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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...

Color photoresists are the key materials for the fabrication of color filters (CFs). Organic dyes offer a promising alternative to the conventional pigment-based system to make CFs with higher resolution. However, the stability of dye molecules is an urgent problem to be solved. Herein, we designed and synthesized a series of highly stable zinc phthalocyanine dyes containing polymerizable acrylamide groups. Upon light exposure, dense and insoluble network structures were formed in the prepared color filters, which increase the thermal stability and anti-migration capacity of these dyes.

The frequent occurrence of fatalities from wildfires is an ongoing problem in China, even though great improvements have been achieved in overall wildfire management in recent years. We analysed the occurrence patterns and correlative environments of fatalities from forest fires in China from 1951 to 2018. Changes in fire policies affected changes in the numbers of fires, forest area burned and number of fatalities before and after 1987, after the large Great Black Dragon Fire that burned in the Daxing’anling Mountains in northeastern China. Most fatalities occurred in the southern, southwestern and eastern forest regions of the country where population centres are concentrated, while most of the burned area was distributed in forests of northeast China with fewer population centres. Fatalities were correlated with higher values of fire weather indices, coniferous forests, coniferous and broad-leaved mixed forests, moderate–average slopes (5.1–15°), and primarily small fires of less than 100 ha in area. These results should be a first step to help improve awareness of inherent dangers during wildfires and to assist fire managers and policy-makers in strengthening safety procedures for both professional firefighters and the public to reduce wildfire fatalities in the future.

The discovery of a near-infrared (NIR, 650-900 nm) fluorescent chromophore hemicyanine dye with high structural tailorability is of great significance in the field of detection, bioimaging, and medical therapeutic applications. It exhibits many outstanding advantages including absorption and emission in the NIR region, tunable spectral properties, high photostability as well as a large Stokes shift. These properties are superior to those of conventional fluorogens, such as coumarin, fluorescein, naphthalimides, rhodamine, and cyanine. Researchers have made remarkable progress in developing activity-based multifunctional fluorescent probes based on hemicyanine skeletons for monitoring vital biomolecules in living systems through the output of fluorescence/photoacoustic signals, and integration of diagnosis and treatment of diseases using chemotherapy or photothermal/photodynamic therapy or combination therapy. These achievements prompted researchers to develop more smart fluorescent probes using a hemicyanine fluorogen as a template. In this review, we begin by describing the brief history of the discovery of hemicyanine dyes, synthetic approaches, and design strategies for activity-based functional fluorescent probes. Then, many selected hemicyanine-based probes that can detect ions, small biomolecules, overexpressed enzymes and diagnostic reagents for diseases are systematically highlighted. Finally, potential drawbacks and the outlook for future investigation and clinical medicine transformation of hemicyanine-based activatable functional probes are also discussed.

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.

Efficiency of standard chemotherapy is dramatically hindered by intrinsic multidrug resistance (MDR). Recently, to amplify therapeutic efficacy, photodynamic therapy (PDT)-induced mitochondrial dysfunction by decorating targeting moieties on nanocarriers has obtained considerable attention. Nevertheless, low targeting efficiency, complex synthesis routes, and difficulty in releasing contents become the major obstacles in further clinical application. Herein, an ingenious liposomal-based nanomedicine (L@BP) was fabricated by encapsulating a mitochondria-anchored photosensitizer (Cy-Br) and paclitaxel (PTX) for realizing enhanced cooperation therapy. At the cellular level, L@BP could hurdle endosomal traps to localize and implement PDT in mitochondria. Intriguingly, the PDT-induced in situ mitochondrial dysfunction led to intracellular ATP reduction, which triggered the downregulated P-glycoprotein transportation capacity and thus resulted in diminishing the efflux of chemotherapeutic agents and increasing drug uptake by drug-resistant cells. The prepared nanomedicine eminently accumulated in the tumor site and acquired enhanced therapeutic efficiency on PTX-resistant lung cancer cells, which possessed great potential in circumventing MDR tumors.

Chemotherapy is one of the commonly used methods to treat various types of cancers in clinic by virtue of its high efficiency and universality. However, strong side effects and low concentration of conventional drugs at the tumor site have always been important factors that plague the chemotherapy effects of patients, further precluding their practical applications. Thereof, to solve the above dilemma, by integration of anticancer drug (nitrogen mustard, NM) into an NIR fluorophore (a dicyanoisophorone derivative), an intelligent prodrug NIR-NM was developed via molecular engineering strategy. Prodrug NIR-NM stimulated in hypoxia condition exhibits significantly higher toxicity to cancer cells than normal cells, essentially reducing the collateral damage to healthy cells and tissues of nitrogen mustard. More importantly, the nanoparticle prodrug FA-lip@NIR-NM showed the advantages of the high accumulation of drug at tumor site and long-circulation capacity in vivo , which endowed it the ability to track the release of the active chemotherapeutic drug and further treat solid tumors.

Singlet oxygen (1O2) is a strong oxidant which plays important roles in photodynamic therapy (PDT). The exploitation of photosensitizers with high 1O2 production is crucial to improve PDT efficiency. In this study, a radical labeled quartet photosensitizer Cy-DENT is reported with high singlet oxygen quantum yield (ΦΔ=32.3%) due to a radical enhanced inter-system crossing (ISC) process. After the introduction of 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) radical, quartet state 4[R,T] of Cy-DENT could be formed to give an over 20-fold enhancement of singlet oxygen quantum yield compared to Cy-DEN (without TEMPO radical) under irradiation of near infrared (NIR) light. In addition, the 1O2 production is well controlled by varying the electron-donating ability of the terminal substituent group. Cy-DENT possesses good cell permeability and is localized in mitochondria. Under the irradiation of 700 nm light, Cy-DENT can produce high levels of ROS to destroy the mitochondria membrane potential and induce cell apoptosis. Through the encapsulation of PEG-SS-PCL micelle, Cy-DENT can be effectively delivered to tumors and suppresses the tumor growth after PDT treatment.

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.

Accurate sensing of endogenous microRNAs remains a great challenge for unsatisfactory signal-to-background ratios of traditional techniques. Meanwhile, low sensitivity and insufficient specificity ...

Palladium(0) as one of the vital transition metals, is employed in numerous industries, such as drug synthesis, aerospace high-tech field and automobile industry. When the Pd(0) enter into the body, it will bind with thiol-containing amino acids, DNA, RNA, and other biomolecules damaging to human health. Thus, developing a novel tool for monitoring and imaging of Pd(0) in vivo is very urgent. In the work, based on a intramolecular charge transfer (ICT) mechanism a two-photon fluorescent probe NIPd had been designed and synthesized for the recognition Pd(0). In vitro experiments data displayed that probe NIPd exhibited a 13-fold fluorescent increase for Pd(0) in 30 min in the aqueous solution with a detection limit of 16 nmol/L. It also showed the outstanding selectivity and antijamming performance. More importantly, NIPd could be served as a two-photon fluorescent probe for real-time monitoring Pd(0) in living cells and mice.

Photodynamic therapy (PDT) has drawn significant attention as a noninvasive cancer treatment. At present, PDT applications are limited in vivo because of the short lifetime and limited diffusion distance of cytotoxic reactive oxygen species (ROS) in the cellular environment. We propose to overcome this challenge by generating limited and short-lived ROS that are localized in key organelles, particularly the nucleus, in tumor cells. We developed Se/N-doped carbon dots (Se/N-CDs) as a photosensitizer for PDT. The Se/N-CDs were shown to bind RNA selectively by digestion experiments, isothermal titration microcalorimetry, and cell dyeing with RNA probes. Se/N-CDs near the nuclear membrane produced ROS that damaged the membrane under light irradiation, permitting the entry of more Se/N-CDs and thereby improving the conversion efficiency of photosensitization. Furthermore, in vitro and in vivo experiments indicated that the Se/N-CDs could inhibit tumor growth more effectively by PDT within the nucleus.

The recurrence of malignant tumors is mostly caused by incompleted surgical resection. Especially, it is difficult for surgeons to detect and accurately remove metastatic tumors by predominantly using visual examination and palpation owing to the lack of effective means to specifically distinguish the boundary range between normal and tumor tissues. Thus, the development of activated fluorescent probe with superior tumor-to-normal (T/N) tissue ratios is particularly urgent in clinics. In view of CD13/aminopeptidase N (APN) regarded as a cancer-specific biomarker, mediating with progression, invasion, and migration of malignant tumor, herein, we reported an APN-responsive fluorescent probe YH-APN and demonstrated its application to distinguish cancer cells. Through in situ spraying manner, fluorescent superior tumor-to-normal (T/N) tissue ratios (subcutaneous transplantation tumor, 13.86; hepatic metastasis, 4.42 and 6.25; splenic metastasis, 4.99) were achieved. More importantly, we have demonstrated the ability to image metastasis tumor tissue less than 1 mm in diameter, highlighting the potential for this probe to be used as a tool in surgical resection. This research may spur the use of enzyme-activatable fluorescent probes for the progress of tumor diagnosis and image-guided surgery (IGS).

Monitoring fluctuations in enzyme overexpression facilitates early tumor detection and excision. An AIEgen probe (DQM-ALP) for the imaging of alkaline phosphatase (ALP) activity was synthesized. The probe consists of a quinoline-malononitrile (QM) core decorated with hydrophilic phosphate groups as ALP-recognition units. The rapid liberation of DQM-OH aggregates in the presence of ALP resulted in aggregation-induced fluorescence. The up-regulation of ALP expression in tumor cells was imaged using DQM-ALP. The probe permeated into 3D cervical and liver tumor spheroids for imaging spatially heterogeneous ALP activity with high spatial resolution on a two-photon microscopy platform, providing the fluorescence-guided recognition of sub-millimeter tumorigenesis. DQM-ALP enabled differentiation between tumor and normal tissue ex vivo and in vivo, suggesting that the probe may serve as a powerful tool to assist surgeons during tumor resection.

The principle of photochemical transformation has shown significant inspiration on phototherapy of solid tumors. However, both photodynamic therapy (PDT) and photothermal therapy (PTT) can induce stress response of tumor cells, which draw the attention in recent. Herein, an asymmetric and lollipop like nanostructure consisting of gold nanorod/titanium dioxide (l-TiO

Heavy-atom-based photosensitizers usually exhibit shortened triplet-state lifetimes, which is not ideal for hypoxic tumor photodynamic therapy. Although several heavy-atom-free photosensitizers possess long triplet-state lifetimes, the clinical applicability is limited by their short excitation wavelengths, poor photon capture abilities, and intrinsically hydrophobic structures. Herein we developed a novel NIR heavy-atom-free photosensitizer design strategy by introducing sterically bulky and electron-rich moieties at the meso position of the pentamethine cyanine (Cy5) skeleton, which simultaneously enhanced intersystem crossing (ISC) and prolonged excited-state lifetime. We found that the 1O2 generation ability is directly correlated to the electron-donating ability of the meso substituent in cyanine, and the excited-state lifetime was simultaneously much elongated when the substituents were anthracene derivatives substituted at the 9-position. Our star compound, ANOMe-Cy5, exhibits intense NIR absorption, the highest 1O2 quantum yield (4.48-fold higher than Cy5), the longest triplet-state lifetime (9.80-fold longer than Cy5), and lossless emission intensity (nearly no change compared with Cy5). Such excellent photophysical properties coupled with its inherently cationic and hydrophilic nature enable the photosensitizer to realize photoablation of solid tumor and antitumor lung metastasis. This study highlights the design of a new generation of NIR photosensitizers for imaging-guided photodynamic cancer treatment.

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.

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.

Plant community resilience in frequent-fire forests of western North America has been compromised by over a century of fire exclusion. However, there are several western National Parks where fires have been reintroduced over the past several decades, including Zion National Park in southwest Utah. Here we reconstruct historical components of fire regimes in ponderosa pine dominated forests at Zion and compare these to recent fire frequency, current plant community and fuels structure, and potential fire behavior. Historical fires burned every 9–10 years on average up until 1879, when fires ceased contemporaneous with introduction of Euro-American livestock grazing and timber harvest in upland forests. Abundant tree regeneration occurred after fire exclusion, with tree density averaging 45 trees ha−1 in reconstructed 1880 forests versus 106 trees ha−1 today. Intervals between recent (since 1988) wildfires and prescribed fires in these same stands ranged from 7 to 13 years, similar to historical fire timing. Depending on whether plots had burned from zero to three times in recent fires, we found significant differences in canopy base heights (increased), duff and litter depths (decreased), and percent cover of grass and forbs (increased), but not tree density, tree basal area, shrub height, shrub cover, or woody fuels. Combined effects of recent fires on overstory and understory structure resulted in a significant difference in likelihood of crown fire occurrence, declining from a mean of 58% in plots with no fire since 1879 to 13% in plots with three fires since 1988. Significant effects were generally seen after two or three fires, suggesting it is the reintroduction of the fire regime and not just individual fire events that restore resiliency. Overall, effects of recent fires are building on the latent resiliency of ponderosa pine forests at Zion National Park, although questions remain about extent and future dynamics of oak and manzanita shrubfields that occupy similar environmental settings, along with a general lack of ponderosa pine regeneration across all plots.

A microenvironment-sensitive probe SCD is developed with a thiol-activated functional group, which could identify specific proteins containing free cysteine residues, such as human serum albumin (HSA), bovine serum albumin (BSA), and β-lactoglobulin. The probe displays good selectivity and sensitivity toward thiol-containing proteins over other proteins, ions, and amino acids under physiological conditions. Due to the twisted intramolecular charge transfer property, SCD exhibits a fluorescence “turn-on” which is utilized for the quantitative detection of trace HSA contents in urine and serum media for the assessment of kidney function and diagnosis of renal diseases. Furthermore, SCD realizes HSA imaging in human breast cancer cells.

The overexpression of nitroreductase (NTR) in hypoxia has been recognized as a biomarker of highly aggressive disease, and the development of a hypoxia-sensitive two-photon (TP) bioimaging probe with both excitation and emission wavelengths in the red-light region provides favorable deep-tissue imaging with a low background fluorescence signal. Although quite a few TP hypoxia-sensitive fluorescent probes have been reported for NTR detection, their short emission wavelength (

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.

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.

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.

Surgical assailment at the vulnerable subcellular organelles (e.g. mitochondria) by photodynamic therapy (PDT) is perceived as the most devastating approach to eradicate the tumors. Herein, we programmed a novel near-infrared (NIR) PDT construct illustrating appreciable hierarchical zoom-in targeting scenario, namely, primary cell-level targeting to carcinoma post systemic dosage and subcellular level targeting to mitochondria. Pertaining to tumor-targeting function, charge reversal chemistry selectively responsive to acidic tumoral microenvironments (pH 6.8) was implemented as the external corona of PDT constructs. This charge transformative exterior entitled minimal biointerfacial reactions in systemic retention but intimate affinities to cytomembranes selectively in tumoral microenvironments, thereby resulting in preferential uptake by tumors. Furthermore, the proposed PDT constructs were equipped with mitochondria targeting triphenylphosphonium (TPP) motif, which appeared to propel intriguing 88% colocalization with mitochondria. Therefore, overwhelming cytotoxic potencies were accomplished by our carefully engineered photodynamic constructs. Another noteworthy is the photodynamic constructs characterized to be excited at tissue-penetrating NIR (980 nm) based on energy transfer between their internal components of anti-Stoke upconversion nanoparticles (UCN, donor) and photodynamic chlorin e6 (Ce6, acceptor). Therefore, practical applications for photodynamic treatment of intractable solid carcinoma were greatly facilitated and complete tumor eradication was achieved by systemic administration of the ultimate multifunctional NIR photodynamic constructs.