Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

Boosting Activity and Selectivity of UiO-66 through Acidity/Alkalinity Functionalization in Dimethyl Carbonate Catalysis.

The acid-base properties of supports have an enormous impact on catalytic reactions to regulate the selectivity and activity of supported catalysts. Herein, a train of Pd-X-UiO-66 (X = NO2 , NH2 , and CH3 ) catalysts with different acidity/alkalinity functional groups and encapsulated Pd(II) species is first developed, whose activities in dimethyl carbonate (DMC) catalysis are then investigated in details. Thereinto, the Pd-NO2 -UiO-66 catalyst with acidity functionalization exhibits the best catalytic behavior: the DMC selectivity stemmed from methyl nitrite (MN) is up to 68%, the conversion of CO is 73.4%. The obtained experimental results demonstrate that the NO2 group not only affected the interaction between X-UiO-66 and Pd(II) active sites but also play an indispensable role in the adsorption and activation of MN and CO, which remarkably promote the formation of the COOCH3 * intermediate and DMC product.

Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy.

BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) account for the majority of cases of monogenetically caused end-stage renal disease (ESRD) in children. Exploring the correlation between the phenotype and genotype of NPHP-RC is helpful for early diagnosis and management. We investigated the phenotype and genotype spectra of NPHP-RC in a Chinese multicentre cohort. METHODS: Crosss-ectional and longitudinal data of 60 patients from 57 families with pathogenic NPHP-RC gene mutations distributed in 22 regions of China were collected into a unified, anonymous database. The mean observation time of this cohort was 3.5±3.1 years. RESULTS: Mutations in NPHP1 and NPHP3 were the most common genetic defects. Overall, 45% of patients presented with isolated nephronophthisis (NPH), and 55% exhibited the extrarenal phenotype, which frequently involved the liver (41.7%, n=25), central nervous system (26.7%, n=16), eyes (26.7%, n=16) and skeletal system (11.7%, n=7). Accidental detection of elevated serum creatinine and non-specific symptoms caused by chronic kidney disease occurred in 65% of patients. Patients carrying NPHP1 mutations mainly presented with isolated NPH (90%, 18/20) and progressed to ESRD at a mean age of 12.9±0.5 years. The mean age of ESRD onset in the non-NPHP1 group was lower than that in the NPHP1 group (6.2±1.4 years, p<0.001), especially for patients carrying NPHP3 mutations (3.1±1.2 years), showing a heterogeneous phenotype characterised by Bardet-Biedl syndrome (12.5%, n=5), Joubert syndrome (7.5%, n=3), COACH syndrome (2.5%, n=1), Mainzer-Saldino syndrome (2.5%, n=1), short-rib thoracic dysplasia (2.5%, n=1) and unclassified symptoms (32.5%, n=13). CONCLUSIONS: The Chinese Children Genetic Kidney Disease Database registry characterised the spectrum of the phenotype and genotype of NPHP-RC in the Chinese population. NPHP1 and NPHP3 were the most common pathogenic genes. Rapid progression to ESRD and liver involvement were noted in patients with NPHP3 mutations.

The novel STAT3 inhibitor WZ-2-033 causes regression of human triple-negative breast cancer and gastric cancer xenografts.

Hyperactive signal transducer and activator of transcription 3 (STAT3) signaling is frequently detected in human triple-negative breast cancer (TNBC) and gastric cancer, leading to uncontrolled tumor growth, resistance to chemotherapy, and poor prognosis. Thus, inhibition of STAT3 signaling is a promising therapeutic approach for both TNBC and gastric cancer, which have high incidences and mortality and limited effective therapeutic approaches. Here, we report a small molecule, WZ-2-033, capable of inhibiting STAT3 activation and dimerization and STAT3-related malignant transformation. We present in vitro evidence from surface plasmon resonance analysis that WZ-2-033 interacts with the STAT3 protein and from confocal imaging that WZ-2-033 disrupts HA-STAT3 and Flag-STAT3 dimerization in intact cells. WZ-2-033 suppresses STAT3-DNA-binding activity but has no effect on STAT5-DNA binding. WZ-2-033 inhibits the phosphorylation and nuclear accumulation of pY705-STAT3 and consequently suppresses STAT3-dependent transcriptional activity and the expression of STAT3 downstream genes. Moreover, WZ-2-033 significantly inhibited the proliferation, colony survival, migration, and invasion of TNBC cells and gastric cancer cells with aberrant STAT3 activation. Furthermore, administration of WZ-2-033 in vivo induced a significant antitumor response in mouse models of TNBC and gastric cancer that correlated with the inhibition of constitutively active STAT3 and the suppression of known STAT3 downstream genes. Thus, our study provides a novel STAT3 inhibitor with significant antitumor activity in human TNBC and gastric cancer harboring persistently active STAT3.

Impact of the COVID-19 pandemic on congenital diaphragmatic hernia patients: a single-center retrospective study.

PURPOSE: To investigate the impact of COVID-19 on the treatment of children with congenital diaphragmatic hernia (CDH). METHODS: We retrospectively collected and compared the data of patients with CDH admitted between January 1, 2020 and December 31, 2021(study group) with the CDH patients admitted before the pandemic between January 1, 2018 and December 31, 2019 (control group). RESULTS: During the pandemic, 41 patients with CDH diagnosed prenatally were transferred to our hospital, and 40 underwent surgical repair. The number of patients treated in our hospital increased by 24.2% compared with the 33 patients before the pandemic. During the pandemic, the overall survival rate, postoperative survival rate and recurrence rate were 85.4%, 87.5% and 7.3%, respectively, and there were no significant differences compared with the control group (75.8%, 83.3% and 9.1%, respectively). The average length of hospital stay in patients admitted during the pandemic was longer than that in the control group (31 days vs. 16 days, P < 0.001), and the incidence of nosocomial infection was higher than that in the control group (19.5% vs. 3%, P = 0.037). CONCLUSIONS: CDH patients confirmed to be SARS-CoV-2 infection-free can receive routine treatment. Our data indicate that the implementation of protective measures during the COVID-19 pandemic, along with appropriate screening and case evaluation, do not have a negative impact on the prognosis of children.

Multicenter study of the clinical features and mutation gene spectrum of Chinese children with Dent disease.

Dent disease is a rare X-linked recessive inherited tubular disease. In this multicenter study, the clinical presentation and genetic background of Chinese children with Dent disease are studied to improve the cognition and diagnostic ability of pediatricians. In this prospective cohort, we described the genotype and phenotype of a national cohort composed of 45 pediatric probands with Dent disease belonging to 45 families from 12 different regions of China recruited from 2014 to 2018 by building up the multicenter registration system. The CLCN5 gene from 32 affected families revealed 28 different mutations. The OCRL gene from 13 affected families revealed 13 different mutations. The incidence of low-molecular-weight proteinuria (LMWP) in both Dent disease type 1 populations and Dent disease type 2 populations was 100.0%; however, the incidence of other manifestations was not high, which was similar to previously reported data. Therefore, LMWP is a key clinical feature that should alert clinicians to the possibility of Dent disease. A high amount of LMWP combined with positive gene test results can be used as the diagnostic criteria for this disease. The diagnostic criteria are helpful in reducing the missed diagnosis of this disease and are beneficial for protecting the renal function of these patients through early diagnosis and early intervention.

[Clinical features and TTC21B genotype of a child with nephronophthisis type 12].

Nephronophthisis (NPHP) is a group of autosomal recessive tubulointerstitial cystic kidney disorders. This article reports a case of NPHP type 12 caused by TTC21B mutations. The girl had an insidious onset, with moderate proteinuria, renal dysfunction, stage 2 hypertension, situs inversus, and short phalanges when she visited the hospital for the first time at the age of 3 years and 6 months. The renal lesions progressed to end-stage renal disease (ESRD) before she was 4 years old. Urine protein electrophoresis showed glomerular proteinuria. There were significant increases in urinary ß2-microglobulin and α1-microglobulin. Gene detection revealed two compound heterozygous mutations, c.1552T>C (p.C518R) and c.752T>G (p.M251R), in the TTC21B gene, which came from her father and mother respectively. The c.752T>G mutation was a novel mutation. It is concluded that besides typical tubular changes of NPHP, marked glomerular damage is also observed in patients with TTC21B gene mutations.

Advances of recurrent risk factors and management of choledocholithiasis.

Gallstone disease is a common and frequently occurring disease in human, and it is the main disease among the digestive system diseases. The incidence of gallstone disease in western countries is about 5%-22%, and common bile duct stones (CBDS) accounts for 8%-20%. CBDS easily lead to biliary obstruction, secondary cholangitis, pancreatitis, and obstructive jaundice, even endanger life. Therefore, it needs timely treatment once diagnosed. The recurrence of choledocholithiasis after bile duct stones clearance involves complicated factors and cannot be completely elaborated by a single factor. The risk factors for recurrence of choledocholithiasis include bacteria, biliary structure, endoscopic and surgical treatment, and inflammation. The modalities for management of choledocholithiasis are endoscopic retrograde cholangiopancreatography (ERCP), laparoscopic or open common bile duct exploration, dissolving solutions, extracorporeal shockwave lithotripsy (ESWL), percutaneous radiological interventions, electrohydraulic lithotripsy (EHL) and laser lithotripsy. We compare the different benefits between surgery and ERCP. And finally, we make a summary of the current strategy for reducing the recurrence of CBDS and future perspectives for CBDS management.

Molecular identification and expression analysis of TLR5M and TLR5S from orange-spotted grouper (Epinepheluscoioides).

Toll-like receptor 5 (TLR5) is an important receptor that interacts with bacterial flagellin and regulates host immune response in mammal. Recent studies demonstrate that piscine contains two types of TLR5, namely membrane form of TLR5 (TLR5M) and soluble form of TLR5 (TLR5S), and both of which perform crucial role in flagellin response. In the present study, a TLR5M and a TLR5S sequence was cloned from orange-spotted grouper (Epinepheluscoioides), and their ORFs are respectively 2466 bp (821 aas) and 1935 bp (644 aas). EcTLR5M has the typical TLR structure of a LRR domain, a transmembrane region and a TIR domain, while EcTLR5S only contains a LRR domain like other species' TLR5S. Both molecules have 23 LRR motifs, a LRR-NT and a LRR-CT in the LRR domain, similar to those of other species. Phylogenetic and sequence alignment indicated that both EcTLR5s respectively displayed closer relationship and higher sequence identity with those in other fish species. In healthy grouper, EcTLR5M was highly expressed in the skin, head kidney and spleen, while EcTLR5S was mainly detected in the liver. Ciliate Cryptocaryon irritans infection could significantly up-regulate the expression level of EcTLR5s in the gill and spleen from day 1 to day 3, and higher expression fold change was observed in the spleen. Taken together, the present studies contributed to understanding the function of piscine TLR5M/S and clarify their possible role in fish immune response against ciliate infection.

Electrochemical Synthesis of Benzazoles from Alcohols and o-Substituted Anilines with a Catalytic Amount of Co(II) Salt.

An electrochemical synthesis of benzazoles directly from alcohols and o-substituted anilines has been developed. The reaction conditions have been optimized by varying the composition of the electrolyte and the metal salt used as catalyst. The cyclization proceeds smoothly with a catalytic amount of a cobalt salt under air at room temperature to afford 2-substituted benzimidazoles, benzothiazoles, and benzoxazoles in good to excellent yields with a wide substrate scope.

[Clinical and genetic analysis of Dent disease in 4 Chinese children].

OBJECTIVE: To study the clinical features and gene mutations of 4 Chinese children with Dent disease. METHODS: The clinical and laboratory data of 4 children with Dent disease were analyzed retrospectively. Genetic testing of the 4 cases was carried out. RESULTS: All of 4 cases were boys. The first impression of Cases 1-3 was Fanconi syndrome. Proteinuria was presented as the first impression in Case 4. All 4 boys presented with low-molecular weight proteinuria (LMWP) and hypercalciuria, including 3 cases with hematuria, 1 case with kidney stones, 2 cases with nephrocalcinosis, 3 cases with hypophosphatemia, and 3 cases with rickets. Mutations of the CLCN5 gene were revealed in three patients (Cases 1, 2 and 4), including exon 6-7del, c.785_787de l(p.263del Leu) and c.1039 C>T (p.Arg347Term). The first two gene mutations had never reported before. CONCLUSIONS: Urine protein electrophoresis should be carried out for patients with proteinuria. Dent disease should be taken into consideration when patients with Fanconi syndrome have hypercalciuria, nephrocalcinosis or kindey stones. Genetic analyses are needed for a definite diagnosis.

The mechanism of enterohepatic circulation in the formation of gallstone disease.

Bile acids entering into enterohepatic circulating are primary acids synthesized from cholesterol in hepatocyte. They are secreted actively across canalicular membrane and carried in bile to gallbladder, where they are concentrated during digestion. About 95% BAs are actively taken up from the lumen of terminal ileum efficiently, leaving only approximately 5% (or approximately 0.5 g/d) in colon, and a fraction of bile acids are passively reabsorbed after a series of modifications in the human large intestine including deconjugation and oxidation of hydroxy groups. Bile salts hydrolysis and hydroxy group dehydrogenation reactions are performed by a broad spectrum of intestinal anaerobic bacteria. Next, hepatocyte reabsorbs bile acids from sinusoidal blood, which are carried to liver through portal vein via a series of transporters. Bile acids (BAs) transporters are critical for maintenance of the enterohepatic BAs circulation, where BAs exert their multiple physiological functions including stimulation of bile flow, intestinal absorption of lipophilic nutrients, solubilization, and excretion of cholesterol. Tight regulation of BA transporters via nuclear receptors (NRs) is necessary to maintain proper BA homeostasis. In conclusion, disturbances of enterohepatic circulation may account for pathogenesis of gallstones diseases, including BAs transporters and their regulatory NRs and the metabolism of intestinal bacterias, etc.

MDM2 SNP309T>G polymorphism and hepatocellular carcinoma risk: a meta-analysis.

Case-control studies on the association between mouse double-minute 2 homolog (MDM2) SNP309T>G polymorphism and hepatocellular carcinoma have provided either controversial or inconclusive results. To clarify the effect of MDM2 SNP309T>G polymorphism on the risk of hepatocellular carcinoma, a meta-analysis of all case-control observational studies was performed. Pooled odds ratios (ORs) for various polymorphisms were estimated using random and fixed effects models. The Q-statistic was used to evaluate the homogeneity, and Egger and Begg tests were used to assess publication bias. Overall, the MDM2 SNP309T>G polymorphism was associated with a risk of hepatocellular carcinoma (OR = 0.68; 95% CI = 0.54-0.85 for allele contrast, p = 0.0005, phet = 0.004). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast. In the analysis stratified by ethnicity, significant associations were found in the Caucasian population in all of the genetic models. In addition, heterogeneity disappeared in subgroups of Caucasian subjects. Our pooled data suggest evidence for a major role of MDM2 SNP309T>G polymorphism in the carcinogenesis of hepatocellular carcinoma, especially among Caucasian populations.

Rapid detection and differentiation of Clonorchis sinensis and Opisthorchis viverrini using real-time PCR and high resolution melting analysis.

Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne pathogens, causing serious public health problem in Asia. The present study developed an assay integrating real-time PCR and high resolution melting (HRM) analysis for the specific detection and rapid identification of C. sinensis and O. viverrini. Primers targeting COX1 gene were highly specific for these liver flukes, as evidenced by the negative amplification of closely related trematodes. Assays using genomic DNA extracted from the two flukes yielded specific amplification and their identity was confirmed by sequencing, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit below 1 pg of purified genomic DNA, 5 EPG, or 1 metacercaria of C. sinensis. Moreover, C. sinensis and O. viverrini were able to be differentiated by their HRM profiles. The method can reduce labor of microscopic examination and the contamination of agarose electrophoresis. Moreover, it can differentiate these two flukes which are difficult to be distinguished using other methods. The established method provides an alternative tool for rapid, simple, and duplex detection of C. sinensis and O. viverrini.

A novel modified polydopamine based on melanin-like materials for antibacterial, hydrophobic, and ultraviolet protective of textiles.

The development of environmentally friendly multifunctional auxiliaries for textile modification is the focus of attention in textile industry in recent years. Polydopamine is an important biological macromolecule and widely used in biomedicine, nanomaterials, material surface modification and other fields. In this study, the novel multifunctional melanin-like nanoparticles (Nha-PDA NPs) were prepared and used for antibacterial, hydrophobic, and UV protective of textiles. Nha-PDA NPs were prepared with dopamine (DA) and n-hexylamine (Nha) by simple autoxidation copolymerization. Nha-PDA NPs were bound to the fabric surface through the PDA structure in Nha-PDA NPs that has been widely confirmed to have strong adhesion on the surface of many materials. The modified fabrics, Nha-PDA NPs@Cotton, had good hydrophobic, antibacterial and UV protective properties. The static water contact angles of the modified fabrics could reach 120°. The antibacterial rates of Nha-PDA NPs@Cotton against E. coli and S. aureus were above 85 %. The maximum UPF value of the modified cotton was 362, indicating that the ultraviolet protection performance was excellent. The fabric modified with multifunctional melanin-like nanoparticle provides a green way for the multifunctional modification of textiles.

Phenotype of Takayasu-like vasculitis and cardiopathy in patients with Blau syndrome.

OBJECTIVES: We aimed to determine the prevalence of cardiovascular involvement in our Blau syndrome (BS) cohort and provide detailed analysis of their cardiovascular manifestations and outcome. We also tried to find out the risk factors for developing cardiovascular involvement. METHODS: Clinical manifestations, laboratory findings, and treatments were reviewed. Clinical features were compared between children with cardiovascular involvement and those without angiocardiopathy. RESULTS: A total of 38 BS children were eligible for final analysis. Among them, 13 (34.2%) developed Takayasu-like vasculitis and/or cardiopathy. Compared with those without angiocardiopathy, recurrent fever was more frequent in BS patients with cardiovascular involvement (p < 0.001). What is more, tumor necrosis factor alpha antagonists (anti-TNF) were more urgently needed in children with cardiovascular involvement (p = 0.015). BS patients with cardiovascular involvement include 4 with Takayasu-like vasculitis and 9 with cardiopathy. The onset of cardiovascular manifestations ranged from 0.75 to 18.5 years of age, with most cases occurring before school period. Symptoms were elusive and lacked specificity, such as dizziness, short of breath, and edema. Some patients were even identified because of the unexpected hypertension during follow-up. Cardiopathy and vasculitis occurred in patients with different genotypes. Imaging changes were discovered before the presentation of the typical triad in 3/4 patients with Takayasu-like vasculitis. Three children developed left ventricular dysfunction with decreased left ventricular ejection fraction. Combination of glucocorticoids and methotrexate with anti-TNF agents is a common treatment option for these BS patients. In the cohort, BS-related cardiovascular involvement was controlled well, with cardiac structural and functional abnormalities completely recovered and slower progression of vasculitis lesions. CONCLUSION: Cardiovascular manifestations is not rare in BS patients. Because of its insidious onset, a systematic and comprehensive assessment of cardiovascular involvement should be performed in newly diagnosed patients with BS. Aggressive initiation of anti-TNF agents may be beneficial to improve the prognosis. Key Points • About 34.2% patients with Blau syndrome developed Takayasu-like vasculitis and/or cardiopathy. • Compared with those without angiocardiopathy, recurrent fever and application of anti-TNF agents were more frequent in BS patients with cardiovascular involvement (p < 0.001, p = 0.015) • Regular assessment of cardiovascular involvement is extremely necessary because of its insidious onset.

Distribution of pathogenic bacteria and antimicrobial sensitivity of eye infections in Suzhou.

AIM: To investigate the types of bacteria in patients with eye infections in Suzhou and their drug resistance to commonly used antibacterial drugs. METHODS: The clinical data of 155 patients were retrospectively collected in this study, and the pathogenic bacteria species and drug resistance of each pathogenic bacteria were analyzed. RESULTS: Among the 155 patients (age from 12 to 87 years old, with an average age of 57, 99 males and 56 females) with eye infections (160 eyes: 74 in the left eye, 76 in the right eye and 5 in both eyes, all of which were exogenous), 71 (45.81%) strains were gram-positive bacteria, 23 (14.84%) strains were gram-negative bacteria and 61 (39.35%) strains were fungi. Gram-positive bacteria were highly resistant to penicillin and erythromycin (78.87% and 46.48% respectively), but least resistant to vancomycin at 0. Gram-negative bacteria were highly resistant to cefoxitin and compound sulfamethoxazole (100% and 95.65% respectively), but least resistant to meropenem at 0. Comparison of the resistance of gram-positive and gram-negative bacteria to some drugs revealed statistically significant differences (P<0.05) in the resistance of both to cefoxitin, cotrimoxazole, levofloxacin, cefuroxime, ceftriaxone and ceftazidime, and both had higher rates of resistance to gram-negative bacteria than to gram-positive bacteria. The distribution of bacterial infection strains showed that Staphylococcus epidermidis was the most common strain in the conjunctiva, cornea, aqueous humor or vitreous body and other eye parts. Besides, Fusarium and Pseudomonas aeruginosa were also among the most common strains of conjunctival and corneal infections. CONCLUSION: Gram-positive bacteria are the dominant bacteria in eye infections, followed by gram-negative bacteria and fungi. Considering the resistance of gram-negative bacteria to multiple drugs, monitoring of bacteria should be strengthened in eye bacterial infections for effective prevention and control to reduce complications caused by eye infections.

Proteomic analysis of serum extracellular vesicles from biliary tract infection patients to identify novel biomarkers.

Biliary tract infection (BTI), a commonly occurring abdominal disease, despite being extensively studied for its initiation and underlying mechanisms, continues to pose a challenge in the quest for identifying specific diagnostic biomarkers. Extracellular vesicles (EVs), which emanate from diverse cell types, serve as minute biological entities that mirror unique physiological or pathological conditions. Despite their potential, there has been a relatively restricted exploration of EV-oriented methodologies for diagnosing BTI. To uncover potent protein biomarkers for BTI patients, we applied a label-free quantitative proteomic method known for its unbiased and high-throughput nature. Furthermore, 192 differentially expressed proteins surfaced within EVs isolated from individuals afflicted with BTI. Subsequent GO and KEGG analyses pinpointed Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and Crumbs homolog 3 (CRB3) as noteworthy biomarkers. Validation via data analysis of plasma-derived EV samples confirmed their specificity to BTI. Our study leveraged an unbiased proteomic tool to unveil CEACAM1 and CRB3 as promising protein biomarkers in serum EVs, presenting potential avenues for the advancement of diagnostic systems for BTI detection.

Red-emitting upconverting nanoparticles for photodynamic therapy in cancer cells under near-infrared excitation.

Upconverting nanoparticles (UCNPs) have attracted considerable attention as potential photosensitizer carriers for photodynamic therapy (PDT) in deep tissues. In this work, a new and efficient NIR photosensitizing nanoplatform for PDT based on red-emitting UCNPs is designed. The red emission band matches well with the efficient absorption bands of the widely used commercially available photosensitizers (Ps), benefiting the fluorescence resonance energy transfer (FRET) from UCNPs to the attached photosensitizers and thus efficiently activating them to generate cytotoxic singlet oxygen. Three commonly used photosensitizers, including chlorine e6 (Ce6), zinc phthalocyanine (ZnPc) and methylene blue (MB), are loaded onto the alpha-cyclodextrin-modified UCNPs to form Ps@UCNPs complexes that efficiently produce singlet oxygen to kill cancer cells under 980 nm near-infrared excitation. Moreover, two different kinds of drugs are co-loaded onto these nanoparticles: chemotherapy drug doxorubicin and PDT agent Ce6. The combinational therapy based on doxorubicin (DOX)-induced chemotherapy and Ce6-triggered PDT exhibits higher therapeutic efficacy relative to the individual means for cancer therapy in vitro.

Electrochemical technique and copper-promoted transformations: selective hydroxylation and amination of arylboronic acids.

An efficient and selective electrosynthesis of phenols and anilines from arylboronic acids in aqueous ammonia is achieved in an undivided cell. By simply changing the concentration of aqueous ammonia and the anode potential, good yields of phenols and anilines can be obtained chemoselectively with high reaction rates. We propose that anodic oxidation could have played an important role in these transformations.