LKB1 is physiologically required for sleep from Drosophila melanogaster to the Mus musculus.

Liver Kinase B1 (LKB1) is known as a master kinase for 14 kinases related to the adenosine monophosphate-activated protein kinase. Two of them salt inducible kinase 3 and adenosine monophosphate-activated protein kinase α have previously been implicated in sleep regulation. We generated loss-of-function mutants for Lkb1 in both Drosophila and mice. Sleep, but not circadian rhythms, was reduced in Lkb1-mutant flies and in flies with neuronal deletion of Lkb1. Genetic interactions between Lkb1 and threonine to alanine mutation at residue 184 of adenosine monophosphate-activated protein kinase in Drosophila sleep or those between Lkb1 and Threonine to Glutamic Acid mutation at residue 196 of salt inducible kinase 3 in Drosophila viability have been observed. Sleep was reduced in mice after virally mediated reduction of Lkb1 in the brain. Electroencephalography analysis showed that nonrapid eye movement sleep and sleep need were both reduced in Lkb1-mutant mice. These results indicate that liver kinase B1 plays a physiological role in sleep regulation conserved from flies to mice.

Effectiveness of photodynamic therapy with 5-aminolevulinic acid for Bowenoid papulosis: A retrospective study with long-term follow-up.

BACKGROUND: Bowenoid papulosis (BP) is a rare infectious skin disease that occurs in sexually active young people. BP is associated with human papillomavirus (HPV)16 and 18 infections, spreads through sexual contact, and tends to become cancerous. Currently, there are different BP treatment methods, and few reports on the efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) (ALA-PDT). We compared the differences in the clearance and recurrence rates of BP between the ALA-PDT group and other groups, and explored methods to improve clinical effects and reduce lesion recurrence by combining clinical retrospective data. METHODS: We enrolled patients who were diagnosed with bowel papulosis" between January 1, 2009, and December 31, 2020. Patient information, such as ID number, hospitalization number, admission time, name, age, gender, telephone number, admission record, discharge record, outpatient medical history, HPV type analysis, histopathological examination, and treatment plan were recorded. Outcomes were obtained and recorded through outpatient visits, telephone, and online follow-ups from patients who had reached the treatment endpoint. We compared and evaluated the differences in lesion clearance rate, lesion recurrence rate, and patient satisfaction between the ALA-PDT group and other groups using statistical analysis. RESULTS: The lesion clearance rate of the ALA-PDT group was significantly higher than that of the control group, the lesion recurrence rate was lower than that of the control group, and patient satisfaction was higher than that of the control group. The lesion clearance rate of the ALA-PDT group was higher than that of the microwave and radiofrequency groups, the lesion recurrence rate of the ALA-PDT group was significantly lower than that of the microwave and radiofrequency groups, and patient satisfaction was significantly higher than that of the microwave and radiofrequency groups. In the lesions of patients with BP, in addition to HPV16 and HPV18 types, other types were also detected, and most of them were mixed types of HPV infection. Age, sex, and duration of disease were not risk factors that affected BP recurrence. CONCLUSIONS: ALA-PDT for BP has the advantages of high lesion clearance rate, low lesion recurrence rate, and high patient satisfaction. ALA-PDT is worthy of recommendation as a preferred treatment plan for the treatment of BP.

Photodynamic therapy combined with surgical management of extensive anogenital condylomatosis in a patient with systemic lupus erythematosus.

Infections with human papillomavirus in the anogenital area result in warty, papillary, and condylomatous lesions. The giant anogenital wart is relatively uncommon. Treatment of giant wart is challenging, especially in the immunosuppressive population. Here, a patient with systemic lupus erythematosis had extensive, fast-growing, recurrent anogenital condylomatosis shaped as giant cauliflowers. We reported this case and the successful treatment of photodynamic therapy combined with surgical management. It provided the feasibility for surgical ablation combined with ALA-PDT performed for these kinds of challenging cases.

ALA-PDT combined with cystoscopy: A method to eliminate refractory HPV infection in a patient with condyloma acuminata.

BACKGROUND: Condyloma acuminata is a common sexually transmitted disease for which an underlying chronic human papillomavirus (HPV) infection is an important cause of recurrence. 5-aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) has become an effective method to treat condyloma acuminata. Urinary tract condyloma acuminata are not considered common, but warts in the bladder can be detected by cystoscopy. OBJECTIVE: To treat a urinary tract HPV infection in a 35 years old woman diagnosed with condyloma acuminata and to eliminate HPV infection. METHOD: A total of six sessions of ALA-PDT to the cervix and seven sessions of ALA-PDT to the vagina were executed, and the patient subsequently had a cystoscope examination. The wart in the bladder was found by cystoscopy and cauterized with radiofrequency. RESULT: Internal urethra, urethral orifice, cervical, vaginal, and vulvar HPV-DNA detection eventually all returned negative results, and there was no recurrence with two years of follow-up.

Therapeutic evaluation of 5-aminolevulinic acid-mediated photodynamic therapy in Bowenoid papulosis.

BACKGROUND: Bowenoid papulosis is a polymorphic papular disease that occurs on the external genital area. We investigated the efficacy of 5-aminolevulinic acid-mediated photodynamic therapyin the treatment of Bowenoid papulosis. METHODS: We investigated 200 Bowenoid papulosis cases from the Department of Dermatology and Venereology of Nanfang Hospital in 2016-2018. Biopsies were performed from Bowenoid papulosis lesions before treatment. The patients were divided into two groups: 100 patients each in the 5-aminolevulinic acid-mediated photodynamic therapy and control groups(radiofrequency cauterisation, microwave ablation, and surgical resection groups). Differences in lesion clearance, recurrence rate, and patient satisfaction after treatment were evaluated. RESULTS: Photodynamic therapy sessions for multifocal Bowenoid papulosis were more frequent than those for monofocal lesions. All lesions in the 5-aminolevulinic acid-mediated photodynamic therapy group were cleared after photodynamic therapy, with no recurrence at the 1-year follow-up; however, 20 (20.0 %) patients in the control showed recurrence after 1 year. Only 5patients in the photodynamic group were unsatisfied with the treatment cost and 34 patients in the control group experienced short-term pain and scarring. The recurrence rate was significantly lower (P < 0.05) and patient satisfaction was higher (P < 0.05) in the 5-aminolevulinic acid-mediated photodynamic therapy group than those in the control. The recurrence rate was significantly lower (P < 0.05) and patient satisfaction was higher (P < 0.05) in the 5-aminolevulinic acid-mediated photodynamic therapy group than those in the surgical resection group. The recurrence rate of lesions was significantly lower in the surgical resection group than that in the rest of the control group (P < 0.05). There was no difference in recurrence rate and patient satisfaction between the radiofrequency cauterisation and microwave ablation groups. CONCLUSIONS: 5-aminolevulinic acid-mediated photodynamic therapy for Bowenoid papulosis results in a low recurrence rate and high satisfaction.

Evaluation of human papillomavirus DNA detection-guided aminolaevulinic acid-mediated photodynamic therapy for the treatment of condyloma acuminata.

BACKGROUND: Aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) is used to treat condyloma acuminata (CA), yielding a high clearance rate and low recurrence rate. Consecutive human papillomavirus (HPV) DNA detection can be used to dynamically monitor the therapeutic efficiency of PDT. Here, we evaluated the efficacy of ALA-PDT in the context of different HPV infection states. METHODS: One hundred thirty-eight patients with HPV infection and visible anogenital warts were enrolled. Microwave or radiofrequency was used to remove visible lesions before PDT. HPV DNA detection was performed using real-time polymerase chain reaction before each PDT session and at follow-up. Treatment was halted after the patient showed two negative results for HPV DNA detection in a row. RESULTS: Of the 138 patients enrolled in the study, 72 completed treatment. Multisite HPV-infected patients required more sessions of PDT than did single-site infected patients to reach the endpoint of treatment. Compared with patients with only external CA, individuals with internal CA required more sessions to eliminate HPV infection. The total number of PDT sessions performed in the multitype HPV-infected group was significantly higher than that in the single-type infected group. Patients with non-high-risk (HR)-HPV infection required fewer PDT sessions than did those with HR-HPV infection by the end of treatment. Sixty-nine patients were followed-up for at least 6 months, only 2.9% of whom showed recurrence. CONCLUSIONS: Combined ALA-PDT and HPV DNA detection was an effective strategy for the treatment of CA. Patients with multisite and multitype HPV infection required more PDT sessions to eliminate the virus.

Photodynamic therapy in a patient with facial angiofibromas due to tuberous sclerosis complex.

The facial angiofbromas due to tuberous sclerosis complex produced significant social and emotional distress for affected individuals, but there is no specific therapeutic strategy up to now. Herein, we report a case of facial angiofibromas successfully treated by 5-aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) with no recurrence for 6 years, thus providing a promising therapeutic option.

Human papillomavirus DNA detection-guided ALA-photodynamic therapy for anogenital condyloma acuminata: A report of two cases.

5-aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) is a highly effective, safe, and promising treatment for human papillomavirus (HPV)-induced anogenital condyloma acuminata (CA). Specific HPV subtypes are responsible for the pathogenesis of CA and dynamic changes in viral loads may reflect the efficiency of PDT. Here we present two cases of anogenital CA successfully treated by ALA-PDT under the guidance of HPV DNA detection including genotype identification and viral load measurement, which provided clues for unexpected intra-anal infection. Both of these male patients were free of detectable HPV at the end of the treatment and no recurrence was observed after 1 year. We conclude that the HPV DNA detection can accurately guide ALA-PDT, indicate unnoticed lesions, as well as improve and evaluate the efficiency.

5-aminolevulinic acid photodynamic therapy for condyloma acuminatum of urethral meatus.

Objectives: Condyloma acuminatum are the most common sexually transmitted diseases worldwide, and they are closely associated with human papillomavirus (HPV) infection. Urethral meatus is one of the places that warts occur. Many treatments for uretheral warts have limitations. In this study, we performed 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) on patients and investigated the effectiveness of reducing HPV viral loads. Materials and Methods: In our study, 21 patients diagnosed with urethral condyloma acuminatum were included. After 4 h treatment of ALA, patients received PDT. Each patient received HPV test before every PDT cycle. The frequency of PDT was dependent on viral load changes. Results: All patients achieved complete clinical remission after the last session of ALA-PDT. There were significant differences in HPV viral loads between pretherapy and after one or three rounds of PDT treatment. Conclusions: ALA-PDT is a safe and effective method for treatment of condyloma acuminatum in urethra meatus. Dynamic monitoring of HPV viral loads can more objectively demonstrate the effectiveness and guide the treatment of PDT.

5-aminolevulinic acid photodynamic therapy for anal canal condyloma acuminatum: A series of 19 cases and literature review.

BACKGROUND: Anal canal condyloma acuminata are common, sexually transmitted lesions, most often caused by the human papillomavirus. The relatively high recurrence rate of anal canal condyloma acuminata can be attributed to the unsuccessful elimination of viruses in areas of subclinical and latent infection. This study aimed to observe and evaluate the effectiveness of 5-aminolevulinic acid-photodynamic therapy combined with monitoring of human papillomavirus load changes in patients with anal canal condyloma acuminata. METHODS: A total of 19 patients with anal genital warts were recruited for this study. Firstly, visible warts around the anus were removed. Next, an anoscope examination was performed. Human papillomavirus detection, using real-time polymerase chain reaction assays, was performed before every cycle of treatment. Absorbent cotton rolls soaked with a concentration of 20% 5-aminolevulinic acid were inserted into the anus for 3 h. Finally, photodynamic therapy was applied to the lesions. Each patient required multiple PDT sessions to achieve complete response. RESULTS: All patients achieved complete clinical remission one week after the last session of treatment, and human papillomavirus loads decreased significantly. Six months follow-up after completion of therapy, none of the patients had recurrence. CONCLUSIONS: 5-aminolevulinic acid-photodynamic therapy is an effective and safe approach for anal canal condyloma acuminata. Dynamic human papillomavirus viral quantitative monitoring can aid in the evaluation of therapeutic effects and lead to better treatment outcomes.

Treatment of latent or subclinical Genital HPV Infection with 5-aminolevulinic acid-based photodynamic therapy.

BACKGROUND: Genital HPV infections are widely prevalent. HPV can persist and be transmitted to partners even after warts are gone. The HPV genotype and viral load assay can reveal whether infections are persistent or latent, and it can serve as a predictor of infection clearance. Although numerous studies have demonstrated that photodynamic therapy (PDT) is effective against condyloma acuminata, there is no data on its effects on latent, persistent infections. METHODS: A total of 20 patients with latent or subclinical HPV infection were evaluated. At each patient visit, polymerase chain reaction was used to identify HPV genotypes and measure the viral loads, which reflect the status of HPV infection. We administered 5-aminolevulinic acid (ALA)-based PDT weekly for patients with active infections, while no treatment was administered to patients with regressing infections. RESULTS: PDT treatment can effectively eliminate HPV, significantly reducing viral loads after three rounds of treatment (p < 0.001). The rate of negative HPV DNA test results was higher in patients with latent or subclinical infections than in patients with genital warts after one round of PDT treatment. CONCLUSIONS: ALA-PDT can effectively eliminate latent or subclinical HPV infections. Additionally, our assay for identifying HPV genotypes and viral loads, which reflect the status of HPV infection, can accurately guide ALA-PDT treatment.

Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts.

BACKGROUND: Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. METHODS: Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. RESULTS: HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. CONCLUSIONS: Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV.

HDAC6 Suppresses Age-Dependent Ectopic Fat Accumulation by Maintaining the Proteostasis of PLIN2 in Drosophila.

Age-dependent ectopic fat accumulation (EFA) in animals contributes to the progression of tissue aging and diseases such as obesity, diabetes, and cancer. However, the primary causes of age-dependent EFA remain largely elusive. Here, we characterize the occurrence of age-dependent EFA in Drosophila and identify HDAC6, a cytosolic histone deacetylase, as a suppressor of EFA. Loss of HDAC6 leads to significant age-dependent EFA, lipid composition imbalance, and reduced animal longevity on a high-fat diet. The EFA and longevity phenotypes are ameliorated by a reduction of the lipid-droplet-resident protein PLIN2. We show that HDAC6 is associated physically with the chaperone protein dHsc4/Hsc70 to maintain the proteostasis of PLIN2. These findings indicate that proteostasis collapse serves as an intrinsic cue to cause age-dependent EFA. Our study suggests that manipulation of proteostasis could be an alternative approach to the treatment of age-related metabolic diseases such as obesity and diabetes.

Plants' use of different nitrogen forms in response to crude oil contamination.

In this study, we investigated Phragmites australis' use of different forms of nitrogen (N) and associated soil N transformations in response to petroleum contamination. 15N tracer studies indicated that the total amount of inorganic and organic N assimilated by P. australis was low in petroleum-contaminated soil, while the rates of inorganic and organic N uptake on a per-unit-biomass basis were higher in petroleum-contaminated soil than those in un-contaminated soil. The percentage of organic N in total plant-assimilated N increased with petroleum concentration. In addition, high gross N immobilization and nitrification rates relative to gross N mineralization rate might reduce inorganic-N availability to the plants. Therefore, the enhanced rate of N uptake and increased importance of organic N in plant N assimilation might be of great significance to plants growing in petroleum-contaminated soils. Our results suggest that plants might regulate N capture under petroleum contamination.