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Abstract Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

The design and synthesis of a bifunctional catalyst to tackle environmental pollution caused by 2-chloroethyl ethyl sulfide (CEES) and phenolic compounds is meaningful. In this study, a new three-dimensional (3D) polyoxovanadate (POV)-based metal–organic framework, [Co(L)(V4O12)0.5(H2O)]·2H2O (1; L = N,N’-bis(3-methylpyridin-3-yl)-2,6-naphthalenediamide), was synthesized under hydrothermal conditions. 1 was characterized using single-crystal X-ray diffraction analysis, infrared spectroscopy, and powder X-ray diffraction. Structural analysis shows that the [V4O12]4– clusters and pairs of Co2+ cations are alternately connected to form a one-dimensional inorganic chain, eventually generating a 3D (4,4)-connected framework through the expansion of L, which exhibits a two fold interpenetration array. As a bifunctional catalyst, 1 exhibits satisfactory catalytic properties for the selective oxidation of 2-chloroethyl ethyl sulfide to the corresponding sulfoxide, with an effective conversion of > 99% and selectivity of 97%. Furthermore, 1 exhibits excellent photocatalytic degradation activity toward phenol, 2-chlorophenol, and m-cresol under visible light. The degradation efficiencies were above 92.6% for 140 min. The photocatalytic reaction kinetics, mechanisms of photodegradation, and recycling capability of phenol were also investigated in detail.

Abstract Background Iliopsoas plane block (IPB) is a novel analgesic technique for hip surgery that retains quadriceps strength. However, evidence from randomized controlled trial is remains unavailable. We hypothesized that IPB, as a motor-sparing analgesic technique, could match the femoral nerve block (FNB) in pain management and morphine consumption, providing an advantage for earlier functional training in patients underwent hip arthroplasty. Methods We recruited ninety patients with femoral neck fracture, femoral head necrosis or hip osteoarthritis who were scheduled for unilateral primary hip arthroplasty were recruited and received either IPB or FNB. Primary outcome was the pain score during hip flexion at 4 h after surgery. Secondary outcomes included quadriceps strength and pain scores upon arrival at post anesthesia care unit (PACU) and at 2, 4, 6, 24, 48 h after surgery, the first time out of bed, total opioids consumption, patient satisfaction, and complications. Results There was no significant difference in terms of pain score during hip flexion at 4 h after surgery between the IPB group and FNB group. The quadriceps strength of patients receiving IPB was superior to those receiving FNB upon arrival at PACU and at 2, 4, 6 and 24 h after surgery. The IPB group showed a shorter first time out of bed compared to the FNB group. However, there were no significant differences in terms of pain scores within 48 h after surgery, total opioids consumption, patient satisfaction and complications between the two groups. Conclusion IPB was not superior to FNB in terms of postoperative analgesia for hip arthroplasty. However, IPB could serve as an effective motor-sparing analgesic technique for hip arthroplasty, which would facilitate early recovery and rehabilitation. This makes IPB worth considering as an alternative to FNB. Trial registration The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055493; registration date: January 10, 2022; enrollment date: January 18, 2022; https://www.chictr.org.cn/searchprojEN.html ).

Organic polymer materials, as the most abundantly produced materials, possess a flammable nature, making them potential hazards to human casualties and property losses. Target polymer design is still hindered due to the lack of a scientific foundation. Herein, we present a robust, generalizable, yet intelligent polymer discovery framework, which synergizes diverse capabilities, including the in situ burning analyzer, virtual reaction generator, and material genomic model, to achieve results that surpass the sum of individual parts. Notably, the high-throughput analyzer created for the first time, grounded in multiple spectroscopic principles, enables in situ capturing of massive combustion intermediates; then, the created realistic apparatus transforming to the virtual reaction generator acquires exponentially more intermediate information; further, the proposed feature engineering tool, which embedded both polymer hierarchical structures and massive intermediate data, develops the generalizable genomic model with excellent universality (adapting over 20 kinds of polymers) and high accuracy (88.8%), succeeding discovering series of novel polymers. This emerging approach addresses the target polymer design for flame-retardant application and underscores a pivotal role in accelerating polymeric materials discovery.

Under hydrothermal conditions, a Keggin-type polyoxometalate-based metal–organic complex, H4{[Cu4(EDDP)2(H2O)5]1.5(SiW12O40)}∙7.5H2O (CuW-EDDP, H4EDDP = ethylene-diamine-N,N'-dipropionic acid), was synthesized by reacting Na10[A-α-SiW9O34]·18H2O and CuCl2·2H2O in the presence of H4EDDP ligands and characterized by powder and single-crystal X-ray diffraction, infrared spectroscopy, elemental analysis, and thermogravimetry. Interestingly, CuW-EDDP exhibited a three-dimensional structure with (4,6)-connected constructed from [SiW12O40]4− units and tetranuclear Cu complexes [Cu4(EDDP)2(H2O)5]. As an effective heterogeneous catalyst, CuW-EDDP exhibited excellent performance, good reusability, and structural stability in the selective oxidation of methyl phenyl sulfide with high conversion (100%) and selectivity (98%) within 30 min. Furthermore, the catalytic activity of CuW-EDDP in the oxidation of other sulfide derivatives was investigated.

One of the most important objectives for breeders is to develop high-yield cultivars. The increase in crop yield has met with bottlenecks after the first green revolution, and more recent efforts have been focusing on achieving high photosynthetic efficiency traits in order to enhance the yield. Leaf shape is a significant agronomic trait of upland cotton that affects plant and canopy architecture, yield, and other production attributes. The major leaf shape types, including normal, sub-okra, okra, and super-okra, with varying levels of lobe severity, are controlled by a multiple allelic series of the D-genome locus L-D1. To analyze the effects of L-D1 alleles on leaf morphology, photosynthetic related traits and yield of cotton, two sets of near isogenic lines (NILs) with different alleles were constructed in Lumianyan 22 (LMY22) and Lumianyan 28 (LMY28) backgrounds. The analysis of morphological parameters and the results of virus-induced gene silencing (VIGS) showed that the regulation of leaf shape by L-D1 alleles was similar to a gene-dosage effect. Compared with the normal leaf, deeper lobes of the sub-okra leaf improved plant canopy structure by decreasing the leaf area index (LAI) and increasing the light transmittance rate (LTR), and the mid-range LAI of sub-okra leaf also guaranteed the accumulation of cotton biomass. Although the chlorophyll content (SPAD) of sub-okra leaf was lower than those of the other two leaf shapes, the net photosynthetic rate (Pn) of sub-okra leaf was higher than those of okra leaf and normal leaf at most stages. Thus, the improvements in canopy structure, as well as photosynthetic and physiological characteristics, contributed to optimizing the light environment, thereby increasing the total biomass and yield in the lines with a sub-okra leaf shape. Our results suggest that the sub-okra leaf may have practical application in cultivating varieties, and could enhance sustainable and profitable cotton production.

Context Paclitaxel (PTX) leads to chemotherapy brain (chemo-brain) which is characterised by cognitive impairment. It has been reported that necroptosis is associated with cognitive impairment in some neurodegenerative diseases, but it is not clear whether it is related to the development of chemo-brain.Objective To investigate the role of necroptosis and related changes in PTX-induced cognitive impairment.Materials and methods C57bl/6n mice were randomly divided into five groups: control, vehicle, and different concentrations of PTX (6, 8, 10 mg/kg). Two additional groups received pre-treatment with Gdcl3 or PBS through Intracerebroventricular (ICV) injection before PTX-treatment. Cognitive function, necroptosis, synaptic plasticity and microglia polarisation were analysed.Results PTX (10 mg/kg) induced significant cognitive impairment, accompanied by changes in synaptic plasticity, including decreased density of PSD95 (0.65-fold), BDNF (0.44-fold) and dendritic spines (0.57-fold). PTX induced necroptosis of 53.41% (RIP3) and 61.91% (MLKL) in hippocampal neurons, with high expression of RIP3 (1.58-fold) compared with the control group. MLKL (1.87-fold) exhibited the same trend, reaching a peak on the 14th day. The increased expression of iNOS (1.63-fold) and inflammatory factors such as TNF-α (1.85-fold) and IL-β (1.89-fold) compared to the control group suggests that M1 polarisation of microglia is involved in the process of cognitive impairment. Pre-treatment with Gdcl3 effectively reduced the number of microglia (0.50-fold), inhibited the release of TNF-α (0.73-fold) and IL-β (0.56-fold), and improved cognitive impairment.Conclusion We established a stable animal model of PTX-induced cognitive impairment and explored the underlying pathophysiological mechanism. These findings can guide the future treatment of chemo-brain.

Anisotropic functional patterned surfaces have shown significant applications in microfluidics, biomedicine, and optoelectronics. Here, authors demonstrate a fast and mask-free etching method for accurate surface patterning by confined decomposition, enabling the efficient fabrication of complex patterns.

There will be generated some adverse conditions in the process of acquculture farming with the continuous improvement of the intensive degree of modern aquaculture, such as crowding stress, hypoxia, and malnutrition, which will easily lead to oxidative stress. Se is an effective antioxidant, participating and playing an important role in the antioxidant defense system of fish. This paper reviews the physiological functions of selenoproteins in resisting oxidative stress in aquatic animals, the mechanisms of different forms of Se in anti-oxidative stress in aquatic animals and the harmful effects of lower and higher levels of Se in aquaculture. To summarize the application and research progress of Se in oxidative stress in aquatic animals and provide scientific references for its application in anti-oxidative stress in aquaculture.

Abstract Background Hip fracture and surgery are associated with moderate to severe pain, which hampers early mobilization and extends the hospital stay. Femoral nerve block and fascia iliaca compartment block could provide effective postoperative pain relief. Unfortunately, they could weaken the strength of the quadriceps muscle and increase the risk of falls. Iliopsoas plane block (IPB) is a novel motor-sparing regional technique, which targets the sensory branches of the hip joint originating from the femoral nerve. However, the analgesic effect of IPB has not been confirmed yet. Case presentation In the present case series, IPB and lateral femoral cutaneous nerve block were implemented under the guidance of ultrasound for eight patients with hip fractures. The median (IQR) visual analog scale (VAS) score (0–10; 0: no pain, 10: worst pain) decreased from 1.5 (0.25–2) before IPB to 0 (0–0) 0.5h after IPB at rest. The median (IQR) VAS score decreased from 8 (7–8) before IPB to 2 (1–2) 0.5h after IPB during flexion of hip 30°. Pain score was no more than one at rest and three during flexion of the hip 30° within 48h after surgery. Furthermore, the MMT grades of quadriceps strength were no less than four after IPB. Conclusions Our case series firstly highlights that IPB might be an effective analgesic technique for hip fracture and surgery, while retaining motor function.

Abstract Background Pseudocohnilembus persalinus and Uronema marinum (Ciliophora, Scuticociliatia), as parasitic scuticociliatid ciliates, were isolated from Scophthalmus maximus and Takifugu rubripes, respectively, in our previous studies. These ciliates are morphologically very similar; hence, it is difficult to identify specific scuticociliate species using traditional classification methods for performing taxonomic research and disease control studies. Methods We annotated the mitochondrial genomes of these two scuticociliates on the basis of previous sequencing, including analyses of nucleotide composition, codon usage, Ka/Ks, and p-distance. We also compared the nucleotide and amino acid similarity of the mitochondrial genomes of P. persalinus, U. marinum, and other 12 related ciliates, and a phylogenetic tree was constructed using 16 common genes. We chose the nad4 and nad7 genes to design specific PCR primers for identification. Results P. persalinus and U. marinum were found to have a close evolutionary relationship. Although codon preferences were similar, differences were observed in the usage of codons such as CGA, CGC, and GTC. Both Ka/Ks and p-distance were less than 1. Except for yejR, ymf57, ymf67, and ymf75, the amino acid sequence similarity between P. persalinus and U. marinum was greater than 50%. Conclusions The mitochondrial genomes of P. persalinus and U. marinum were thoroughly compared to provide a reference for disease prevention and control. The specific PCR primers enabled us to identify P. persalinus and U. marinum rapidly and accurately at the molecular level, thus providing a basis for classification and identification. Graphic abstract

Abstract. Introduction:. Genital herpes is one of the most common sexually transmitted infections worldwide. Most genital herpes occur on the genitalia, perineum, buttocks, upper thighs, or perianal areas. However, there were reports of rare cases of genital herpes on urethral orifice. Herein, we report a case of a patient who was diagnosed with urethral orifice genital herpes, a place likely to be ignored. Case presentation:. A 53-year-old woman presented with vagina pruritus at first, with subsequent burning sensation around urethra. Mycostatin and mycospor were administered for the treatment of the pruritus. Then levofloxacin was prescribed. Finally, the patient was given treatment with acyclovir. Different from other cases, the investigation showed herpes simplex virus type 1 DNA positive and herpes simplex virus type 2 DNA negative by PCR. The patient was therefore diagnosed with genital herpes. Discussion:. Most genital herpes happen on the genitalia, perineum, buttocks, upper thighs, or perianal areas. Few cases have been reported that genital herpes occurred on urethral orifice till now. Conclusion:. If there is no typical symptoms that patient present with herpes simplex virus type 1 or 2 positive, urethral orifice genital herpes should be considered.

In this study, we aimed to study the effect of fluid shear stress on fibroblasts and BMSCs on plane and groove topographies. The results showed that 0.6-Hz stress had the greatest influence on the alignment, polarity, migration and adhesion of fibroblasts on plane by increasing the expression of reoriented actin and vinculin; whereas 1.0-Hz stress promoted differentiation of fibroblasts into myofibroblasts by increasing Col-I and α-SMA expression. Interestingly, under the given frequency stress, the groove structure strengthened the above characteristics of fibroblasts beyond adhesion, and promoted differentiation of BMSCs into myofibroblasts. The above results indicate that 0.6 Hz may improve the implant-tissue sealing, while 1.0-Hz stress probably causes the disordered fiber deposition around implants.

In recent years, with the increase in the frequency of residents’ trips, the problem of taking taxis in airports, train stations, and other transportation hubs has received wide attention, especially when we need to evacuate people in major emergencies such as epidemics, the traffic efficiency of these transportation hubs is critical. To improve the efficiency of passengers taking taxis at airports, the Hohhot Baita Airport in China is taken as an example, this paper studies the optimal queuing strategy of airport taxis under the condition of different numbers of pick-up points and drive lanes. based on the queuing theory, and the Monte Carlo simulation is adopted to obtain the average time spent by passengers to take taxis under different taxi-taking strategies, as well as the optimal number of taxi pick-up points and the optimal number of taxis in the boarding area under the condition of different numbers of lanes. The results show that the two-lane queuing model was significantly better than the single-lane queuing model, and the time optimization ratio exceeded 25%. However, the two independent lanes queuing mode could further reduce the average taxi-taking time by about 30%. The research results have an important reference value for the improvement of existing taxi lanes and the design of newly-constructed taxi lanes in airports, train stations, and other transportation hubs.

Background:The International Children's Continence Society defines overactive bladder (OAB) as a clinical syndrome characterized by urgency of urination usually accompanied by frequent urination and nocturia symptoms. This study aims to explore the correlation between overactive bladder (OAB) and allergy in children.Method:The clinical characteristics of 918 patients diagnosed with OAB from January 2020 to March 2021 were retrospectively analyzed. Risk factors for OAB were analyzed using logistic regression analysis, and the effect of desloratadine in the treatment of OAB was evaluated.Results:The incidence of allergic cough or allergic rhinitis in the mild OAB group was higher than the moderate–severe group. Urodynamics demonstrated that the proportion of patients with a sensitive bladder in the overactive detrusor group was significantly higher than the non-overactive detrusor group. The effective rate of treatment of OAB in patients complicated with allergies and taking desloratadine was 90.14%, which was significantly higher than in patients who were not taking desloratadine, and blood IgE level was a risk factor of ineffective treatment with desloratadine.Conclusion:OAB is correlated with allergies in children, and desloratadine can effectively improve OAB symptoms.

Globally, about two million people die from liver diseases every year. Liver transplantation is the only reliable therapy for severe end-stage liver disease, however, the shortage of organ donors is a huge limitation. Human hepatocytes derived liver progenitor-like cells (HepLPCs) have been reported as a novel source of liver cells for development of in vitro models, cell therapies, and tissue-engineering applications, but their functionality as transplantation donors is unclear. Here, a 3-dimensional (3D) co-culture system using HepLPCs and human umbilical vein endothelial cells (HUVECs) was developed. These HepLPC spheroids mimicked the cellular interactions and architecture of mature hepatocytes, as confirmed through ultrastructure morphology, gene expression profile and functional assays. HepLPCs encapsulated in alginate beads are able to mitigate liver injury in mice treated with carbon tetrachloride (CCL4), while alginate coating protects the cells from immune attack. We confirmed these phenomena due to HUVECs producing glial cell line-derived neurotrophic factor (GDNF) to promote HepLPCs maturation and enhance HepLPCs tight junction through MET phosphorylation. Our results display the efficacy and safety of the alginate microencapsulated spheroids in animal model with acute liver injury (ALF), which may suggest a new strategy for cell therapy.

By introducing a new “V”-like semirigid bis-imidazole-bis-amide ligand, 4,4’-bis(1H-imidazole-4-carboxamide)phenylmethane (L), into a reaction system containing Anderson-type polyoxoanions, three polyoxometalate-based metal–organic complexes (POMOCs) with different metal ions were successfully synthesized under solvothermal conditions. The as-prepared POMOCs [Zn2L2(H2O)4][Zn(H2O)2(TeMo6O24)]·9H2O (1), [Ni(H2O)6][Ni2L2(H2O)2[AlMo6(OH)6O18]2]·9H2O (2), and [Co(H2O)6][Co2L2(H2O)2[AlMo6(OH)6O18]2]·11.5H2O (3) show sandwich-like supramolecular structures. Complexes 2 and 3 are isostructural, having two [ML(H2O)2]2+ chains with [AlMo6(OH)6O18]3− polyoxoanions as pendants arranged in an interdigital mode to construct the sandwich-like architecture, whereas in complex 1 the anionic [Zn(H2O)2(TeMo6O24)]4− chain is sandwiched by two cationic [ZnL(H2O)2]2+ chains to generate the supramolecular structure. POMOCs 1–3 display excellent electrochemical sensing behavior for Cr(VI), Fe(III), BrO3−, and NO2− ions and efficient catalytic performance in sulfide oxidation. The effect of the central metal on the electrochemical sensing and sulfide oxidation performance and that of the special architecture of 1 on the detection ability are discussed.

As one of the most dangerous geological hazards in the world, debris flows can destroy trees and structures, break electrical, water, and gas lines, and disrupt bridges and roadways in a short period of time, threatening life and property. In particular, fast-moving large boulders carried by debris-induced destructive impact loading can strike objects without warning. To resist impact loading caused by rocks in debris, this paper proposed an innovative grid-type debris dam (or Sabo dam) design composed of symmetrical cross-sections of steel tubular flange beams and columns. This paper studied the dynamic performance of the tubular flange columns under impact loading by conducting lab tests and numerical simulations. Moreover, the dynamic response of the grid-type debris dam was simulated under various loading conditions. Comparing three different types of columns with similar configurations under the same loading condition, the tubular flange column proposed in this research exhibits better performance in overall strain, displacement, acceleration, and bending conditions. Furthermore, the results also prove that the proposed structure has excellent interoperability and energy absorption capabilities. When increasing the testing impact load, the failure modes of the dam change from dent at the impact point to local buckling and total failure of the structure, which indicates that the structure has superior performance under impact loading.

Background and Objectives. Tourniquet-induced ischemia/reperfusion (I/R) injury is a common clinical problem for patients receiving surgery. The objective of this study is to determine if oxycodone (Oxy) reduces skeletal muscle I/R damage induced by tourniquet placement and explores the underlying mechanisms. Method. Mice were randomly assigned to the sham, I/R, Oxy, and I/R with Oxy groups. Oxy was injected intraperitoneally 30 min before tourniquet placement. Morphological changes of the gastrocnemius muscle in these mice were assessed by hematoxylin-eosin (HE) staining and electron microscopy. Expression levels of TLR4, NF-κB, SIRT1, and PGC-1α in the skeletal muscles were detected by western blot. Blood TNF-α levels, gastrocnemius muscle contractile force, and ATP concentration were examined. Results. Compared with the I/R group, Oxy pretreatment attenuated skeletal muscle damage, decreased serum TNF-α levels, and inhibited the expression levels of TLR4/NF-κB in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1α levels were significantly reduced in gastrocnemius muscle after I/R. Oxy pretreatment recovered these protein expression levels. Conclusion. Tourniquet-induced acute limb I/R results in morphological and functional impairment in skeletal muscle. Pretreatment with Oxy attenuates skeletal muscle from acute I/R injury through inhibition of TLR4/NF-κB-dependent inflammatory response and protects SIRT1/PGC-1α-dependent mitochondrial function.

Objective To discuss the damage effect of Solitaire stent on tunica intima during thrombectomy, so as to evaluate the safety of thrombectomy. Methods Twelve healthy male New Zealand rabbits were randomly divided into 4 groups (3 rabbits in each group), including control group and 3 thrombectomy groups. Microcatheter was used instead of stent in control group. The other 3 groups underwent mimic thrombectomy for 1, 3 and 5 times in the same position, respectively. The procedure was performed at both sides of carotid artery of each rabbit. Immediately after operation, bilateral carotid arteries of each rabbit were removed, performed HE staining and examined the ultrastructure under microscope. Semi?quantitative analysis was used to evaluate the damage of carotid artery. Results During the model preparation, DSA showed the diameter of vascular wall was 2.10-2.90 mm, and there was no vascular spasm, bleeding, perforation or arterial dissection. Therefore, the model was successfully established. The difference of carotid artery damage among different groups was statistically significant (F = 119.108, P = 0.000). Compared with control group, the carotid artery damage of 3 thrombectomy groups was more serious (q = 3.136, P = 0.001; q = 7.463, P = 0.000; q = 10.682, P = 0.000). The carotid artery damage of the second and third thrombectomy group was more serious than the first group (q = 3.330, P = 0.000; q = 8.160, P = 0.000). The carotid artery damage of the third thrombectomy group was more serious than the second group (q = 4.830, P = 0.000). Optical microscope observation showed that with the increase of times of thrombectomy, carotid intimal injury was more extensive and intimal reaction was more severe. Scanning electron microscopy showed that with the increase of times of thrombectomy, the degree of carotid artery injury was increased. Conclusions Solitaire stent may injure tunica intima, and with the increase of times of thrombectomy, the damage to vascular wall will increase. DOI: 10.3969/j.issn.1672-6731.2017.11.008

Diabetic neuropathic pain (DNP) is a prevalent complication in diabetes patients. Neuronal inflammation and activation of Toll-like receptor 4 (TLR4) are involved in the occurrence of DNP. However, the underlying mechanisms remain unclear. Downregulation of gamma-aminobutyric acid B (GABAB) receptor contributes to the DNP. GABAB receptor interacts with NF-κB, a downstream signaling factor of TLR4, in a neuropathic pain induced by chemotherapy. In this study, we determined the role of TLR4/Myd88/NF-κB signaling pathways coupled to GABAB receptors in the generation of DNP. Intrathecal injection of baclofen (GABAB receptor agonist), LPS-RS ultrapure (TLR4 antagonist), MIP (MyD88 antagonist), or SN50 (NF-κB inhibitor) significantly increased paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWTL) in DNP rats, while intrathecal injection of saclofen (GABAB receptor blocker) decreased PWT and PWTL in DNP rats. The expression of TLR4, Myd88, NF-κBp65, and their downstream components IL-1 and TNF-α was significantly higher in the spinal cord tissue in DNP rats compared to control rats. Following inhibition of TLR4, Myd88, and NF-κB, the expression of IL-1 and TNF-α decreased. Activation of GABAB receptors downregulated the expression of TLR4, Myd88, NF-κBp65, IL-1, and TNF-α. Blockade of GABAB receptors significantly upregulated expression of TLR4, Myd88, NF-κBp65, IL-1, and TNF-α. These data suggest that activation of the TLR4/Myd88/NF-κB signaling pathway is involved in the occurrence of DNP in rats. Activation of GABAB receptor in the spinal cord may suppress the TLR4/Myd88/NF-κB signaling pathway and alleviate the DNP.

The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM) test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1β in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function.

Glycogen synthase kinases 3 (GSK3) α and β are expressed in the nervous system, and disruption of GSK3 signaling has been implicated in a wide range of neurodevelopmental and psychiatric disorders. Although several studies have established a role of GSK3 signaling in the nervous system, much less is known about isoform-specific functions. Here, we have examined the role of GSK3α and GSK3β in the developing neocortex by performing in utero electroporation with specific small interfering RNAs targeting each isoform. We found that depletion of either GSK3α or GSK3β commonly promoted the proliferation of neural progenitor cells in the ventricular zone, but at later stages, knocking down of each isoform resulted in distinct outcomes. In particular, the transformation of radial progenitors to intermediate progenitor cells was promoted in GSK3α-depleted cells, but markedly prevented in GSK3β-depleted cells. Moreover, knocking down of GSK3β but not GSK3α prevented the generation of upper-layer Cux1+ neurons. Consistent with the distinct outcomes, protein levels of c-Myc and β-catenin, well-known substrates of GSK3, were differentially affected by depletion of GSK3α and GSK3β. Together, these results suggest that GSK3α and GSK3β might play distinct roles in the genesis and differentiation of neuronal lineage cells during neocortex development by differential regulation of downstream signaling pathways.

Despite the wide range of available colorectal cancer (CRC) screening tests, less than 50% of cases are detected at early stages. However, the identification of differentially expressed proteins or novel protein biomarkers in CRC may have some utility and, ultimately, improve patient care and survival. Proteomics combined with mass spectroscopy and liquid chromatography are emerging as powerful tools that have led to the discovery of potential markers in cancer biomarker discovery in several types of cancers. This article describes a novel technology that uses isotopic reagents to tag selected proteins that show a consistent pattern of differential expression in CRC.

We have developed a Pt(COD)Cl2-catalyzed hydrative cyclization of 1,6-diynes leading to the formation of functionalized cyclohexenones in good yields.

Purpose: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) for the treatment of cutaneous lichen planus (LP). Methods: A total of 17 symptomatic LP lesions in 7 Chinese patients were assessed. ALA cream (10%) was applied topically to LP lesions for 3 h. The lesions were irradiated with a 635 nm diode laser at the dose level of 100 J/cm2. The treatment was repeated at two-week intervals. Clinical assessment was conducted before each treatment. Follow-up was performed once a month for up to six months. Results: Lesions showed significant improvement after one to four courses of treatments. Complete response was achieved in 13 lesions (five patients) and partial remission in four lesions (two patients). The complete response rate was 71%. There was no significant side effects except the feeling of pain that most patients could tolerate. Follow-up of five patients who achieved complete response showed no signs of recurrence. Conclusion: Topical ALA PDT is effective in the treatment of cutaneous LP.

Background. To explore the application of serum proteomic patterns for the preoperative detection of regional lymph node involvement of colorectal cancer (CRC). Methods. Serum samples were applied to immobilized metal affinity capture ProteinChip to generate mass spectra by Surface-Enhanced Laser Desorption/ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). Proteomic spectra of serum samples from 70 node-positive CRC patients and 75 age- and gender-matched node-negative CRC patients were employed as a training set, and a classification tree was generated by using Biomarker Pattern Software package. The validity of the classification tree was then challenged with a blind test set including another 65 CRC patients. Results. The software identified an average of 46 mass peaks/spectrum and 5 of the identified peaks at m/z 3,104, 3,781, 5,867, 7,970, and 9,290 were used to construct the classification tree. The classification tree separated effectively node-positive CRC patients from node-negative CRC patients, achieving a sensitivity of 94.29% and a specificity of 100.00%. The blind test challenged the model independently with a sensitivity of 91.43% a specificity of 96.67%. Conclusions. The results indicate that SELDI-TOF-MS can correctly distinguish node-positive CRC patients from node-negative ones and show great potential for preoperative screening for regional lymph node involvement of CRC.

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX‐induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long‐term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor‐interacting protein kinase (RIP3) and mixed lineage kinase domain‐like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin‐1 (Nec‐1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX‐induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX‐induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor‐α and IL‐β synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX‐induced polarization of spinal microglia leads to RIP3/MLKL‐regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]