent therapy, as opposed to sustained PI monotherapy, can be more effective in treating MM by preventing the emergence of PI-tolerant cells. The therapeutic basis is the reversal of dysregulated epigenetic regulators in MM patients. CONCLUSIONS: We propose an alternative non-mutational PI resistance mechanism that explains why PI relapse is inevitable and why patients regain sensitivity after a 'drug holiday'. Our study also suggests strategies for epigenetic elimination of drug-tolerant cells.

Facial Animation With Free Functional Gracilis Transfer Innervated by the Cross-Facial Nerve Graft.

BACKGROUND: The treatment of long-standing facial paralysis has always been a challenge for plastic surgery. The purpose of this study was to demonstrate that the free functional gracilis transfer innervated by the cross-facial nerve graft (CFNG) is still an ideal option, even though there are many new surgical options available. METHODS: A retrospective survey was made on 12 patients who received free functional gracilis transfer innervated by the CFNG. A modified version of the House-Brackmann scale was used to evaluate the movement of the corners of mouth after surgery. Patients were also asked about their satisfaction with the operation. In addition, an objective test was performed to assess the postoperative angle improvement by measuring the angle formed between the horizontal line of both corners of the lips and the vertical midline. RESULTS: All grafts survived well. No severe complication occurred. Three patients received further surgical operations for aesthetic reasons. The movement of the corners of mouth was classified as excellent in 8 cases, good in three cases, and fair in one cases. The static angle and dynamic angle of postoperation improved and the range of dynamic angle improvement was larger than that of static angle. CONCLUSION: Free functional gracilis transfer innervated by the CFNG is an ideal technique for facial paralysis. It can effectively improve the facial dynamic of the affected side.

Vanadium compounds induced damage of human umbilical vein endothelial cells and the protective effect of berberine.

This study was conducted to investigate the damage caused by vanadium compounds and to explore the protective effects of berberine (BBR) in human umbilical vein endothelial cells (HUVECs). BBR is a biologically active small molecule found in Coptis rhizome, a remedy used in traditional Chinese medicine to treat diabetes. BBR has also been shown to lower blood glucose in diabetic patients. MTT assay was performed to observe the influence of bis(acetylacetonato)-oxidovanadium [VO(acac)2] or sodium metavanadate (NaVO3) and BBR on viability of HUVECs. The monolayer permeability of the HUVECs was assessed by measuring the transendothelial electrical resistance (TER). The endothelial nitric oxide synthase (eNOS) activity was detected by ELISA. Flow cytometry was performed to detect the generation of reactive oxygen species (ROS). The results showed that the viability of HUVECs was decreased by treatment with vanadium compounds 50-400 µM in a concentration-dependent manner, while 0.01-1 µM BBR effectively protected HUVECs from the inhibitory effects of vanadium compounds on cell viability. Also 100 and 200 µM VO(acac)2 induced high permeability and decreased eNOS activity in HUVECs. While 0.01-1 µM BBR showed no improvement in the permeability, and failed to reverse the VO(acac)2-induced changes of eNOS activity, but BBR treatment increased the eNOS activity in control cells. The addition of 200 µM VO(acac)2 significantly induced ROS generation in HUVECs, while 0.01 or 0.1 µM BBR reversed the change of ROS. In summary, BBR has protective effects in HUVECs damage induced by vanadium compounds, which is not mediated by eNOS, but related to reduced intracellular ROS.

Stress-Induced Mucus Secretion and Its Composition by a Combination of Proteomics and Metabolomics of the Jellyfish Aurelia coerulea.

BACKGROUND: Jellyfish respond quickly to external stress that stimulates mucus secretion as a defense. Neither the composition of secreted mucus nor the process of secretion are well understood. METHODS: Aurelia coerulea jellyfish were stimulated by removing them from environmental seawater. Secreted mucus and tissue samples were then collected within 60 min, and analyzed by a combination of proteomics and metabolomics using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), respectively. RESULTS: Two phases of sample collection displayed a quick decrease in volume, followed by a gradual increase. A total of 2421 and 1208 proteins were identified in tissue homogenate and secreted mucus, respectively. Gene Ontology (GO) analysis showed that the mucus-enriched proteins are mainly located in extracellular or membrane-associated regions, while the tissue-enriched proteins are distributed throughout intracellular compartments. Tryptamine, among 16 different metabolites, increased with the largest-fold change value of 7.8 in mucus, which is consistent with its involvement in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway 'tryptophan metabolism'. We identified 11 metalloproteinases, four serpins, three superoxide dismutases and three complements, and their presence was speculated to be related to self-protective defense. CONCLUSIONS: Our results provide a composition profile of proteins and metabolites in stress-induced mucus and tissue homogenate of A. coerulea. This provides insight for the ongoing endeavors to discover novel bioactive compounds. The large increase of tryptamine in mucus may indicate a strong stress response when jellyfish were taken out of seawater and the active self-protective components such as enzymes, serpins and complements potentially play a key role in innate immunity of jellyfish.

Pharmacological evaluation of orexin receptor antagonists in preclinical animal models of pain.

Orexin signaling, known to modulate arousal and vigilance, is also involved in nociception as orexin neurons project to regions of the brain and spinal cord involved in pain processing, and the administration of orexin peptides can alter pain response in a wide range of preclinical models. Pharmacological treatment with the potent, selective and structurally distinct dual orexin receptor antagonists (ORAs) DORA-12 and DORA-2 significantly reduced pain responses during both phases I and II of the mouse formalin pain model and significantly reversed hyperalgesia in the rat complete Freund's adjuvant pain model, respectively. Significant antinociceptive effects of DORA-12 in the formalin model were also observed in orexin 1 receptor (OX1R) knockout mice, but not orexin 2 receptor (OX2R) or OX1R/OX2R double knockout mice. Mechanical hypersensitivity was significantly reduced with a series of structurally distinct, potent and highly selective ORAs (DORA-2, DORA-12 and DORA-22) in the rat spinal nerve ligation (SNL) injury model of neuropathic pain. Selective pharmacological targeting of OX2R with 2-SORA-7 also reduced pain responses in acute inflammatory (complete Freund's adjuvant) and neuropathic (SNL) rat pain models. Performance on the rotarod test of psychomotor performance and baseline thermal sensitivity were not affected in OX1R/OX2R knockout mice or ORA-treated mice, indicating that the observed pain-reducing effects were not due to sedation or motor deficits. These findings indicate that ORAs have pain-reducing effects across a number of acute and chronic neuropathic preclinical mouse and rat pain models. Further studies on the potential pain-relieving effects of orexin receptor antagonism are warranted.

Evolutionary and ontogenetic changes in RNA editing in human, chimpanzee, and macaque brains.

Adenosine-to-inosine (A-to-I) substitutions are the most common type of RNA editing in mammals. A-to-I RNA editing is particularly widespread in the brain and is known to play important roles in neuronal functions. In this study we investigated RNA-editing changes during human brain development and maturation, as well as evolutionary conservation of RNA-editing patterns across primates. We used high-throughput transcriptome sequencing (RNA-seq) to quantify the RNA-editing levels and assess ontogenetic dynamics of RNA editing at more than 8000 previously annotated exonic A-to-I RNA-editing sites in two brain regions--prefrontal cortex and cerebellum--of humans, chimpanzees, and rhesus macaques. We observed substantial conservation of RNA-editing levels between the brain regions, as well as among the three primate species. Evolutionary changes in RNA editing were nonetheless evident, with 40% of the annotated editing sites studied showing divergent editing levels among the three species and 16.5% of sites displaying statistically significant human-specific editing patterns. Across lifespan, we observed an increase of the RNA-editing level with advanced age in both brain regions of all three primate species.

Counterfactual comparison modulates fairness consideration in the mini-ultimatum game: an event-related potentials study.

Existing literature on the mini-ultimatum game indicates that counterfactual comparison between chosen and unchosen alternatives is of great importance for individual's fairness consideration. However, it is still unclear how counterfactual comparison influences the electrophysiological responses to unfair chosen offers. In conjunction with event-related potentials' (ERPs) technique, the current study aimed to explore the issue by employing a modified version of the mini-ultimatum game where a fixed set of two alternatives (unfair offer vs. fair alternative, unfair vs. hyperfair alternative, unfair offer vs. hyperunfair alternative) was presented before the chosen offer. The behavioral results showed that participants were more likely to accept unfair chosen offers when the unchosen alternative was hyperunfair than when the unchosen alternative was fair or hyperfair. The ERPs results showed that the feedback-related negativity (FRN) elicited by unfair chosen offers was insensitive to the type of unchosen alternative when correcting for possible overlap with other components. In contrast, unfair chosen offers elicited larger P300 amplitudes when the unchosen alternative was hyperunfair than when the unchosen alternative was fair or hyperfair. These findings suggest that counterfactual comparison may take effect at later stages of fairness consideration as reflected by the P300.

MicroRNA expression and regulation in human, chimpanzee, and macaque brains.

Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA) in the regulation of gene expression divergence among adult humans, chimpanzees, and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using a combination of high-throughput sequencing, miRNA microarrays, and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2%-4% of mRNA and 4%-6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA-driven regulation on the human evolutionary lineage, was further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions.

Epicardial Adipose Tissue and Left Ventricular Systolic Function in Rheumatoid Arthritis Assessed by Two-Dimensional Speckle Tracking Echocardiography.

Introduction Epicardial adipose tissue (EAT) is an emerging cardiovascular biomarker. Subclinical left ventricular (LV) systolic dysfunction is common in rheumatoid arthritis (RA). The aim of this study was to assess LV systolic function using two-dimensional speckle tracking echocardiography (2D-STE) and investigate its association with EAT in RA patients without clinical cardiovascular disease (CVD). Methods 60 RA patients without manifestations of CVD and 60 age- and gender-matched healthy controls have been recruited for the study. We assessed LV systolic function and EAT in all subjects using conventional echocardiography and 2D-STE. EAT was measured as the relative echo-free region between the free wall of the right ventricle and the visceral layer of the pericardium at end-systole. Results Global longitudinal strain (GLS) was decreased and EAT was increased in the RA group compared to the control group. GLS was reduced as EAT increased in RA patients (r=-0.273, P=0.035). After adjusting for confounders, multivariate linear regression analysis revealed a weakened correlation between EAT and GLS.Age and disease activity scores28 were independent factors influencing GLS in RA. Conclusion RA patients have significantly thickened EAT compared with controls. 2D-STE can detect early LV myocardial systolic dysfunction in RA, as shown by lower GLS. Accumulation of EAT is associated with lower GLS, but older age and higher disease activity may play a greater role in LV myocardial systolic dysfunction in RA.

Highly Concentrated Electrolyte Superlubricants Enhanced by Interfacial Water Competition Around Chemically Active MgO Additives.

The low concentration of water-based lubricants and the high chemical inertness of the additives involved are often regarded as basic norms in the design of liquid lubricants. Herein, a novel liquid superlubricant of an aqueous solution containing a relatively high concentration of salt, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), is reported for the first time, and the superlubricity stability and load-bearing capacity of the optimized system (MgO0.10/LiTFSI10) are effectively strengthened by the addition of only trace (0.10 wt %) water-chemically active MgO additives. It demonstrates higher applicable loads, lower COF (∼0.004), and stability relative to the base solution. Only a trace amount of MgO additive is needed for the superlubricity, which makes up for the cost and environmental deficiencies of LiTFSI10. The weak interaction region between free water and the outer-layer water of Li+ hydration shells becomes a possible ultralow shear resistance sliding interface; the Mg(OH)2 layer, generated by the reaction of MgO with water, further creates additional weakly interacting interfaces, leading to the formation of an asymmetric contact between the clusters/particles within the hydrodynamic film by moderating the competition between interfacial water and free water, thus achieving high load-bearing macroscopic superlubricity. This study deepens the contribution of electrolyte concentration to ionic hydration and superlubricity due to the low shear slip layer formed by interfacial water competition with water-activated solid additives, providing new insights into the next generation of high load-bearing water-based liquid superlubricity systems.

[Immune Reconstitution after BTKi Treatment in Chronic Lymphocytic Leukemia].

OBJECTIVE: To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia (CLL). METHODS: The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively. RESULTS: The median age of 59 CLL patients was 60.5(36-78). After one year of BTKi treatment, the CLL clones (CD5 +/CD19 +) of 51 cases (86.4%) were significantly reduced, in which the number of cloned-B cells decreased significantly from (46±6.1)×109/L to (2.3±0.4)×109/L (P =0.0013). But there was no significant change in the number of non-cloned B cells (CD19 + minus CD5 +/CD19 +). After BTKi treatment, IgA increased significantly from (0.75±0.09)g/L to (1.31±0.1)g/L (P <0.001), while IgG and IgM decreased from (8.1±0.2)g/L and (0.52±0.6)g/L to (7.1±0.1)g/L and (0.47±0.1)g/L, respectively (P <0.001, P =0.002). BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients, which manifested as both a decrease in total number of T cells from (2.1±0.1)×109/L to (1.6±0.4)×109/L and NK/T cells from (0.11±0.1)×109/L to (0.07±0.01)×109/L (P =0.042, P =0.038), both an increase in number of CD4 + cells from (0.15±6.1)×109/L to (0.19±0.4)×109/L and CD8 + cells from (0.27±0.01)×109/L to (0.41±0.08)×109/L (both P <0.001). BTKi treatment also up-regulated the expression of interleukin (IL)-2 while down-regulated IL-4 and interferon (IFN)-γ. However, the expression of IL-6, IL-10, and tumor necrosis factor (TNF)-α did not change significantly. BTKi treatment could also restored the diversity of TCR and BCR in CLL patients, especially obviously in those patients with complete remission (CR) than those with partial remission (PR). Before and after BTKi treatment, Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001 (P <0.001), while in patients with PR was 0.01±0.03 and 0.05±0.02 (P >0.05), respectively. Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15 (P <0.001), while in patients with PR was 0.15±0.009 and 0.23±0.18 (P <0.05), respectively. CONCLUSIONS: BTKi treatment can shrink the clone size in CLL patients, promote the expression of IgA, increase the number of functional T cells, and regulate the secretion of cytokines such as IL-2, IL-4, and IFN-γ. BTKi also promote the recovery of diversity of TCR and BCR. BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Synthesis and Evaluation of Novel meso-Tetraphenyltetrabenzoporphyrins for Photodynamic Therapy.

To discover effective photosensitizers for photodynamic therapy (PDT), a series of new meso-tetraphenyltetrabenzoporphyrin (m-Ph4TBP) derivatives were designed, prepared, and characterized. All m-Ph4TBPs own two characteristic absorption bands in the range of 450-500 and 600-700 nm and have the ability to generate singlet oxygen upon photoexcitation. Most of the m-Ph4TBPs demonstrated high photoactivity, among which compounds I4, I6, I12, and I13 induced apoptosis and also exhibited excellent photodynamic activities in vivo. Nonetheless, the liver organs of the I4 and I6-PDT groups showed clear calcifications, whereas the liver tissues of the other PDT groups showed no calcification. It was indicated that compared to phenolic m-Ph4TBPs, glycol m-Ph4TBPs exhibited superior biological safety in mice. According to comprehensive evaluations, m-Ph4TBP I12 displayed excellent photodynamic antitumor efficacy and biological safety and can be regarded as a promising antitumor drug candidate.