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Development of new photosensitizers (PSs) with high singlet oxygen quantum yield and minimal side effects is of great interest in photodynamic therapy (PDT). Herein, a facile strategy to significan...

Summary In conventional photodynamic therapy (PDT), reactive oxygen species are produced to kill cancer cells based on type-I and type-II mechanisms, and the sensitization of photosensitizers is oxygen dependent. However, solid tumors reside in a hypoxic milieu, which hampers the therapeutic efficacy of photosensitive drugs against tumors. Novel photosensitizers NBEX (X = S, Se, Te) were designed to bind to RNA without interference by other species and to transfer excitation-state energy directly to destroy RNA in cancer cells. This process of killing cancer cells is completely independent of oxygen (type-III mechanism). Remarkably, NBEX (X = S, Se, Te) could self-assemble into nanoparticles and accumulate in the tumor area within tens of minutes in vivo. NBESe exhibited an excellent performance for killing solid tumors and inhibited tumor metastasis. Simultaneously, PDT could induce the immune response to tumors. This novel photosensitizer could be a candidate for cancer treatment in clinical practice.

Antibiotic abuse causes the emergence of bacterial resistance. Photodynamic antibacterial chemotherapy (PACT) has great potential to solve serious bacterial resistance, but it suffers from the inefficient generation of ROS and the lack of bacterial targeting ability. Herein, a unique cationic photosensitizer (NB) and bacteriophage (ABP)-based photodynamic antimicrobial agent (APNB) is developed for precise bacterial eradication and efficient biofilm ablation. Thanks to the structural modification of the NB photosensitizer with a sulfur atom, it displays excellent reactive oxygen species (ROS)-production ability. Moreover, specific binding to pathogenic microorganisms can be provided by bacteriophages. The developed APNB has multiple functions, including bacteria targeting, near-infrared fluorescence imaging and combination therapy (PACT and phage therapy). Both in vitro and in vivo experiments prove that APNB can efficiently treat A. baumannii infection. Particularly, the recovery from A. baumannii infection after APNB treatment is faster than that with ampicillin and polymyxin B in vivo. Furthermore, the strategy of combining bacteriophages and photosensitizers is employed to eradicate bacterial biofilms for the first time, and it shows the excellent biofilm ablation effect as expected. Thus, APNB has huge potential in fighting against multidrug-resistant bacteria and biofilm ablation in practice.

Antibiotic abuse causes the emergence of bacterial resistance. Photodynamic antibacterial chemotherapy (PACT) has great potential to solve serious bacterial resistance, but it suffers from the inefficient generation of ROS and the lack of bacterial targeting ability. Herein, a unique cationic photosensitizer (NB) and bacteriophage (ABP)-based photodynamic antimicrobial agent (APNB) is developed for precise bacterial eradication and efficient biofilm ablation. Thanks to the structural modification of the NB photosensitizer with a sulfur atom, it displays excellent reactive oxygen species (ROS)-production ability. Moreover, specific binding to pathogenic microorganisms can be provided by bacteriophages. The developed APNB has multiple functions, including bacteria targeting, near-infrared fluorescence imaging and combination therapy (PACT and phage therapy). Both in vitro and in vivo experiments prove that APNB can efficiently treat A. baumannii infection. Particularly, the recovery from A. baumannii infection after APNB treatment is faster than that with ampicillin and polymyxin B in vivo. Furthermore, the strategy of combining bacteriophages and photosensitizers is employed to eradicate bacterial biofilms for the first time, and it shows the excellent biofilm ablation effect as expected. Thus, APNB has huge potential in fighting against multidrug-resistant bacteria and biofilm ablation in practice., APNB for multidrug-resistant A. Baumannii therapy and biofilms ablation.

CD13/aminopeptidase N (APN), which is a zinc-dependent metalloproteinase, plays a vital role in the growth, migration, angiogenesis, and metastasis of tumours. Thus, in situ molecular imaging of endogenous APN levels is considerably significant for investigating APN and its different functions. In this study, a novel two-photon near-infrared (NIR) fluorescence probe DCM-APN was prepared to perform in vitro and in vivo tracking of APN. The N-terminal alanyl site of probe DCM-APN was accurately hydrolysed to the amino group, thereby liberating strong fluorescence owing to the recovery of the Intramolecular Charge Transfer (ICT) effect. By considering its outstanding selectivity, ultra-sensitivity (DL 0.25 ng mL−1) and favourable biocompatibility, the probe DCM-APN was used to distinguish between normal cells (LO2 cells) and cancer cells (HepG-2 and B16/BL6 cells). Furthermore, migration of hepatocellular carcinoma cells was apparently inhibited by ensuring that the APN catalytic cavity was occupied by bestatin. The identification of three-dimensional (3D) fluorescence in cancer tissues was completed under two-photon excitation coupled with lighting up hepatocellular carcinoma tumours in situ; this revealed that probe DCM-APN is an effective tool for detecting APN, thereby assisting in the early diagnosis of tumour in clinical medicine.

Immune checkpoint blockade (ICB) therapy currently considered as to be effective way to cure cancer in clinic. However, the insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment always result in diminished efficacy of immunotherapy. Herein, we report the synthesis of an organic photo-immune activator NBS-1MT, the combination of photosensitizer and Indoleamine 2,3-dioxygenase (IDO) inhibitor effectively stimulates lysosomes oxidative stress the releases inflammatory cytokines. This process triggers pyroptosis for the considerable immunogenic cell death (ICD) while reversing suppressive tumor microenvironment. The photo-immune drug shows outstanding potential to activate caspase-1and then remove gasdermin-D (GSDMD), which could stimulate pyroptosis and also inhibit the tumor growth successfully in both primary and distant tumor. Furthermore, pyroptosis activated by photodynamic therapy (PDT) promotes the immune related factors release, and enhance the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) with the induction of ICD of tumor cells and the cascaded synergize with IDO inhibitor, so the general antitumor immune response could be strengthened effectively. Our research confirms that the use of NBS-1MT is a promising strategy to boost the immune response and eventually to inhibit tumor growth.

In recent years, the use of aggregation-induced emission luminogens (AIEgens) for biological imaging and phototherapy has become an area of intense research. However, most traditional AIEgens suffer from undesired aggregation in aqueous media with “always on” fluorescence, or their targeting effects cannot be maintained accurately in live cells with the microenvironment changes. These drawbacks seriously impede their application in the fields of bio-imaging and antitumor therapy, which require a high signal-to-noise ratio. Herein, we propose a molecular design strategy to tune the dispersity of AIEgens in both lipophilic and hydrophilic systems to obtain the novel near-infrared (NIR, ∼737 nm) amphiphilic AIE photosensitizer (named TPA-S-TPP) with two positive charges as well as a triplet lifetime of 11.43 μs. The synergistic effects of lipophilicity, electrostatic interaction, and structure-anchoring enable the wider dynamic range of AIEgen TPA-S-TPP for mitochondrial targeting with tolerance to the changes of mitochondrial membrane potential (ΔΨm). Intriguingly, TPA-S-TPP was difficult for normal cells to be taken up, indicative of low inherent toxicity for normal cells and tissues. Deeper insight into the changes of mitochondrial membrane potential and cleaved caspase 3 levels further revealed the mechanism of tumor cell apoptosis activated by AIEgen TPA-S-TPP under light irradiation. With its advantages of low dark toxicity and good biocompatibility, acting as an efficient theranostic agent, TPA-S-TPP was successfully applied to kill cancer cells and to efficiently inhibit tumor growth in mice. This study will provide a new avenue for researchers to design more ideal amphiphilic AIE photosensitizers with NIR fluorescence., In this contribution, based on a “step-by-step” molecular design strategy, a novel NIR amphiphilic AIEgen TPA-S-TPP with a triplet lifetime of 11.43 μs and surmounting the shackle of MMP was successfully fabricated for amplified tumor ablation.

China is a key region for understanding fire activity and the drivers of its variability under strict fire suppression policies. Here, we present a detailed fire occurrence dataset for China, the Wildfire Atlas of China (WFAC; 2005–2018), based on continuous monitoring from multiple satellites and calibrated against field observations. We find that wildfires across China mostly occur in the winter season from January to April and those fire occurrences generally show a decreasing trend after reaching a peak in 2007. Most wildfires (84%) occur in subtropical China, with two distinct clusters in its southwestern and southeastern parts. In southeastern China, wildfires are mainly promoted by low precipitation and high diurnal temperature ranges, the combination of which dries out plant tissue and fuel. In southwestern China, wildfires are mainly promoted by warm conditions that enhance evaporation from litter and dormant plant tissues. We further find a fire occurrence dipole between southwestern and southeastern China that is modulated by the El Niño-Southern Oscillation (ENSO)., Fire activity in China and its associations with climate are not well quantified at a local scale. Here, the authors present a detailed fire occurrence dataset for China and find a dipole fire pattern between southwestern and southeastern China that is modulated by the El Niño-Southern Oscillation (ENSO).

Heavy metal pollution is a serious concern in the urban area of China. Understanding metal pollution history is crucial for setting up appropriate measures for pollution control. Herein, we report a record of concentrations of 10 heavy metals (Fe, Mn, Cu, Zn, Ni, Cr, Cd, Pb, Co, and Sr) in Pinus massoniana tree rings from Fuzhou City over the past 168 years, which represents the longest tree-ring chronology of heavy metals in China. The studied metals displayed contrasting distribution patterns. Among them, Mn and Sr showed the strongest migration trend with peak concentrations at the pith. Co, Cd, and Pb also showed distinctively high concentrations near the boundary between heartwood and sapwood. Ni, Cu, Cr, and Fe showed an increasing trend possibly due to migration toward bark caused by physiological activities and increasing tourism activities and traffic pollution. The other elements (Cr, Fe, and Zn) with low migration revealed the historical pollution possibly discharged by the Fuzhou Shipping Bureau and other anthropogenic activities. Strong correlations between Cu content and temperature were found, which provides an alternative tree-ring proxy for climate reconstruction. This study provides a long-term perspective of the joint impacts of physiological, environmental, and climatological factors on the concentrations of heavy metals in southeastern China.

Although chemo-photodynamic therapy demonstrates promising synergetic therapeutic effects in malignant tumors, the light-controlled drug release, synergism and biocompatibility of current nanocarriers are limited. Herein, we report a red light-responsive, self-destructive carrier constructed using polyethylene glycol-modified, diselenide-bridged mesoporous silica nanoparticles. The carrier is co-encapsulated with the chemo-drug doxorubicin and the photosensitizer methylene blue for chemo-photodynamic therapy. Upon low-dose red light irradiation during photodynamic therapy (PDT), the reactive oxygen species (ROS) mediates a diselenide bond cleavage resulting in the degradation of the organosilica matrix and a dual drug release. This, in turn, results in a synergistic chemo-photodynamic performance in vitro and in vivo. More importantly, such cascade chemo-PDT boosts immunogenic cell death and robust anti-tumor immunity responses. Combination with a PD-1 checkpoint blockade further evokes a series of systemic immunity responses that suppress distant tumor growth and the pulmonary metastasis of breast cancer, as well as offer long-term protection against recurrent tumors. The presented work offers a controllable self-destruction nanoplatform for cascade-amplifying chemo-photodynamic therapy in response to external red light radiation.

Correction for ‘Activity-based NIR fluorescent probes based on the versatile hemicyanine scaffold: design strategy, biomedical applications, and outlook’ by Haidong Li et al., Chem. Soc. Rev., 2022, DOI: 10.1039/d1cs00307k.

Development of high selectivity, accurate targeted and noninvasive fluorescent probe for monitoring specific enzyme activity associated with the tumor is urgent needed for early diagnosis of cancer and clinical fluorescence interventional resection guidance treatment. Owing to the invasion of malignant tumor cells, tumor cells are mixed with normal cells in the actual tumor location, which make it quite difficult for clinician to diagnose early diagnosis of tumor as well as resection of tumor. To overcome aforementioned obstacle, herein, an ingenious enzyme-activated one and two-photon fluorescent probe TCF-GGT was constructed and synthesized including γ-GGT enzyme specific identification site and far-red fluorophore for imaging. Under simulative physiological condition, probe TCF-GGT demonstrated high selectivity, sensitivity (DL 0.014 mU/mL), rapid response (Te 14 min) for the detection of γ-GGT enzyme. By virtue of its biocompatibility, probe was employed for the identification of ovarian cancer cells (A2780 cells) from normal cells (NIH-3T3 cells), particularly in mixed cultivation dish (simulate the actual environment of tumor) through 2D&3D fluorescence imaging with “dual” mark (Nucleic acid labeling used by Hoechst 33342 dye and γ-GGT enzyme labeling used by probe TCF-GGT) for the first time. Probe TCF-GGT could be visualize endogenous γ-GGT activity in HepG-2 cells and zebrafish on the two-photon confocal platform, which is conduce to estimate the inhibitor of γ-GGT enzyme in vivo. Through NaBu (a potential anticancer drug) stimulation, the changes of γ-GGT activity were observed in living MCF-7 cells by using this probe. More importantly, the deep tissue penetration ability of far-red fluorescence allowed the two-photon fluorescent probe TCF-GGT to real-time track γ-GGT activity in tissue slices and tumor xenotransplantation model of mice by the tail vein injection, which showed that this enzyme-triggered fluorogenic probe would be a potential tool for preclinical applications of tumor resection.

Hydrogen peroxide (H2O2), one of the reactive oxygen species (ROS), plays vital roles in diverse physiological processes. Imbalance of the H2O2 is concerned with serious diseases such as cardiovascular disorders, neurodegenerative diseases, Alzheimer's disease and cancer. Therefore, it is critical to develop efficient methods for monitoring H2O2 in vivo. In this work, a two-photon excitation (860nm) NIR fluorescent turn-on probe TPNR-H2O2 for H2O2 based on Dicyanomethylene-4H-pyran fluorophore is reported, which can be used in solution detection with 13.2-fold NIR fluorescence enhancement, fast response (completed within 40min), excellent sensitivity (DL 72.48nM), and lower cellular auto-fluorescence interference. Importantly, the perfect photostability of TPNR-H2O2 clearly demonstrated that the probe could be applied to imaging intracellular H2O2 for a long time without photobleaching. In addition, through two-photon imaging, this probe was cell permeable and used to monitor the level of endogenous and exogenous H2O2 with promising biological application.

Hydrazine is highly toxic to humans and animals when inhaled or in contact with the skin. It is also a very important chemical used as propellant, metal corrosion inhibitor, pharmaceutical and intermediate. The simple detection of hydrazine in solution and biosystems becomes very important as a consequence of the foregoing applications. Herein, we report a two-photon fluorescent probing method using a NIR fluorescent chemodosimeter, displaying turn-on fluorescence and color change after cleaving an O -acetyl moiety by hydrazine, which exhibits good selectivity and sensitively in solution and living cells.

National Natural Science Foundation of China [30970481, 41471168]; China National Key Research and Development Program [2016YFA0600800]; Program for Changjiang Scholars and Innovative Research Team in University [IRT15R09]; China Scholarship Council; Rocky Mountain Tree-Ring Research, Inc.; National Science Foundation (NSF) Accelerating Innovation Research (AIR) program; NSF Hazard SEES project

Photodynamic therapy (PDT) and chemotherapy has been applied as a prospective approach in tumor therapeutics. However, suffering from the inherent hypoxia status in tumor microenvironment (TME), the anticancer efficiency is enormously restricted, especially PDT. Herein, we develop a unique liposomal encapsulated catalase (CAT), lyso-targeted NIR photosensitizer (MBDP) and doxorubicin (Dox), forming FA-L@MD@CAT, to increase tumor oxygenation by catalyzing intratumoral high-expressed H2O2 for enhancing the combination of chemo-PDT. Moreover, the enhanced tumoral oxygenation not only facilitates singlet oxygen (1O2) production but also reverses immunosuppressive TME by modulating immune cytokines to favor antitumor immunities, which significantly induce tumor death. Notably, this system also realizes specific tumor recognition to folate receptor upregulated tumors and improves intratumoral accumulation. This work provides an effective strategy to promote tumor therapeutic index, which may possess a promising future in clinical application.

To promote practical applications of photodynamic therapy, near-infrared (NIR) photosensitizers are manufactured based on fluorescence resonance energy transfer (FRET) between donors of anti-stoke NIR upconversion nanoparticles and acceptors of photodynamic chlorin e6. The manufactured FRET constructs displayed deep tissue penetration and FRET activation under 980 nm irradiation. Furthermore, surface decoration with mitochondria-targeting (4-marboxybutyl) triphenyl phosphonium bromide (TPP) led to mitochondrion-targeted accumulation of singlet oxygen resulting in potent cell apoptosis. Notably, in vivo anti-tumor test validates the complete ablation of intractable solid tumors based on single-dose treatment of our proposed photodynamic constructs. Therefore, the obtained results herald the tempting perspective of our carefully engineered photodynamic constructs, which could have broad utilities in clinical treatment of intractable premalignancies.

Photodynamic therapy is considered as a promising treatment for cancer, but still faces several challenges., Photodynamic therapy is considered as a promising treatment for cancer, but still faces several challenges. The hypoxic environment in solid tumors, imprecise tumor recognition and the lack of selectivity between normal and cancer cells extremely hinder the applications of photodynamic therapy in clinics. Moreover, the “always on” property of photosensitizers also increases the toxicity to normal tissues when exposed to light irradiation. In this study, a hypoxia-activated NIR photosensitizer ICy-N was synthesized and successfully applied for in vivo cancer treatment. ICy-N is in the inactivated state with low fluorescence whereas its NIR emission (λem = 716 nm) was induced via reduction caused by nitroreductase at the tumor site. In addition, the reduced product ICy-OH was specially located in the mitochondria and demonstrated a high singlet oxygen production under 660 nm light irradiation, which efficiently induced cell apoptosis (IC50 = 0.63 μM). The in vivo studies carried out in Balb/c mice indicated that ICy-N was suitable for precise tumor hypoxia imaging and can work as an efficient photosensitizer for restraining tumor growth through the PDT process.

Insect outbreaks are key disturbances triggering decline episodes in humid subtropical evergreen forests in eastern China. However, their long-term variability and linkages to climate are still unclear largely due to the shortness of records reporting forest damage. A retrospective approach would improve our understanding of long-term outbreak variability and its dependence on climate and relevant atmospheric circulation patterns such as the El Nino-Southern Oscillation (ENSO). This study provides a dendrochronological reconstruction of Dendrolimus punctatus outbreaks affecting Pinus massoniana in humid subtropical eastern China. We used tree-ring width and carbon isotope data from sites where outbreaks were or not were reported for the past fifty years, here considered as host and non-host sites, respectively. The results showed that inter-annual changes in carbon isotope discrimination are more sensitive to outbreaks than changes in tree-ring width. Based on carbon isotopes, we inferred that photosynthetic rates increased as a compensatory mechanism in response to insect defoliation. We reconstructed eleven insect outbreaks since 1915, which corresponded to ENSO positive phases and below-average sea surface temperatures in the central and eastern tropical Pacific Ocean. These conditions correspond to “La Nina” episodes which induce hot and dry climate conditions across the study region and these may facilitate the occurrence of D. punctatus outbreaks.

Photodynamic therapy has been developed as a prospective cancer treatment in recent years. Nevertheless, conventional photosensitizers suffer from lacking recognition and specificity to tumors, which causing severe side effects to normal tissues, while the enzyme-activated photosensitizers are capable of solving these conundrums due to high selectivity towards tumors. APN (Aminopeptidase N, APN/CD13), a tumor marker, has become a crucial targeting substance owing to its highly expressed on the cell membrane surface in various tumors, which has become a key point in the research of anti-tumor drug and fluorescence probe. Based on it, herein an APN-activated near-infrared (NIR) photosensitizer (APN-CyI) for tumor imaging and photodynamic therapy has been firstly developed and successfully applied in vitro and in vivo. Studies showed that APN-CyI could be activated by APN in tumor cells, hydrolyzed to fluorescent CyI-OH, which specifically located in mitochondria in cancer cells and exhibited a high singlet oxygen yield under NIR irradiation, and efficiently induced cancer cell apoptosis. Dramatically, the in vivo assays on Balb/c mice showed that APN-CyI could achieve NIR fluorescence imaging (λem = 717 nm) for endogenous APN in tumors and possessed an efficient tumor suppression effect under NIR irradiation.

For the precision resection, development of near-infrared (NIR) fluorescent probe based on specificity identification tumor-associated enzyme for lighting-up the tumor area, is urgent in the field of diagnosis and treatment. Overexpression of γ-glutamyltranspeptidase, one of the cell-membrane enzymes, known as a biomarker is concerned with the growth and progression of ovarian, liver, colon and breast cancer compared to normal tissue. In this work, a remarkable enzyme-activated NIR fluorescent probe NIR-SN-GGT was proposed and synthesized including two moieties: a NIR dicyanoisophorone core as signal reporter unit; γ-glutamyl group as the specificity identification site. In the presence of γ-GGT, probe NIR-SN-GGT was transformed into NIR-SN-NH2, the recovery of Intramolecular Charge Transfer (ICT), liberating the NIR fluorescence signal, which was firstly employed to distinguish tumor tissue and normal tissues via simple “spraying” manner, greatly promoting the possibility of precise excision. Furthermore, combined with magnetic resonance imaging by T2 weight mode, tumor transplanted BABL/c mice could be also lit up for first time by NIR fluorescence probe having a large stokes, which demonstrated that probe NIR-SN-GGT would be a useful tool for assisting surgeon to diagnose and remove tumor in clinical practice.

We present a 260-year annual PDSI reconstruction based on a regional tree-ring width chronology of Scots pine (Pinus sylvestris var. mongolica) from four sample sites in the Daxing’an Mountains, northeast China. The model explained 38.2 % of the variance of annual PDSI during the calibration period from 1911 to 2010. Compared with local historical documents, nearby forest fire history data and hydroclimate reconstructions, our reconstruction is accurate and representative, and recorded the same dry years/periods. The drought of 1920s–1930s was more severe in the Daxing’an Mountains than in surrounding areas. A moisture increase caused by a recent rapid warming (warm-wet pattern) was identified for the Daxing’an Mountains, while a warm-dry pattern was found for the East Mongolian Plateaus (mild drier) and their transition zones: the east Mongolian Plateaus (severe drier). Overall, the dry/wet variability of the Daxing’an Mountains and its relationship with the surrounding areas might be driven by Pacific and Atlantic Ocean oscillations (e.g., ENSO, PDO, AMO, NAO and SNAO) that influence the Asian monsoon, and in turn the local temperature and precipitation that influences regional drought. However, the Monsoon Asia Drought Atlas of "Cook" might inaccurately portray dry/wet variations in the Daxing’an Mountains.

Although excellent florescent probes have been developed for DNA, good probes for RNA remain lacking. The shortage of reported and commercial RNA probes is attributable to their severe interference from DNA. As DNA and RNA have similar structures but different functions, it has been an imperative challenge to develop RNA probes that differentiate from DNA. In this study, an NIR fluorescent probe, NBE, is described, which contains a bulky julolidine group that can fit in a spacious RNA pocket and emit intense fluorescence. However, NBE has no response to DNA, as it cannot intercalate into the double strands or even in the DNA minor groove. The sensing mechanism is similar to the effect of a door-bolt. NBE shows excellent performance in RNA sensing (outstanding photostability, high selectivity and fast response), whether in aqueous buffers, fixed cells or living cells. These findings might provide not only a potential imaging tool but also a new design strategy for the recognition of RNA while avoiding interference from DNA.

Comparison of the staminate flower and pollen of Betula platyphylla between autotetraploid and diploid individuals may reveal the reason for cross sterility when an autotetraploid male parent is crossed with a diploid female parent. Staminate flowers and pollen from seven autotetraploid individual trees were examined. The morphologies of the staminate flower and pollen and pollen germination of these autotetraploid individuals were compared with diploid trees. The structure of the staminate flower did not differ between autotetraploids and diploids, whereas the size of the staminate flower was larger in the autotetraploids compared with the diploids. The mean diameter and pore depth of the pollen were signifi- cantly larger in autotetraploid individuals compared with diploids, and several abnormalities in pollen mor- phology were found commonly amongst pollen from the autotetraploid trees. The germination rate of pollen from autotetraploids was significantly inferior to that of diploids and there was a significant negative correla- tion between germination rate and the percentage of abnormal pollen. These results demonstrate that the autotetraploid should not be chosen as the male parent to obtain hybrid triploid progenies because the pollen is abnormal and results in low fertility despite its large size. The results provide important information for se- lecting and distributing parent strains with the aim of building seed orchards of triploid birch trees.