Novel chlorin e6-based conjugates of tyrosine kinase inhibitors: Synthesis and photobiological evaluation as potent photosensitizers for photodynamic therapy.

Since tyrosine kinase inhibitor (TKI) could reverse ABCG2-mediated drug-resistance, novel chlorin e6-based conjugates of Dasatinib and Imatinib as photosensitizer (PS) were designed and synthesized. The results demonstrated that conjugate 10b showed strongest phototoxicity against HepG2 and B16-F10 cells, which was more phototoxic than chlorin e6 and Talaporfin. It could reduce efflux of intracellular PS by inhibiting ABCG2 in HepG2 cells, and localize in mitochondria, lysosomes, golgi and ER, resulting in higher cell apoptosis rate and ROS production than Talaporfin. Moreover, it could induce cell autophagy and block cell cycle in S phase, and significantly inhibit tumor growth and prolong survival time on BALB/c nude mice bearing HepG2 xenograft tumor to a greater extent than chlorin e6. Consequently, compound 10b could be applied as a promising candidate PS due to its good water-solubility and stability, low drug-resistance, high quantum yield of 1O2 and excellent antitumor efficacy in vitro and in vivo.

Phosphorus limitation induced by nitrogen addition changed soil microbial community structure in a subtropical Pinus taiwanensis forest.

Soil microorganisms play an important role in the biogeochemical cycles of terrestrial ecosystems. How-ever, it is still unclear how the amount and duration of nitrogen (N) addition affect soil microbial community structure and whether there is a correlation between the changes in microbial community structure and their nutrient limi-tation status. In this study, we conducted an N addition experiment in a subtropical Pinus taiwanensis forest to simulate N deposition with three treatments: control (CK, 0 kg N·hm-2·a-1), low N (LN, 40 kg N·hm-2·a-1), and high N (HN, 80 kg N·hm-2·a-1). Basic soil physicochemical properties, phospholipid fatty acids content, and carbon (C), N and phosphorus (P) acquisition enzyme activities were measured after one and three years of N addition. The relative nutrient limitation status of soil microorganisms was analyzed using ecological enzyme stoichiometry. The results showed that one-year N addition did not affect soil microbial community structure. Three-year LN treatment significantly increased the contents of Gram-positive bacteria (G+), Gram-negative bacteria (G-), actinomycetes (ACT), and total phospholipid fatty acids (TPLFA), whereas three-year HN treatment did not significantly affect soil microbial community, indicating that bacteria and ACT might be more sensitive to N addition. Nitrogen addition exacerbated soil C and P limitation. Phosphorus limitation was the optimal explanatory factor for the changes in soil microbial community structure. It suggested that P limitation induced by N addition might be more beneficial for the growth of certain oligotrophic bacteria (e.g. G+) and the microorganisms participating in the P cycling (e.g. ACT), with consequences on soil microbial community structure of subtropical Pinus taiwanensis forest.

[Effects of different carbon addition modes on the soil priming effect of a subtropical Phyllostachys edulis forest under nitrogen deposition]. / æ°®æ²‰é™ä¸‹ä¸åŒç¢³æ·»åŠ æ¨¡å¼å¯¹äºšçƒ­å¸¦æ¯›ç«¹æž—åœŸå£¤æ¿€å‘æ•ˆåº”çš„å½±å“.

Priming effect (PE) plays an important role in regulating terrestrial soil carbon (C) cycling, but the impact of different C addition modes on the PE in subtropical forest ecosystems with increasing nitrogen (N) deposition is unclear. In this study, we investigated the effects of C addition patterns (single or repeated C addition) on soil PE by adding 13C-labeled glucose for 90 d in an incubation experiment with different levels of N application (0, 20, and 80 kg N·hm-2·a-1). The different patterns of glucose addition significantly increased soil organic C (SOC) mineralization and produced positive PE. Single glucose addition resulted in stronger PE than repeated addition. PE was significantly weakened with increasing N application levels, indicating that N deposition inhibited soil excitation in Phyllostachys edulis forests. The cumulative PE was significantly negatively correlated with ß-N-acetylaminoglucosidase (NAG) and peroxidase (PEO) activities, and was significantly positively correlated with microbial biomass P (MBP) and potential of hydrogen (pH). Our findings indicated that, when acting together on soil, N application and C addition could strongly affect soil C stocks by stimulating the mineralization of native soil organic matter in subtropical forests. The findings further indicated that single C addition model might overestimate the effect of exogenous readily decomposable organic C on PE and ignore the effect of N deposition on PE, which in turn would overestimate the mineralization loss of forest SOC.

Immunogenicity and safety of two-dose SARS-CoV-2 vaccination via different platforms in kidney transplantation recipients.

After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVC-COV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics.

[Effects of nitrogen addition on the kinetic parameters of soil acid phosphomonoesterase in a Moso bamboo forest]. / æ°®æ·»åŠ å¯¹æ¯›ç«¹æž—åœŸå£¤é ¸æ€§ç£·é ¸å•é ¯é ¶åŠ¨åŠ›å­¦å‚æ•°çš„å½±å“.

Soil phosphatases are important in the mineralization of organophosphates and in the phosphorus (P) cycle. The kinetic mechanisms of phosphatases in response to nitrogen (N) deposition remain unclear. We carried out a field experiment with four different concentrations of N: 0 g N·hm-2·a-1(control), 20 g N·hm-2·a-1(low N), 40 g N·hm-2·a-1(medium N), and 80 g N·hm-2·a-1(high N) in a subtropical Moso bamboo forest. Soil samples were then collected from 0 to 15 cm depth, after 3, 5 and 7 years of N addition. We analyzed soil chemical properties and microbial biomass. Acid phosphatase (ACP) was investigated on the basis of maximum reaction velocity (Vm), Michaelis constant (Km), and catalytic efficiency (Ka). Results showed that N addition significantly decreased soil dissolved organic carbon (DOC), available phosphorus, and organophosphate content, but significantly increased soil ammonium, nitrate-N content, and Vm. There was a significant relationship between Vm and the concentrations of available phosphorus, organophosphate, and soil DOC. In general, N addition substantially increased Ka, but did not affect Km. The Km value in the high N treatment group was higher than that in the control group after five years of N addition. Km was significantly negatively associated with both available phosphorus and organophosphate. Medium and high N treatments had stronger effects on the kinetic parameters of ACP than low N treatment. Results of variation partition analysis showed that changes in soil chemical properties, rather than microbial biomass, dominated changes in Vm(47%) and Km(33%). In summary, N addition significantly affected substrate availability in Moso bamboo forest soil and modulated soil P cycle by regulating ACP kinetic parameters (especially Vm). The study would improve the understanding of the mechanisms underlying soil microorganisms-regulated soil P cycle under N enrichment. These mechanisms would identify the important parameters for improving soil P cycling models under global change scenarios.

Survey of factors associated with the willingness toward living kidney donation.

BACKGROUND: Living donor kidney transplantation (LDKT) is an important organ resource, especially in countries with low deceased donation rates. Strategies for expanding access to transplantation should be developed by identifying the modifiable factors. In this study, we evaluated these factors in the relatives of patients from both medical centers and dialysis clinics using questionnaires. METHODS: The questionnaires were anonymous and confidential. We collected questionnaires from previous donors, relatives of patients on the waitlist in the medical center, and relatives of dialysis patients in three nephrology clinics. The study groups were divided into three categories: donor group (n = 68), willing group (n = 43), and non-donor group (n = 65). RESULTS: Respondents in the clinics had lower cognition and willingness towards LDKT than those in the medical center. More knowledge of LDKT, better relationship with patients, more familial support, and female gender were positively related to donation. The non-donor group tended to want to maintain an intact body for the afterlife. There was no significant difference in age, educational degree, average monthly income, and medical compliance among the three groups. CONCLUSION: More efforts need to be made in dialysis clinics, where general nephrologists are important for the outreach of information. In addition, dealing with religious ambivalence and reestablishing cultural mindsets with health education programs are important issues in a non-Christian country.

[Soil enzyme stoichiometry revealed the changes of soil microbial carbon and phosphorus limitation along an elevational gradient in a Pinus taiwanensis forest of Wuyi Mountains, Southeast China]. / åœŸå£¤é ¶è®¡é‡æ­ç¤ºäº†æ­¦å¤·å±±é»„å±±æ¾æž—åœŸå£¤å¾®ç”Ÿç‰©æ²¿æµ·æ‹”æ¢¯åº¦çš„ç¢³ç£·é™åˆ¶å˜åŒ–.

Understanding changes in soil enzyme activities and ecoenzymatic stoichiometry is important for assessing soil nutrient availability and microbial nutrient limitation in mountain ecosystems. However, the variations of soil microbial nutrient limitation across elevational gradients and its driving factors in subtropical mountain forests are still unclear. In this study, we measured soil properties, microbial biomass, and enzyme activities related to carbon (C), nitrogen (N), and phosphorus (P) cycling in Pinus taiwanensis forests at different altitudes of Wuyi Mountains. By analyzing the enzyme stoichiometric ratio, vector length (VL), and vector angle (VA), the relative energy and nutrient limitation of soil microorganisms and its key regulatory factors were explored. The results showed that ß-glucosaminidase (BG) activities increased along the elevational gradient, while the activities of ß-N-acetyl glucosaminidase (NAG), leucine aminopeptidase (LAP), acid phosphatase (AcP) and (NAG+LAP)/microbial biomass carbon (MBC) and AcP/MBC showed the opposite trend. Enzyme C/N, enzyme C/P, enzyme N/P, and VL were enhanced with increasing elevation, while VA decreased, indicating a higher degree of microbial P limitation at low elevation and higher C limitation at high elevation. In addition, our results suggested that dissolved organic carbon and microbial biomass phosphorus are critical factors affecting the relative energy and nutrient limitation of soil microorganisms at different elevations. The results would provide a theoretical basis for the responses of soil carbon, nitrogen, and phosphorus availability as well as the relative limitation of microbial energy and nutrition to elevational gradients, and improve our understanding of soil biogeochemical cycle process in subtropical montane forest ecosystems.

Circuitous Path to Live Donor Liver Transplantation from the Coordinator's Perspective.

Background: The live donor liver transplantation (LDLT) process is circuitous and requires a considerable amount of coordination and matching in multiple aspects that the literature does not completely address. From the coordinators' perspective, we systematically analyzed the time and risk factors associated with interruptions in the LDLT process. Methods: In this retrospective single center study, we reviewed the medical records of wait-listed hospitalized patients and potential live donors who arrived for evaluation. We analyzed several characteristics of transplant candidates, including landmark time points of accompanied live donation evaluation processes, time of eventual LDLT, and root causes of not implementing LDLT. Results: From January 2014 to January 2021, 417 patients (342 adults and 75 pediatric patients) were enrolled, of which 331 (79.4%) patients completed the live donor evaluation process, and 205 (49.2%) received LDLT. The median time from being wait-listed to the appearance of a potential live donor was 19.0 (interquartile range 4.0-58.0) days, and the median time from the appearance of the donor to an LDLT or a deceased donor liver transplantation was 68.0 (28.0-188.0) days. The 1-year mortality rate for patients on the waiting list was 34.3%. Presence of hepatitis B virus, encephalopathy, and hypertension as well as increased total bilirubin were risk factors associated with not implementing LDLT, and biliary atresia was a positive predictor. The primary barriers to LDLT were a patient's critical illness, donor's physical conditions, motivation for live donation, and stable condition while on the waiting list. Conclusions: Transplant candidates with potential live liver donors do not necessarily receive LDLT. The process requires time, and the most common reason for LDLT failure was critical diseases. Aggressive medical support and tailored management policies for these transplantable patients might help reduce their loss during the process.

Hybridization of Particulate Methane Monooxygenase by Methanobactin-Modified AuNPs.

Particulate methane monooxygenase (pMMO) is a characteristic membrane-bound metalloenzyme of methane-oxidizing bacteria that can catalyze the bioconversion of methane to methanol. However, in order to achieve pMMO-based continuous methane-to-methanol bioconversion, the problems of reducing power in vitro regeneration and pMMO stability need to be overcome. Methanobactin (Mb) is a small copper-chelating molecule that functions not only as electron carrier for pMMO catalysis and pMMO protector against oxygen radicals, but also as an agent for copper acquisition and uptake. In order to improve the activity and stability of pMMO, methanobactin-Cu (Mb-Cu)-modified gold nanoparticle (AuNP)-pMMO nanobiohybrids were straightforwardly synthesized via in situ reduction of HAuCl4 to AuNPs in a membrane fraction before further association with Mb-Cu. Mb-Cu modification can greatly improve the activity and stability of pMMO in the AuNP-pMMO nanobiohybrids. It is shown that the Mb-Cu-modified AuNP-pMMO nanobiohybrids can persistently catalyze the conversion of methane to methanol with hydroquinone as electron donor. The artificial heterogeneous nanobiohybrids exhibited excellent reusability and reproducibility in three cycles of catalysis, and they provide a model for achieving hydroquinone-driven conversion of methane to methanol.

Efficacy and Safety Evaluation of Picosecond Alexandrite Laser with a Diffractive Lens Array for Treatment of Melasma in Asian Patients by VISIA Imaging System.

Objective: To evaluate the efficacy and safety of picosecond (ps) 755-nm alexandrite laser with a diffractive lens array (DLA) generating laser-induced optical breakdown, which may be beneficial for melasma treatment. Background: Melasma is notorious for difficult to treat with any modality setting. Recently, picosecond alexandrite laser with DLA seems promising for dealing with it without intolerable complications. Methods: Twenty (N = 20) Asian female melasma patients with Fitzpatrick skin type IV were recruited for 3 treatment sessions of picosecond 755-nm alexandrite laser with DLA at a 4- to 6-week interval. The pulse duration was 750 ps. An 8-mm spot size and the fluence of 0.4 J/cm2 was used over the target area with 2 passes per treatment area and around 2000-2500 passes in total. The repetition rate was 10 Hz. Melasma Area and Severity Index (MASI) score and VISIA® imaging system analysis were utilized for evaluation before treatment and 4 weeks after the completion of the third treatment session. The clinical improvement and adverse events were assessed by the physicians and patients, respectively. Results: The median age of the patients was 45 years (from 27 to 55 years). In the physicians' evaluation, 40% (n = 8) of patients showed good improvement and 40% (n = 8) of patients showed moderate improvement. The mean MASI score before and after laser therapy showed significant improvement from 9.0 ± 4.8 to 6.5 ± 3.7 (p < 0.001). VISIA analysis of the forehead presented significant improvement in spots (p = 0.007) and porphyrins (p = 0.032). Some patients experienced erythema (25%), pruritus (20%), and scaling (20%) but subsided within few days of using emollients and sunscreen. Only 5% (n = 1) of patients developed mild postinflammatory hyperpigmentation, which also subsided in 3 weeks. Conclusions: Three sessions of picosecond 755-nm alexandrite laser with a DLA were effective for melasma treatment in Asian patients with minimal side effects.

Effects of mycophenolate mofetil on cutaneous lupus erythematosus in (NZB × NZW) F1 mice.

BACKGROUND: Few studies have evaluated the effects and precise molecular mechanism of mycophenolate mofetil (MMF) in the treatment of human cutaneous lupus erythematosus (CLE). Our findings shed light on the therapeutic effects of MMF in a UVB-induced NZB × NZW (NZBW) F1 CLE mouse model. METHODS: Continuous MMF treatment (60 mg/kg/day) was administered up to Day 50 from the beginning of UVB induction (Day 0; 20 weeks old), as the pathologic features of CLE are present after 50 days. The therapeutic effects of MMF treatment in NZBW lupus mice were examined by comparing histopathological changes, lupus band test (deposition of immune complexes at the dermal-epidermal junction) and colocalization of autoantibodies with a dermal autoantigen Dsg3, and by evaluating the associations of local matrix metalloprotease activities. RESULTS: MMF improved survival in the NZBW lupus mice from 35.7% to 81.8%. The proteinuria, blood urea nitrogen, and interleukin 6 levels were significantly reduced after MMF treatment. The dermal lymphocytic infiltration, deposition of immune complexes at the dermal-epidermal junction, colocalized autoantibodies with Dsg3, and epidermal matrix metalloprotease activity were also attenuated in MMF-treated NZBW F1 mice. CONCLUSION: The results confirmed that MMF could substantially attenuate skin damage due to CLE in the NZBW F1 mouse model.