Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management.

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.

Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

Constructing a Low-Cost Si-NSs@C/NG Composite by a Ball Milling-Catalytic Pyrolysis Method for Lithium Storage.

Silicon-based composites are promising candidates as the next-generation anode materials for high-performance lithium-ion batteries (LIBs) due to their high theoretical specific capacity, abundant reserves, and reliable security. However, expensive raw materials and complicated preparation processes give silicon carbon anode a high price and poor batch stability, which become a stumbling block to its large-scale practical application. In this work, a novel ball milling-catalytic pyrolysis method is developed to fabricate a silicon nanosheet@amorphous carbon/N-doped graphene (Si-NSs@C/NG) composite with cheap high-purity micron-size silica powder and melamine as raw materials. Through systematic characterizations such as XRD, Raman, SEM, TEM and XPS, the formation process of NG and a Si-NSs@C/NG composite is graphically demonstrated. Si-NSs@C is uniformly intercalated between NG nanosheets, and these two kinds of two-dimensional (2D) materials are combined in a surface-to-surface manner, which immensely buffers the stress changes caused by volume expansion and contraction of Si-NSs. Attributed to the excellent electrical conductivity of graphene layer and the coating layer, the initial reversible specific capacity of Si-NSs@C/NG is 807.9 mAh g-1 at 200 mA g-1, with a capacity retention rate of 81% in 120 cycles, exhibiting great potential for application as an anode material for LIBs. More importantly, the simple and effective process and cheap precursors could greatly reduce the production cost and promote the commercialization of silicon/carbon composites.

Modulating the Graphitic Domains and Pore Structure of Corncob-Derived Hard Carbons by Pyrolysis to Improve Sodium Storage.

Biomass-derived hard carbon materials are considered as the most promising anode materials for sodium-ion batteries (SIBs) due to their abundant sources, environmental friendliness, and excellent electrochemical performance. Although much research exists on the effect of pyrolysis temperature on the microstructure of hard carbon materials, there are few reports that focus on the development of pore structure during the pyrolysis process. In this study, corncob is used as the raw material to synthesize hard carbon at a pyrolysis temperature of 1000~1600 °C, and their interrelationationship between pyrolysis temperature, microstructure and sodium storage properties are systematically studied. With the pyrolysis temperature increasing from 1000 °C to 1400 °C, the number of graphite microcrystal layers increases, the long-range order degree rises, and the pore structure shows a larger size and wide distribution. The specific capacity, the initial coulomb efficiency, and the rate performance of hard carbon materials improve simultaneously. However, as the pyrolysis temperature rises further to 1600 °C, the graphite-like layer begins to curl, and the number of graphite microcrystal layers reduces. In return, the electrochemical performance of the hard carbon material decreases. This model of pyrolysis temperatures-microstructure-sodium storage properties will provide a theoretical basis for the research and application of biomass hard carbon materials in SIBs.

Activation of Different Heterodimers of TLR2 Distinctly Mediates Pain and Itch.

Toll-like receptors (TLRs) have been implicated in pain and itch regulation. TLR2, a TLR family member that detects microbial membrane components, has been implicated in pathologic pain. However, the role of TLR2 in pruritic and nociceptive responses has not been thoroughly investigated. In this study, we found that TLR2 was expressed in mouse dorsal root ganglia (DRG) and trigeminal ganglia (TG) neurons. Itch and pain behaviors, including histamine-dependent and histamine-independent acute itching, acetone/diethyl ether/water and 2,4-dinitrofluorobenzene-induced chronic itching and inflammatory pain, were largely attenuated in TLR2 knockout (KO) mice. The TLR2 agonist Pam3CSK4, which targets TLR2/1 heterodimers, evoked pain and itch behavior, whereas lipoteichoic acid (LTA) and zymosan, which recognize TLR2/6 heterodimers, produced only pain response. The TLR2 agonist-induced nociceptive and pruritic behaviors were largely diminished in transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) KO mice. Finally, Pam3Csk4 and zymosan increased the [Ca2+]i in DRG neurons from wild-type mice. However, the enhancement of [Ca2+]i was largely inhibited in the DRG neurons from TRPV1 and TRPA1 KO mice. Our results demonstrate that TLR2 is involved in different itch and pain behaviors through activating TLR1/TLR2 or TLR6/TLR2 heterodimers via TRPV1 and TRPA1 channels.

The In-Situ Synthesis of a 3D SnS/N-Doped Graphene Composite with Enhanced Electrochemical Performance as a Low-Cost Anode Material in Sodium Ion Batteries.

SnS/N-doped graphene (SnS/NG) composites are promising anode materials for sodium ion batteries. Generally, SnS is synthesized from SnCl2·2H2O. However, SnCl2·2H2O is not suitable for large-scale production due to its high price. Compared with SnCl2·2H2O, SnCl4·5H2O has a lower price, more stable chemical properties and better water solubility. Until now, there have been no related reports on the synthesis of SnS from SnCl4·5H2O. In this work, the fabrication of SnS/NG in a facile, two-step process, which combines a hot water bath and thermal annealing and uses SnCl4·5H2O as a precursor, is described. The mechanism of phase transformation in the direct synthesis of SnS from Sn4+ is also discussed in detail. Applying our methodology, SnS nanoparticles were grown in-situ on graphene sheets and wrapped by N-doped graphene sheets to form a 3D SnS/NG composite. With 35.35% content of graphene in the SnS/NG composite, the reversible specific capacity remained at 417.8 mAh/g at 1000 mA/g after 100 cycles, exhibiting a high specific capacity and good cycling stability. In addition, the composite also had an excellent rate performance, with a specific capacity of 366.9 mAh/g obtained even at 5000 mA/g. Meanwhile, the fast sodium storage kinetics of SnS/NG were also analyzed, providing some theoretical support for further study.

Risk factors and negative consequences of patient's delay for penile carcinoma.

BACKGROUND: Delayed first medical consultation (patient's delay) is quite common in cases of penile carcinoma (PC), but its reasons and impacts remain unclear. We conducted this study to ascertain risk factors resulting in delayed treatment seeking and evaluate its influence on prognosis. METHODS: From 2004 to 2010 at 4 centers, 254 patients were enrolled into this study from 262 consecutive PC cases. Patients' sexual performance was investigated using the International Index of Erectile Function (IIEF)-15 at the sixth-month end after treatment. Data for prognostic analyses was obtained via a 5-year follow-up. RESULTS: A multivariate model ascertained 4 risk factors (single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms) and 1 protective factor (history of condyloma) significantly associated with patient's delay. Delay >3 months led to significant risks for adverse clinical characteristics, low penis-sparing rate, and poor sexual function restoration. Although patient's delay was not found to impact on postoperative relapses and 5-year overall survival (OS), patients with delay >6 months had significantly inferior 2-year OS. CONCLUSIONS: Single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms are significant risk factors of PC associated with patient's delay. Delay >3 months will lead to significantly inferior clinical consequences. Minimizing patient's delay is the key to avoid amputation and retain superior sexual potency. Improving patient education on initial symptoms of PC is necessary in men of >40 years old.

Extracellular signal-regulated kinase (ERK) activation is required for itch sensation in the spinal cord.

BACKGROUND: Itch, chronic itch in particular, can have a significant negative impact on an individual's quality of life. However, the molecular mechanisms underlying itch processing in the central nervous system remain largely unknown. RESULTS: We report here that activation of ERK signaling in the spinal cord is required for itch sensation. ERK activation, as revealed by anti-phosphorylated ERK1/2 immunostaining, is observed in the spinal dorsal horn of mice treated with intradermal injections of histamine and compound 48/80 but not chloroquine or SLIGRL-NH2, indicating that ERK activation only occurs in histamine-dependent acute itch. In addition, ERK activation is also observed in 2, 4-dinitrofluorobenzene (DNFB)-induced itch. Consistently, intrathecal administration of the ERK phosphorylation inhibitor U0126 dramatically reduces the scratching behaviors induced by histamine and DNFB, but not by chloroquine. Furthermore, administration of the histamine receptor H1 antagonist chlorpheniramine decreases the scratching behaviors and ERK activation induced by histamine, but has no effect on DNFB-induced itch responses. Finally, the patch-clamp recording shows that in histamine-, chloroquine- and DNFB-treated mice the spontaneous excitatory postsynaptic current (sEPSC) of dorsal horn neurons is increased, and the decrease of action potential threshold is largely prevented by bathing of U0126 in histamine- and DNFB-treated mice but not those treated with chloroquine. CONCLUSION: Our results demonstrate a critical role for ERK activation in itch sensation at the spinal level.

Glans preservation contributes to postoperative restoration of male sexual function: a multicenter clinical study of glans preserving surgery.

PURPOSE: We evaluated whether glans preserving surgery would be more helpful for patients to regain satisfactory sexual competency postoperatively than conventional partial amputation. MATERIALS AND METHODS: From 2004 to 2012 at 4 centers a total of 135 men treated with glans preserving surgery and 36 treated with partial amputation were selected for evaluation from a total of 273 consecutive patients with penile cancer. Subjective evaluation for patient sexual performance was investigated using the IIEF-15. Objective evaluation was done using the audiovisual sexual stimulation test with the RigiScan® Plus. The degree of satisfaction with penile appearance, and patient confidence and partner acceptability for intercourse were evaluated by 5-point scales. RESULTS: Patients treated with glans preserving surgery had better performance in 4 IIEF-15 domains (erectile function, orgasmic function, intercourse satisfaction and overall satisfaction) and 1 RigiScan parameter (tip rigidity) (each p <0.01). They also had significantly higher appearance satisfaction (64.4% vs 13.9%) and intercourse confidence (55.6% vs 5.6%) than men who underwent partial amputation. Sexual partners in the glans preserving group also showed significantly higher appearance satisfaction (51.1% vs 5.6%) and intercourse acceptability (37.8% vs 16.7%) than in the partial amputation group. CONCLUSIONS: Glans preserving surgery effectively preserves the functional anatomy and cosmetic appearance of the glans penis. Glans preservation contributes to minimizing postoperative erectile dysfunction and negative psychological impediments, and promotes return to satisfactory sexual performance. Patients treated with glans preservation have more advantages in obtaining sexual acceptance from their partners than those who undergo amputation.

Prognostic significance of phosphorylated signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3 expression in human cutaneous melanoma.

Cutaneous malignant melanoma is one of the most common and aggressive forms of human cancers and has a poor prognosis. Activation of signal transducer and activator of transcription 3 (STAT3) has been found in several human cancers and is thought to correlate aggressive disease and poor response. In this study, we investigated the clinical role of STAT3 and its natural inhibitor, suppressor of cytokine signaling 3 (SOCS3), in human cutaneous melanoma development and progression. Immunohistochemical analysis of pSTAT3, SOCS3, matrix metalloproteinase (MMP)-2, and MMP-9 expression was performed on 90 primary melanomas and 43 common melanocytic nevi specimens. The expression of STAT3 mRNA was further detected by in-situ hybridization in the same cohort of patients. The association of STAT3 mRNA, pSTAT3, and SOCS3 protein expression with clinicopathological parameters and patient survival was analyzed. Altered expression of STAT3 mRNA, pSTAT3, and SOCS3 protein was observed in melanoma specimens, compared with benign melanocytic nevi. High expression of pSTAT3 was correlated to large tumor diameter, depth of tumor invasion, tumor lymph node metastasis, MMP-2 and MMP-9 expression, and poor patient survival. Decreased expression of SOCS3 was correlated to depth of tumor invasion, tumor lymph node metastasis, the expression of MMP-2, MMP-9, and pSTAT3, and poor patient survival. Moreover, the expression of pSTAT3 was conversely correlated to SOCS3 expression in melanoma. Our results indicate that deregulated expression of pSTAT3 and SOCS3 might possess potential roles in the development and progression of human cutaneous melanoma.