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Ru(II) complexes were synthesized with π-expanding (phenyl, fluorenyl, phenanthrenyl, naphthalen-1-yl, naphthalene-2-yl, anthryl, and pyrenyl groups) attached at a 1H-imidazo[4,5-f][1,10]phenanthroline ligand and 4,4′-dimethyl-2,2′-bipyridine (4,4′-dmb) co-ligands. These Ru(II) complexes were characterized by 1D and 2D NMR, and mass spectroscopy, and studied for visible-light and dark toxicity to human malignant melanoma SK-MEL-28 cells. In the SKMEL-28 cells, the Ru(II) complexes are highly phototoxic (EC(50) = 0.2–0.5 μM), and have low dark toxicity (EC(50) = 58–230 μM). The highest phototherapeutic index (PI) of the series was found with the Ru(II) complex bearing the 2-(pyren-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline ligand. This high PI is in part attributed to the π-rich character added by the pyrenyl group, and a possible low-lying and longer-lived (3)IL state due to equilibration with the (3)MLCT state. While this pyrenyl Ru(II) complex possessed a relatively high quantum yield for singlet oxygen formation (Φ(Δ) = 0.84), contributions from type-I processes (oxygen radicals and radical ions) are competitive with the type-II ((1)O(2)) process based on effects of added sodium azide and solvent deuteration.

// Jing Zhang 1, * , Nan Luo 1, * , Yu Tian 2, * , Jiazhi Li 3 , Xiaozhou Yang 1 , Huimin Yin 1 , Congshu Xiao 1 , Jie Sheng 4 , Yang Li 1 , Bo Tang 1 , Rongkuan Li 1 1 Department of Infection, The Second Hospital of Dalian Medical University, Dalian, Liaoning, P.R. China 2 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning, P.R. China 3 Department of Pathology, Dalian Medical University, Dalian, Liaoning, P.R. China 4 Department of Urology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, P.R. China * These authors contributed equally to this work Correspondence to: Bo Tang, email: dytangbo @163.com Rongkuan Li, email: dalianlrk@126.com Yang Li, email: 805707550@qq.com Keywords: USP22, liver neoplasms, chemoresistance, Smad4, Akt Received: May 17, 2016 Accepted: February 13, 2017 Published: March 01, 2017 ABSTRACT USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in chemoresistant HCC tissues and cells and was correlated with the prognosis of HCC patients who received chemotherapy. Silencing USP22 in chemoresistant HCC Bel/Fu cells dramatically inhibited proliferation, migration, invasion and epithelial-mesenchymal transition in vitro ; suppressed tumorigenic and metastatic capacities in vivo ; and inhibited drug resistance-related proteins (MDR1, LRP, MRP1). Mechanistically, we found that USP22 knockdown exerts its function through down-regulating PI3K and activating Smad4, which inhibited phosphorylation of Akt. Silencing Smad4 blocked USP22 knockdown-induced Akt inhibition in Bel/Fu cells. Our results, for the first time, provide evidence that USP22 plays a critical role in the development of chemoresistant HCC cells and that high USP22 expression serves as a molecular marker for the prognosis of HCC patients who undergo chemotherapy.

Five heteroleptic cationic iridium complexes with a π-expansive cyclometalating 2,3-diphenylbenzo[g]quinoxaline (dpbq) ligand (C^N ligand) and different diimine ligands (N^N ligands) (i.e. 2,2′-bipyridine (bpy, 1), phenanthroline (phen, 2), 2-(2-pyridinyl)quinoline (pqu, 3), 2,2′-bisquinoline (bqu, 4), and 2-(quinolin-2-yl)quinoxaline (quqo, 5)) were synthesized and characterized. The lowest-energy singlet electronic transitions (S1 states) were mainly dpbq ligand-centred 1ILCT (intraligand charge transfer)/1MLCT (metal to ligand charge transfer) transitions mixed with some 1π,π* transitions for complexes 1–4 with increased contributions from 1LLCT (ligand to ligand charge transfer) in 3 and 4. For complex 5, the S1 state was switched to the 1LLCT/1MLCT transitions. All five complexes displayed weak near-infrared (NIR) phosphorescence, with maximal emission output spanning 700–1400 nm and quantum yields being on the order of 10−3. The triplet state absorptions of 1–4 all resembled that of the [Ir(dpbq)2Cl]2 dimer with lifetimes of ca. 400 ns, while the TA spectrum of 5 possessed the characteristics of both the quqo ligand and the [Ir(dpbq)2Cl]2 dimer with a bi-exponential decay of ca. 5 μs and 400 ns. While the photophysics of these complexes differ slightly, their theranostic photodynamic therapy (PDT) effects varied drastically. All of the complexes were biologically active toward melanoma cells. Complexes 2 and 3 were the most cytotoxic, with 230–340 nM activity and selectivity factors for melanoma cells over normal skin fibroblasts of 34 to 40 fold. Complexes 2, 3, and 5 became very potent cytotoxins with light activation, with EC50 values as low as 12–18 nM. This potent nanomolar light-triggered activity combined with a lower dark toxicity resulted in 5 having a phototherapeutic index (PI) margin of almost 275. The bpy coligand led to the least amount of dark toxicity of 1, while phen and pqu produced cytotoxic but selective complexes 2 and 3. The quqo coligand produced the most potent complex 5 for in vitro PDT, both in terms of photocytotoxicity and PI. All Ir(III) complexes exhibited very bright NIR phosphorescence in melanoma cells. The wide range of cytotoxicity and photocytotoxicity effects within a relatively small class of complexes highlights the importance of the identity of the coligand in the biological activity of the π-expansive biscyclometalated Ir(III) complexes, and their bright NIR emission in live cells demonstrates their potential as theranostic PDT agents.

A new family of cyclometalated ruthenium(II) complexes [Ru(N^N)(2) (C^N)](+) derived from the π-extended benzo[h]imidazo[4,5-f]quinolone ligand appended with thienyl groups (n=1–4, compounds 1–4) was prepared and characterized for their chemical, photophysical, and photobiological properties. The lipophilicities of 1–4, determined as octanol-water partition coefficients (log P(o/w)), were positive and increased with the number of thienyl units. The absorption and emission bands of the C^N compounds were red-shifted by up to 200 nm relative to the analogous Ru(II) diimine systems. All of the complexes exhibited dual emission, with the intraligand fluorescence ((1)IL, C^N-based) shifting to lower energies with increasing n and the metal-to-ligand charge transfer phosphorescence ((3)MLCT, N^N-based) remaining unchanged. Compounds 1–3 exhibited excited state absorption (ESA) profiles consistent with lowest-lying (3)MLCT states when probed by nanosecond transient absorption (TA) spectroscopy with 532-nm excitation, and had contributions from (1)IL(C^N) states with 355-nm excitation. These assignments were supported by the lifetimes observed (300 µM); 1–3 were cytotoxic and yielded EC(50) values between 1–20 µM. The photocytotoxicites with visible light ranged from 87 nM with a phototherapeutic index (PI) of 13 for 1 to approximately 1 µM (PI = >267) for 4. With red light, EC(50) values varied from 270 nM (PI=21) for 3 to 12 µM for 4 (PI = >25). The larger PIs for 4, especially with visible light, were attributed to the much lower dark cytotoxicity for this compound. Since the dark cytotoxicity contributes substantially to the observed photocytotoxicity for 1–3, it was not possible to assess whether the (3)IL state of 4 led to a much more potent phototoxic mechanism in the absence of dark toxicity. There was no stark contrast in cellular uptake and accumulation by laser scanning confocal and differential interference contrast (DIC) microscopy to explain the large differences in dark toxicities between 1–3 and 4. Nevertheless, the study highlights a new family of Ru(II) C^N complexes where π-conjugation beyond a certain point results in low dark cytotoxicity with high photocytotoxicity, opposing the notion that cyclometalated Ru(II) systems are too toxic to be phototherapeutic agents.

This study investigates the correlation between photocytotoxicity and the prolonged excited state lifetimes exhibited by certain Ru(II) polypyridyl photosensitizers comprised of π-expansive ligands. The eight metal complexes selected for this study differ markedly in their triplet state configurations and lifetimes. Human melanoma SKMEL28 and human leukemia HL60 cells were used as in vitro models to test photocytotoxicity induced by the compounds when activated by either broadband visible or monochromatic red light. The photocytotoxicities of the metal complexes investigated varied over two orders of magnitude and were positively correlated with their excited state lifetimes. The complexes with the longest excited state lifetimes, contributed by low-lying (3)IL states, were the most phototoxic toward cancer cells under all conditions.

A series of cationic heteroleptic iridium(III) complexes bearing tris-diimine ligands [Ir(phen)(2)(R-phen)](3+) (R-phen = phenanthroline (1), 3,8-diphenylphenanthroline (2), 3,8-dipyrenylphenanthroline (3), 3-phenylphenanthroline (4), 3-pyrenylphenanthroline (5), and 3,8-diphenylethynylphenanthroline (6)) were synthesized and characterized. These complexes possessed phen ligand-localized (1)π,π* transitions below 300 nm, and charge transfer ((1)CT) and/or (1)π,π* transitions between 300 and 520 nm. In 1, 2, 4, and 6, the low-energy bands were mixed (1)CT/(1)π,π*. However, the increased π-donating ability of the pyrenyl substituent(s) in 3 and 5 split the low-energy bands into a pyrene-based (1)π,π* transition at 300-380 nm and an intraligand charge transfer ((1)ILCT) transition at 380-520 nm. All complexes were emissive at room temperature in CH(3)CN, but the parentage of the emitting state varied depending on the R substituent(s). Complex 1 exhibited predominantly phen ligand-localized (3)π,π* emission mixed with metal-to-ligand charge transfer ((3)MLCT) character, while the emission of 2, 4, and 6 was predominantly from the excited-state with (3)π,π*/(3)ILCT/(3)MLCT character. The emission from 3 and 5 was dominated by pyrene-based (3)π,π* states mixed with (3)ILCT character. The different natures of the lowest triplet excited states were also reflected by the different spectral features and lifetimes of the triplet transient absorption of these complexes. Complexes 3 and 5 had singlet oxygen quantum yields as high as 81 and 72%, respectively. Both gave submicromolar phototoxicities toward cancer cells (SK-MEL-28 human melanoma) and bacteria (S. aureus and S. mutans) with visible light activation (and marginal to no photobiological activity with red light). Their visible-light phototherapeutic indices (PIs) toward SK-MEL-28 cells were 248 for 3 and >435 for 5; PIs were lower in bacteria (≤62) due to their inherent antimicrobial activities. Both complexes were shown to produce substantial amounts of intracellular reactive oxygen species (ROS), which may account for their photobiological activities.

Transition metal complexes are of increasing interest as photosensitizers in photodynamic therapy (PDT) and, more recently, for photochemotherapy (PCT). In recent years, Ru (II) polypyridyl complexes have emerged as the most widely studied systems for both PDT and PCT. Their rich photochemical and photophysical properties derive from a variety of excited-state electronic configurations accessible with visible and near-infrared light, and these properties can be exploited for both energy- and electron-transfer processes that can yield highly potent oxygen-dependent and/or oxygen-independent photobiological activity. Selected examples highlight the use of rational design in coordination chemistry to control the lowest-energy triplet excited state configurations for eliciting a particular type of photoreactivity for PDT and/or PCT effects. These principles are also discussed in the context of the development of TLD1433, the first Ru(II)-based photosensitizer for PDT to enter a human clinical trial. The design of TLD1433 arose from a tumor-centered approach, as part of a complete PDT package that included the light component and the protocol for treating nonmuscle invasive bladder cancer. Briefly, this review summarizes the challenges to bringing PDT into mainstream cancer therapy. It considers the chemical and photophysical solutions that transition metal complexes offer, and it puts into context the multidisciplinary effort needed to bring a new drug to clinical trial.

A series of cationic dinuclear iridium(III) complexes (Ir1 - Ir5) bearing terpyridine-capped fluorenyl bridging ligand and different polypyridyl or cyclometalating terminal tridentate ligands were synthesized, characterized, and evaluated for their photophysical and photobiological activities. The influence of the bridging and terminal ligands on the photophysical properties of the complexes was investigated by UV-vis absorption, emission, and transient absorption spectroscopy, and simulated by TDDFT calculations. All of the complexes displayed strong bridging-ligand localized visible (1)π,π* absorption and red- or near-infrared (NIR) phosphorescence as well as broad triplet excited-state absorption across both visible and NIR wavelengths. These triplet states were assigned as predominantly (3)π,π* for Ir1 (τ = 3.1 μs) and Ir4 (τ = 48 μs), and predominantly (3)CT (charge transfer) for Ir2, Ir3 and Ir5 (τ = 1.7–2.7 μs). Complexes Ir1 – Ir5 acted as in vitro photodynamic therapy (PDT) agents toward human SK-MEL-28 melanoma cells when activated with visible light, with submicromolar photocytotoxicity and phototherapeutic indices (PIs) ranging from 20 to almost 300. The in vitro PDT effects with visible light did not correlate with singlet oxygen ((1)O(2)) quantum yields or DNA photocleaving capacity probed under cell-free conditions. All of the Ir(III) complexes phosphoresced brightly when associated with compromised cells (with or without a light treatment) and exhibited photoactivated cellular uptake, highlighting the theranostic potential of this new class of Ir(III) complex photosensitizers.

The photophysical and photobiological properties of a new class of cyclometalated ruthenium(II) compounds incorporating π-extended benzo[h]imidazo[4,5-f]quinoline (IBQ) cyclometalating ligands (C^N) bearing thienyl rings (n=1–4, compounds 1–4) were investigated. Their octanol-water partition coefficients (log P(o/w)) were positive, and increased with n. Their absorption and emission energies were red-shifted substantially compared to the analogous Ru(II) diimine (N^N) complexes. They displayed C^N-based intraligand (IL) fluorescence and triplet excited-state absorption that shifted to longer wavelengths with increasing n, and N^N-based metal-to-ligand charge transfer (MLCT) phosphorescence that was independent of n. Their photoluminescence lifetimes (τ(em)) ranged from 4–10 ns for (1)IL states and 12–18 ns for (3)MLCT states. Transient absorption lifetimes (τ(TA)) were 5–8 μs with 355-nm excitation, ascribed to (3)IL states that became inaccessible for 1–3 with 532-nm excitation (1–3, τ(TA)=16–17 ns); the (3)IL of 4 only was accessible by lower energy excitation, τ(TA)=3.8 μs. Complex 4 was nontoxic (EC(50) >300 μM) to SK-MEL-28 melanoma cells and CCD1064-Sk normal skin fibroblasts in the dark, while 3 was selectively cytotoxic to melanoma (EC(50)= 5.1 μM) only. Compounds 1 and 2 were selective for melanoma cells in the dark, with submicromolar potencies (EC(50)=350–500 nM) and selectivity factors (SFs) around 50. The photocytotoxicities of compounds 1–4 toward melanoma cells were similar, but only compounds 3 and 4 displayed significant phototherapeutic indices (PIs) (3, 43; 4, >1,100). The larger cytotoxicities for compounds 1 and 2 were attributed to increased cellular uptake and nuclear accumulation, and possibly related to the DNA-aggregating properties of all four compounds as demonstrated by cell-free gel mobility-shift assays. Together, these results demonstrate a new class of thiophene-containing Ru(II) cyclometalated compounds that contain both highly selective chemotherapeutic agents and extremely potent photocytotoxic agents.

Five heteroleptic tris-diimine ruthenium(II) complexes [RuL(N^N)2](PF6)2 (where L is 3,8-di(benzothiazolylfluorenyl)-1,10-phenanthroline and N^N is 2,2′-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), 1,4,8,9-tetraazatriphenylene (tatp) (3), dipyrido[3,2-a:2′,3′-c]phenazine (dppz) (4), or benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine (dppn) (5), respectively) were synthesized. The influence of π-conjugation of the ancillary ligands (N^N) on the photophysical properties of the complexes was investigated by spectroscopic methods and simulated by density functional theory (DFT) and time-dependent DFT. Their ground-state absorption spectra were characterized by intense absorption bands below 350 nm (ligand L localized 1π,π* transitions) and a featureless band centered at ∼410 nm (intraligand charge transfer (1ILCT)/1π,π* transitions with minor contribution from metal-to-ligand charge transfer (1MLCT) transition). For complexes 4 and 5 with dppz and dppn ligands, respectively, broad but very weak absorption (...

Combining the best attributes of organic photosensitizers with those of coordination complexes is an elegant way to achieve prolonged excited state lifetimes in Ru(II) dyads. Not only do their reduced radiative and nonradiative rates provide ample time for photosensitization of reactive oxygen species at low oxygen tension but they also harness the unique properties of (3)IL states that can act as discrete units or in concert with (3)MLCT states. The imidazo[4,5-f][1,10]phenanthroline framework provides a convenient tether for linking π-expansive ligands such as pyrene to a Ru(II) scaffold, and the stabilizing coligands can fine-tune the chemical and biological properties of these bichromophoric systems. The resulting dyads described in this study exhibited nanomolar light cytotoxicities against cancer cells with photocytotoxicity indices exceeding 400 for some coligands employed. This potency extended to bacteria, where concentrations as low as 10 nM destroyed 75% of a bacterial population. Notably, these dyads remained extremely active against biofilm with light photocytotoxicities against these more resistant bacterial populations in the 10-100 nM regime. The results from this study demonstrate the versatility of these highly potent photosensitizers in destroying both cancer and bacterial cells and expand the scope of compounds that utilize low-lying (3)IL states for photobiological applications.

Small-molecule fluorescent reporters of disease states are highly sought after, yet they remain elusive. Anthranilic acids are extremely sensitive environmental probes, and hold promise as general but selective agents for cancer-cell detection if they can be equipped with the appropriate targeting groups. The optical properties of a small library of N-isopropyl invariant anthranilic acids were investigated in methanol and chloroform. Points of variation included: fluoro, trifluoromethyl, or cyano substitution on the aromatic ring, and derivitization of the parent carboxylic acid as esters or secondary carboxamides. Phenylboronic acid conjugation at the carboxylic acid alongside un-, mono-, and dimethylated 2-amino groups was also explored. The boron-containing anthranilic acids were also evaluated as sensitive fluorescent probes for cancer cells using laser scanning confocal microscopy. In general, the compounds produced blue fluorescence that was strongly influenced by substitution and environment. 4-Trifluoromethyl and 4-cyano esters proved to be the most sensitive environmental probes with quantum yields as large as 100% in chloroform, and enhancements of up to 30-fold on going from methanol to chloroform. Stokes shifts ranged from 63 to 120 nm, generally increasing with ortho-substitution and environmental polarity. It was demonstrated that phenylboronic acid conjugation was an attractive method for cancer cell detection via boronate ester formation with overexpressed glycoproteins (with no interference from normal, healthy cells), presumably due to favorable boron-sialic acid interactions.

Members of a family of Ru(II)-appended pyrenylethynylene dyads were synthesized, characterized according to their photophysical and photobiological properties, and evaluated for their collective potential as photosensitizers for metal-organic photodynamic therapy. The dyads in this series possess lowest-lying (3)IL-based excited states with lifetimes that can be tuned from 22 to 270 μs in fluid solution and from 44 to 3440 μs in glass at 77 K. To our knowledge, these excited-state lifetimes are the longest reported for Ru(II)-based dyads containing only one organic chromophore and lacking terminal diimine groups. These excited states proved to be extremely sensitive to trace amounts of oxygen, owing to their long lifetimes and very low radiative rates. Herein, we demonstrate that (3)IL states of this nature are potent photodynamic agents, exhibiting the largest photocytotoxicity indices reported to date with nanomolar light cytotoxicities at very short drug-to-light intervals. Importantly, these new agents are robust enough to maintain submicromolar PDT in pigmented metastatic melanoma cells, where the presence of melanin in combination with low oxygen tension is known to compromise PDT. This activity underscores the potential of metal-organic PDT as an alternate treatment strategy for challenging environments such as malignant melanoma.

Jadomycin Oct (1) was isolated from Streptomyces venezuelae ISP5230 and characterized as a structurally unique eight-membered l-ornithine ring-containing jadomycin. The structure was elucidated through the semisynthetic derivatization of starting material via chemoselective acylation of the l-ornithine α-amino group using activated succinimidyl esters. Incorporation of 5-aminovaleric acid led to jadomycin AVA, a second eight-membered ring-containing jadomycin. These natural products illustrate the structural diversity permissible from a non-enzymatic step within a biosynthetic pathway and exemplifies the potential for discovery of novel scaffolds.

The purpose of the present investigation was to ascertain whether (3)IL excited states with microsecond lifetimes are universally potent for photodynamic applications, and if these long-lived states are superior to their (3)MLCT counterparts as in vitro PDT agents. A family of blue-green absorbing, Ru(II)-based transition metal complexes derived from the π-expansive dppn ligand was prepared and characterized according to its photodynamic activity against HL-60 cells, and toward DNA in cell-free media. Complexes in this series that are characterized by low-energy and long-lived (3)IL excited states photocleaved DNA with blue, green, red, and near-IR light. This panchromatic photodynamic effect translated to in vitro multiwavelength photodynamic therapy (PDT) with red-light cytotoxicities as low as 1.5 μM (EC50) for the parent complex and 400 nM for its more lipophilic counterpart. This potency is similar to that achieved with Ru(II)-based dyads containing long-lived (3)IL excitons located on appended pyrenyl units, and appears to be a general property of sufficiently long-lived excited states. Moreover, the red PDT observed for certain members of this family was almost 5 times more potent than Photofrin with therapeutic indices 30 times greater. Related Ru(II) complexes having lowest-lying (3)MLCT states of much shorter duration (≤1 μs) did not yield DNA photodamage or in vitro PDT with red or near-IR light, nor did the corresponding Os(II) complex with a submicrosecond (3)IL excited state lifetime. Therefore, metal complexes that utilize highly photosensitizing (3)IL excited states, with suitably long lifetimes (≫ 1 μs), are well-poised to elicit PDT at wavelengths even where their molar extinction coefficients are very low (

Human parvovirus B19 (B19) is a common pathogen which causes a variety of diseases. Persistent B19 infection is related to the degree of host immunodeficiency in patients with human immunodeficiency virus (HIV) infection. However, the existence, loading, virus evolution and distribution of B19 in Chinese HIV-positive patients have not been determined.We investigated 573 HIV-positive blood donors and AIDS patients in Sichuan, China in the last two decades. Bl9-specific serology and quantitative polymerase chain reaction were used to determine the prevalence of B19/HIV co-infection. Viral genome fragments were subjected to phylogeny and haplotype analysis.B19 genomic DNA was found in 26 of 573 (4.5%) HIV-positive individuals, a higher prevalence than in blood donors. DNA levels ranged from 5.3×10(2)-1.1×10(5) copies/mL. The seroprevalence of IgG was significantly lower in HIV-positive samples than in HIV-negative blood donors, indicating deficient production of B19-specific IgG in the former. The B19 isolates were genotype-1 subtype B19-1A which formed a monophyletic group; seven distinct haplotypes were discovered with 60% of the B19/HIV co-infected variants sharing one central haplotype.This study on the prevalence, phylogeny and distribution of human parvovirus B19 in Sichuan, China, demonstrates the persistence of B19 in the circulation of both immunocompetent and immunocompromised subjects, with implications for blood safety.

Background In China, high prevalence of HBV and HCV parallels with the growing epidemic of syphilis and HIV in the general population poses a great threat to blood safety. This study investigated the prevalence of serologic markers for transfusion transmissible infections (TTIs) among four Chinese blood centers. Methods We examined whole blood donations collected from January 2000 through December 2010 at four Chinese blood centers. Post-donation testing of TTIs (HIV, HBV, HCV and syphilis) were conducted using two different enzyme-linked immunosorbent assay kits for each seromarker. The prevalence of serologic markers for TTIs (%) was calculated and additional analysis was conducted to examine donor characteristics associated with positive TTIs serology. Results Of the 4,366,283 donations, 60% were from first-time donors and 40% were from repeated donors. The overall prevalence of HIV, HBsAg, HCV and syphilis was 0.08%, 0.86%, 0.51% and 0.47%, respectively. The prevalence profile of TTIs varied among different blood centers and appeared at relatively high levels. Overall, the prevalence of HBsAg and HCV demonstrated a decline trend among four blood centers, while the prevalence of HIV and syphilis displayed three different trends: constantly steady, continually increasing and declining among different centers. Conclusions This study reflects the risk of TTIs has been greatly reduced in China, but blood transfusion remains an ongoing risk factor for the spread of blood-borne infections, and further work and improvements are needed to strengthen both safety and availability of blood in China.