Dual-acceptor engineering of donor-acceptor type molecules for all-round boosting anti-tumor phototherapy

The integration of robust photon-absorption capacity,high reactive oxygen speciesyields and photothermal conversion efficiency(PCE)into a single phototheranosticnano-agents is ideal but rarely reported.This study employed a dual-acceptorengineering strategy utilizing isoindigo and selenium-substituted[1,2,5]thiadiazolo[3,4-c]pyridine to augment the molar extinction coefficient and spin-orbitcoupling effect,respectively,resulting in a substantial enhancement of photonabsorptionability and non-radiative decay energy-release process of donoracceptortype phototherapy molecules.As the optimal phototherapy agent,IID-PSe exhibited a high molar extinction coefficient two times that of photosensitizer,excellent 1O2 yield(15%)and PCE(34%),exhibiting great potential forphototherapy.After encapsulating with DSPE-PEG2000,IID-PSe NPs showedexcellent anti-tumor phototherapy ability both in vitro and in vivo.This workprovides an effective idea for designing high-performance photosensitive dyeswith high efficiency phototherapy output.

Dynamic expression of nerve growth factor and its receptor Trk A after subarachnoid hemorrhage in rat brain

Delayed ischemic neurologic deficit after subarachnoid hemorrhage results from loss of neural cells.Nerve growth factor and its receptor Trk A may promote regeneration of neural cells,but their expression after subarachnoid hemorrhage remains unclear.In the present study,a rat model of subarachnoid hemorrhage was established using two injections of autologous blood into the cistern magna.Immunohistochemical staining suggested that the expression of nerve growth factor and Trk A in the cerebral cortex and brainstem increased at 6 hours,peaked at 12 hours and decreased 1 day after induction of subarachnoid hemorrhage,whereas the expression in the hippocampus increased at 6 hours,peaked on day 1,and decreased 3 days later.Compared with those for the rats in the sham and saline groups,neurobehavioral scores decreased significantly 12 hours and 3 days after subarachnoid hemorrhage（P 〈 0.05）.These results suggest that the expression of nerve growth factor and its receptor Trk A is dynamically changed in the rat brain and may thus participate in neuronal survival and nerve regeneration after subarachnoid hemorrhage.

Se-substituted pentamethine cyanine for anticancer photodynamic therapy mediated using the hot band absorption process

Photodynamic therapy(PDT)is a promising cancer treatment modality owing to its high spatiotempora selectivity and noninvasive nature.However,conventional photosensitizers(PSs)used in PDT are respon sive only to visible light,which makes them unsuitable for tissue penetration.In this study,we propose a PS based on hot band absorption(HBA),which can be triggered by anti-Stokes light at 808 nm via a one-photon process.The introduction of selenium(Se)into pentamethine cyanine(Secy5)not only facili tates intersystem crossing for reactive oxygen species(ROS)production but also enhances HBA efficiency thereby prolonging the excitation wavelength.In addition,Secy5 demonstrates excellent biocompatibility unlike its I-substituted counterpart(Icy5),and produces not only^(1)O_(2)but also O_(2)^(·-),making it a desirable candidate for treating hypoxic solid tumors.According to the results of in vivo and in vitro experiments Secy5 can efficiently inhibit cancer cell growth via anti-Stokes activation processes,thereby providing a novel approach to design anti-Stokes excitation PSs for anticancer treatment.

THE IMPACT OF TROPICAL CYCLONES ON CHINA IN 2016

In 2016, the Northwest Pacific and the South China Sea registered the genesis of 26 tropical cyclones. 8 of them, including NEPARTAK(1601), MIRINAE(1603), NIDA(1604), DIANMU(1608), MERANTI(1614),MEGI(1617), SARIKA(1621) and HAIMA(1622), made landfall over China's coastal areas. The number one TC of 2016, NEPARTAK, was named on July 3. Although no typhoon generated in the first half of this year,which means 4.6 incidences less compared with the same period of a normal year, more tropical cyclones made landfall over China(the historical average in the same period of 1949-2015 is 6.7). And these 8 tropical cyclones had an averaged intensity up to 40.6 m/s, significantly enhanced compared with the multi-year average of 32.8 m/s.The death toll from the 11 tropical cyclones affected China in 2016 is 206. MERANTI was the most destructive one in 2016, which brought up the largest numbers of affected and evacuated population, damaged houses and direct economic losses. In 2016, China Meteorological Administration(CMA) 24-120 h mean official track forecast errors were 66, 127, 213, 292 and 364 km, respectively. The 24 h track forecast error has been kept within 70 km in two consecutive years.

A 10-year follow-up of electric acupuncture for lumbar disc herniation and sciatica

Background:Lumbar disc herniation and sciatica are major causes of disability in health care.A variety of non-operative treatments are available,include acupuncture,while there is little long-term evidence to indicate efficacy of acupuncture.Objective:To observe the long-term clinical effects of lumbar disc herniation and sciatica treated by acupuncture.Methods:Based on acupuncture point selections of the traditional Chinese medicine meridian theory,we developed the treatment strategies for acupuncture in a consensus process with the author's clinical and teaching practice.All 112 outpatients previously visited orthopedic surgeons or neurosurgeons and underwent(magnetic resonance imaging)MRI studies prior to having electric acupuncture treatment.This study used Oswestry Disability Index(ODI)-self-comparison and showed that acupuncture treatments for lumber disc herniation and sciatica demonstrated significant improvement in long term clinical outcomes.A total of 112 lumbar disc herniation and sciatica cases were treated with electric acupuncture for pain relief and function improvement from July 1998 to December 2006.Results:All the 112 cases filled out the ODI forms prior to receiving treatment.Among the 112 patients,23 of them did not finish the 6-week treatments.89 cases were evaluated with ODI after 6-week acupuncture treatments.Of those 89 cases,67 cases were followed up with ODI 10 years later.Significant improvement from the pre-to post-acupuncture ODI scores was observed(P<0.05).The 10-year follow-up ODI showed significant improvement with long-term results(P<0.05).Conclusion:Electric acupuncture for lumbar disc herniation and sciatica showed satisfactory long-term clinical effects.

Accelerated antibacterial red-carbon dots with photodynamic therapy against multidrug-resistant Acinetobacter baumannii

The emergence of antibiotic resistance in bacteria is a major public-health issue.Synthesis of efficient antibiotic-free material is very important for fighting bacterial infection-related diseases.Herein,red-carbon dots(R-CDs)with a broad range of spectral absorption(350–700 nm)from organic bactericides or intermediates were synthesized through a solvothermal route.The prepared R-CDs not only had intrinsic antibacterial activities,but also could kill multidrug-resistant bacteria(multidrug-resistant Acinetobacter baumannii(MRAB)and multidrug-resistant Staphylococcus aureus(MRSA))effectively by generating reactive oxygen species.Furthermore,R-CDs could eliminate and inhibit the formation of MRAB biofilms,while conferring few side effects on normal cells.A unique property of R-CDs was demonstrated upon in vivo treatment of antibiotic-sensitive MRABinduced infected wounds.These data suggested that this novel R-CDs-based strategy might enable the design of nextgeneration agents to fight drug-resistant bacteria.

Consensus on the Diagnosis and Treatment of Melasma in China (2021 Version)

The pathogenesis of melasma is believed to be related to heredity,sun exposure,sex hormones,and other factors.The mechanisms underlying the development of melasma include increased melanin synthesis,vascular proliferation within the skin lesions,inflammation,and skin barrier dysfunction.The diagnosis of melasma is mainly based on clinical manifestations and noninvasive techniques.Coupling with recent research progress in melasma,the present consensus comprehensively elaborates the etiology,pathogenesis,clinical manifestations,staging,classification,diagnosis,and treatment of melasma to improve the diagnostic and therapeutic skills of Chinese dermatologists.

Consensus on the Diagnosis and Treatment of Vitiligo in China(2021 Revision)#

Vitiligo is a common depigmented skin disease that negatively affects the physical and mental health of patients.The 2018 version of the Vitiligo Treatment Consensus has been updated based on the research progress on vitiligo in the past 3 years in combination with the clinical experiences of experts.The newly revised points include maintenance therapy,early glucocorticoid intervention,and oral mini-pulsed glucocorticoid administration protocols.The prospect of using JAK inhibitors in the treatment of vitiligo is also discussed.

SINS model in the management of biosafety level 2 laboratories: exploration and practice

A significant number of biosafety level 2(BSL-2)laboratories have been established in many countries for studies of various types of pathogenic agents and other infectious biological materials.The harmonized management of biological risks in such diverse laboratories thus appears as a real challenge.Zhejiang Province in China has taken the initiative to establish a comprehensively integrated laboratory biosafety management system called SINS(Standardization,Informatization,Normalization and Systematization).The SINS model system has been introduced and adopted in 1,721 BSL-2 laboratories in Zhejiang Province,and thus lead to an increase in the number of biosafety committees from 20%to more than 95%from 2007 to 2018,and the number of biosafety laboratory managers who knows biosafety-related laws and regulations increase from 52.7%to 83.7%from 2009 to 2017.Such achievements indicate that the successful implementation of SINS model has increased the effective control of biological risks in BSL-2 laboratories of the Zhejiang Province.SINS model and its main effects on leading the improvement of laboratory biosafety management was presented in this review.The SINS model helps to strengthen laboratory biosafety and thus effectively reduces occurrence of biosafety-related incidences.This model can potentially be used by other regions or countries where harmonized biosafety management system is still under-developing.

Brainstem auditory evoked potential combined with high resolution cranial base CT can optimize the diagnosis of auditory nerve injury

Purpose:Auditory nerve injury is one of the most common nerve injury complications of skull base fractures.However,there is currently a lack of auxiliary examination methods for its direct diagnosis.The purpose of this study was to find a more efficient and accurate means of diagnosis for auditory nerve injury.Methods:Through retrospectively analyzing the results of brainstem auditory evoked potential(BAEP)and high-resolution CT(HRCT)in 37 patients with hearing impairment following trauma from January 1,2018 to July 31,2020,the role of the two inspection methods in the diagnosis of auditory nerve injury was studied.Inclusion criteria were patient had a clear history of trauma and unilateral hearing impairment after trauma;while exclusion criteria were:(1)severe patient with a Glasgow coma scale score<5 because these patients were classified as severe head injury and admitted to the intensive care unit,(2)patient in the subacute stage admitted 72 h after trauma,and(3)patient with prior hearing impairment before trauma.According to Goodman's classification of hearing impairment,the patients were divided into low/medium/severe injury groups.In addition,patients were divided into HRCT-positive and negative groups for further investigation with their BAEP results.The positive rates of BEAP for each group were observed,and the results were analyzed by Chi-square test(p<0.05,regarded as statistical difference).Results:A total of 37 patients were included,including 21 males and 16 females.All of them were hospitalized patients with GCS score of 6-15 at the time of admission.The BAEP positive rate in the medium and severe injury group was 100%,which was significantly higher than that in the low injury group(27.27%)(p<0.01).The rate of BEAP positivity was significantly higher in the HRCT-positive group(20/30,66.7%)than in the HRCT-negative group(1/7,14.3%)(p<0.05).Twenty patients(54.05%)were both positive for BEAP and HRCT test,and considered to have auditory nerve damage.Six patients(16.22%)were both negative for BEAP and HRCT test,and 10 patients(27.03%)were BAEP-negative but HRCT-positive:all the 16 patients were considered as non-neurological injury.The rest 1 case(2.70%)was BAEP-positive but HRCT-negative,which we speculate may have auditory nerve concussion.Conclusion:By way of BAEP combining with skull base HRCT,we may improve the accuracy of the diagnosis of auditory nerve injury.Such a diagnostic strategy may be beneficial to guiding treatment plans and evaluating prognosis.

Neo-intline: integrated pipeline enables neoantigen design through the in-silico presentation of T-cell epitope

Neoantigen vaccines are one of the most effective immunotherapies for personalized tumour treatment.The current immunogen design of neoantigen vaccines is usually based on whole-genome sequencing(WGS)and bioinformatics prediction that focuses on the prediction of binding affinity between peptide and MHC molecules,ignoring other peptide-presenting related steps.This may result in a gap between high prediction accuracy and relatively low clinical effectiveness.In this study,we designed an integrated in-silico pipeline,Neo-intline,which started from the SNPs and indels of the tumour samples to simulate the presentation process of peptides in-vivo through an integrated calculation model.Validation on the benchmark dataset of TESLA and clinically validated neoantigens illustrated that neo-intline could outperform current state-of-the-art tools on both sample level and melanoma level.Furthermore,by taking the mouse melanoma model as an example,we verified the effectiveness of 20 neoantigens,including 10 MHC-I and 10 MHC-II peptides.The in-vitro and in-vivo experiments showed that both peptides predicted by Neo-intline could recruit corresponding CD4^(+)T cells and CD8^(+)T cells to induce a T-cell-mediated cellular immune response.Moreover,although the therapeutic effect of neoantigen vaccines alone is not sufficient,combinations with other specific therapies,such as broad-spectrum immune-enhanced adjuvants of granulocyte-macrophage colony-stimulating factor(GM-CSF)and polyinosinic-polycytidylic acid(poly(I:C)),or immune checkpoint inhibitors,such as PD-1/PD-L1 antibodies,can illustrate significant anticancer effects on melanoma.Neo-intline can be used as a benchmark process for the design and screening of immunogenic targets for neoantigen vaccines.

THE IMPACT OF TROPICAL CYCLONES ON CHINA IN 2015

During 2015 typhoon season(1 January to 15 October), the Northwest Pacifi c and the South China Sea had registered 25 tropical cyclone genesis. 6 of them, including KUJIRA(1508), CHAN-HOM(1509), LINFA(1510), SOUDELOR(1513), DUJUAN(1521) and MUJIGAE(1522), made landfall over China's coastal areas. Despite the high level of activity(the historical average in the same period of 1949-2014 is 21.6), fewer tropical cyclones made landfall over China(the historical average is 6.6). However, these 6 tropical cyclones had an averaged intensity up to 41 m/s, signifi cantly enhanced compared with the multi-year average of 32.8 m/s. The death toll from the 8 tropical cyclones affected China in 2015 is 73. SOUDELOR claimed the most affected population, death toll, missing person, emergency aiding population, damaged home, and MUJIGAE claimed the most direct economic loss. China Meteorological Administration(CMA) mean offi cial track forecast errors in 2015 were smaller than the multi-year means at all forecast times.