Rising CO2 and land use change amplify the increase in terrestrial and riverine export of dissolved organic carbon over the past four decades.

The lateral transport of dissolved organic carbon (DOC) from land to rivers and oceans is a significant but overlooked component of the global carbon cycle. However, there are still large uncertainties in the magnitude and trend of global DOC export fluxes, as well as their response to environmental change. In this study, several simulations were conducted using a developed land surface model that considered riverine DOC transport and anthropogenic disturbance to investigate the terrestrial DOC loading and riverine DOC export, and to quantify the relative contributions of natural and anthropogenic factors over the past four decades (1981-2016). These factors include climate change, nitrogen deposition, land use change, atmospheric CO2 concentration, anthropogenic water regulation, and fertilizer and manure application. Results showed that the average global annual terrestrial DOC loading was about 432.30 ± 53.59 Tg C yr-1, and rivers exported about 209.73 ± 36.58 Tg C yr-1 to oceans over the past four decades. Simultaneously, a significant increase in terrestrial DOC loading and riverine DOC export fluxes (3.36 Tg C yr-2 and 2.99 Tg Cyr-2, p < 0.01) was found, which increased by 26.88 % and 47.02 %, respectively. According to our factorial analysis, the interannual variability in DOC fluxes in most regions was mainly attributed to climate change and contributed more than 60 % of the long-term increase. In addition, rising atmospheric CO2 and land use change amplified the increase in terrestrial DOC loading, with the area dominated by the two factors expanding from 7.94 % in the 1980s to 23.84 % in the 2010s, and riverine DOC export showed a similar pattern, which may be related to the increased soil DOC sources. Anthropogenic water regulation and nitrogen addition have led to a slight increase in DOC fluxes, which should not be ignored, otherwise carbon fluxes may be underestimated.

The reward and penalty for ozone pollution control caused by natural sources and regional transport: A case study in Guangdong province.

Ground-level O3 pollution in the Pearl River Delta region (PRD) is closely related to anthropogenic, natural emissions and regional transport. However, the interactions among different sources and natural intervention in modulating anthropogenic management have not been comprehensively assessed. Here, the WRF-CMAQ-MEGAN modeling system was utilized to simulate an O3 episode over PRD. The integrated source apportionment method (ISAM) and brute-force top-down combined with factor separation approach (BF-TD-FSA) were applied to quantify source contributions, impacts of individual or multiple sources on O3, and decouple interactions among various emissions; additionally, based on ISAM, O3 isopleths visualized MDA8 O3 response of different source types to anthropogenic perturbations. ISAM concluded considerable MDA8 O3 contributions of regional transport in PRD/NPRD (non-PRD areas in Guangdong province) (38.8 %/35.7 %), followed by anthropogenic (32.7 %/24.8 %), BVOC (biogenic volatile organic compounds, 23.8 %/20.3 %) and SNO (soil NO, ∼4 %) emissions. Compared to concentrated anthropogenic contributions, widespread natural contributions were observed across their source areas and along the transport pathways. The BF-TD also revealed that regional transport had the largest impact (>90 µg m-3) on MDA8 O3 while anthropogenic and BVOC emissions greatly affected downwind PRD (64.5 and 7.7 µg m-3). Negative synergy between anthropogenic and natural emissions (especially BVOC emission) suggested potential natural-induced intensification of anthropogenic impact during O3 management. The MDA8 O3 isopleths further demonstrated significant BVOC-induced reward and regional transport-induced penalty for anthropogenic NOx (ANOx) emission control benefits, leading to additional maximum MDA8 O3 decrease and increase by -27.5 and 13.8 µg m-3 in polluted high-emission grids. The natural-induced reward effect could impose loose requirements on anthropogenic reduction (decreased by 13.3 %-17.7 %) if there were no regional transport-induced control penalty. It is advisable to prioritize ANOx control and seek collaboration on air quality management with neighboring provinces to maximize the natural-induced control reward and achieve desired targets with minimal human efforts.

Recent advances of small molecule detection in nanopore sensing.

Due to its advantages of label-free and highly sensitive, the resistive pulse sensing with a nanopore has recently become even more potent for the discrimination of analytes in single molecule level. Generally, a transient interruption of ion current originated from the captured molecule passing through a nanopore will provide the rich information on the structure, charge and translocation dynamics of the analytes. Therefore, nanopore sensors have been widely used in the fields of DNA sequencing, protein recognition, and the portable detection of varied macromolecules and particles. However, the conventional nanopore devices are still lack of sufficient selectivity and sensitivity to distinguish more metabolic molecules involving ATP, glucose, amino acids and small molecular drugs because it is hard to receive a large number of identifiable signals with the fabricated pores comparable in size to small molecules for nanopore sensing. For all this, a series of innovative strategies developed in the past decades have been summarized in this review, including host-guest recognition, engineering alteration of protein channel, the introduction of nucleic acid aptamers and various delivery carriers integrating signal amplification sections based on the biological and solid nanopore platforms, to achieve the high resolution for the small molecules sensing in micro-nano environment. These works have greatly enhanced the powerful sensing capabilities and extended the potential application of nanopore sensors.

Acoustic hologram-induced virtual in vivo enhanced waveguide (AH-VIEW).

Optical imaging and phototherapy in deep tissues face notable challenges due to light scattering. We use encoded acoustic holograms to generate three-dimensional acoustic fields within the target medium, enabling instantaneous and robust modulation of the volumetric refractive index, thereby noninvasively controlling the trajectory of light. Through this approach, we achieved a remarkable 24.3% increase in tissue heating rate in vitro photothermal effect tests on porcine skin. In vivo photoacoustic imaging of mouse brain vasculature exhibits an improved signal-to-noise ratio through the intact scalp and skull. These findings demonstrate that our strategy can effectively suppress light scattering in complex biological tissues by inducing low-angle scattering, achieving an effective depth reaching the millimeter scale. The versatility of this strategy extends its potential applications to neuroscience, lithography, and additive manufacturing.

Comparative analysis for the impacts of VOC subgroups and atmospheric oxidation capacity on O3 based on different observation-based methods at a suburban site in the North China Plain.

The persistent O3 pollution in the Beijing-Tianjin-Hebei (BTH) region remains unresolved, largely due to limited comprehension of O3-precursor relationship and photochemistry drivers. In this work, intraday O3 sensitivity evolution from VOC-limited (volatile organic compound) regime in the forenoon to transition regime in the late afternoon was inferred by relative incremental reactivity (RIR) in summer 2019 at Xianghe, a suburban site in BTH region, suggesting that VOC-focused control policy could combine with stringent afternoon NOx control. Then detailed impacts of VOC subgroups on O3 formation were further comprehensively quantified by parametric OH reactivity (KOH), O3 formation potential (OFP), as well as RIR weighted value and O3 formation path tracing (OFPT) approach based on photochemical box model. O3 episode days corresponded to stronger O3 formation, depicted by higher KOH (10.4 s-1), OFP (331.7 µg m-3), RIR weighted value (1.2), and F(O3)-OFPT (15.5 ppbv h-1). High proportions of isoprene and OVOCs (oxygenated VOCs) to the total KOH and the OFPT method were demonstrated whereas results of OFP and RIR-weighted presented extra great impacts of aromatics on O3 formation. The OFPT approach captured the process that has already happened and included final O3 response to the original VOC, thus reliable for replicating VOC impacts. The comparison results of the four methods showed similarities when utilizing KOH and OFPT methods, which reveals that the potential applicability of simple KOH for contingency VOC control and more complex OFPT method for detailed VOC- and source-oriented control during policy-making. To investigate propulsion of VOC-involved O3 photochemistry, atmospheric oxidation capacity (AOC) was quantified by two atmospheric oxidation indexes (AOI). Both AOIp_G (7.0 × 107 molec cm-3 s-1, potential AOC calculated by oxidation reaction rates) and AOIe_G (8.5 µmol m-3, estimated AOC given redox electron transfer for oxidation products) were stronger on O3 episode days, indicating that AOC promoted the radical cycling initiated from VOC oxidation and subsequent O3 production. Result-oriented AOIe_G reasonably characterized actual AOC inferred by good linear correlation between AOIe_G and O3 concentrations compared to process-oriented AOIp_G. Therefore, with continuous NOx abatement, AOIe_G should be considered to represent actual AOC, also O3-inducing ability.

Design of a simple and low-cost solid-state ultra-fast high-voltage switch.

Ultra-fast high-voltage switches (UFHVSs) are a core component of time-of-flight mass spectrometers for realizing high accuracy ion acceleration, deceleration, and temporal focusing. The desirable features of high performance UFHVSs include a large range of adjustability of pulse width, a high maximum output amplitude, and minute rising and falling times. Besides the simplicity of the driver circuit, the total cost of the whole device is also critical to its practical applications. In this work, we present a low-cost and easy-fabrication 5000 V bipolar solid-state UFHVS for a high-resolution mass spectrometer. A double-pulse transformer isolates the circuit's high- and low-voltage sides and synchronously drives series-connected cascode SiC FETs to form its push-pull topology. This scheme allows transmitting drive signals with long widths but without the magnetic saturation of the transformer. Testing results show that output pulses reach a maximum voltage of 5000 V and a width of 150 µs, with rising and falling times of 8.5 and 18.3 ns, respectively. More importantly, they have nearly no voltage decay.

Maximizing ozone control by spatial sensitivity-oriented mitigation strategy in the Pearl River Delta Region, China.

The Pearl River Delta (PRD) has long been plagued by severe O3 pollution, particularly during the autumn. A regional O3 pollution episode influenced by the Western Pacific Subtropical High in September 2021 was characterized by near-surface O3 escalation due to strong photochemical reactions within the planetary boundary layer. This event was targeted to develop effective control strategies through investigation of precursor control type and scope based on the high-order decoupled direct method (HDDM) and integrated source apportionment method (ISAM) of CMAQ. Generally, the majority of areas (67.0 %) were under NOx-limited regime, which should strengthen afternoon NOx control inferred by positive convex O3 responses. However, high emission and heavily polluted areas located in central PRD were under VOC-limited regime (11.6 %) or mixed regime (15.0 %). The remaining areas (6.4 %) were under NOx-titration or insensitive conditions. Regarding source apportionment, Guangdong province contributed 32.3 %-58.4 % to MDA8 O3 of PRD, especially higher proportion (>50 %) to central areas. Overall, local-focused NOx/VOC emission reductions had limited effects on O3 mitigation for receptor cities compared to regional-cooperative regulation. When region-wide VOC emission reduction was implemented, MDA8 O3 in VOC-limited grids exhibited the largest declines (2.3 %-4.1 %, 3.9- 7.0 µg·m-3). However, unified NOx control contributed to increasing MDA8 O3 in VOC-limited grids (most stations located for air quality evaluation) whereas decreased MDA8 O3 by 2.1 %- 5.7 %, 3.0- 8.2 µg·m-3 in large-scale NOx-limited grids. The sensitivity-oriented regional control avoided O3 rebound and achieved the greatest decline of 3.4 %- 5.0 %, 5.7- 8.4 µg·m-3 in VOC-limited grids; additionally, time-refined dynamic aggressive NOx control decreased peak O3 by an extra 1.2- 6 µg·m-3, both of which facilitate the regulation for the forecasting O3 episodes. These findings suggest that in heavily polluted environments, the enhancement of O3 regulation benefits requires meticulous, coordinated, and dynamic NOx and VOC controls spanning the entire region based on high-resolution analysis of heterogeneous O3-NOx-VOC sensitivity. Furthermore, emission reduction gains should be more reasonably reflected through increasing in-situ observations covering multi-sensitivity regions.

Quercetin reverses 5-fluorouracil resistance in colon cancer cells by modulating the NRF2/HO-1 pathway.

Quercetin (Que) has been proven to enhance the chemosensitivity of multiple cancers, including colon cancer (CC). However, whether the combination of Que and 5-fluorouracil (5-FU) has a synergistic effect on drug-resistant CC cells has not previously been reported. The effect of Que (5 and 10 µg/mL) on cell vitality and apoptosis of CC and CC drug-resistant cells was examined using a cell counting kit-8 (CCK-8) and flow cytometry. After cells were treated with 5-FU (10, 40 µg/mL), Que (10 µM, 40 µM), or 5-FU in combination with Que, cell proliferation, apoptosis, oxidative stress-related factors, reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway-related factors were examined by colony formation assay, flow cytometry, ELISA, ROS kit, immunofluorescence assay, and Western blot. The results showed that 5-FU reduced cell viability and induced apoptosis of CC as well as 5-FU-resistant CC cells. Que further restrained the proliferation, oxidative stress-related factors (SOD, CAT, GPx, and GR), ROS production, and induced apoptosis in CC cells and 5-FU-resistant CC cells induced by 5-FU. Moreover, the combination of Que and 5-FU attenuated the Nrf2/HO-1 pathway-related marker levels in CC cells and 5-FU-resistant CC cells. Therefore, our results suggest that Que reverses 5-FU resistance in CC cells via modulating the Nrf2/HO-1 pathway.

Trace elements in outdoor and indoor PM2.5 in urban schools in Xi'an, Western China: characteristics, sources identification and health risk assessment.

The PM2.5-bounded elements were measured in outdoor and indoor from two urban middle schools in Xi'an. The PM2.5 mass was from 42.4 to 283.7 µg/m3 with bounded element from 3.4 to 41.7 µg/m3. Both the particle mass and the bounded elements displayed higher levels compared with previous studies in school environments. The most abundant elements were Ca, K, Fe, S, Zn and Cl both indoor and outdoor in two schools, which accounted for about 90% of the total elements. Strong correlations between indoor and outdoor were obtained along with relative effect from students' and teachers' activities on the indoor distributions between workdays and weekends. There had different indoor/outdoor (I/O) distributions for the two schools. It revealed the main outdoor sources for elements in JT and predominance of indoor sources in HT. The principal component analysis investigated main sources of elements in this study were coal combustion, geogenic dust and industrial emission, even though there displayed differences in the two school classrooms. The health risk assessment showed that the cancer risk for Ni and Pb was below the safe value while As and Cr might pose acceptable potential threat to both students' and teachers' health. The total non-cancer risks of accumulative multi-metals in JT exhibited to be higher than 1, indicating that there existed the potential non-carcinogenic health risks of exposure metals.

Optically-generated focused ultrasound for noninvasive brain stimulation with ultrahigh precision.

High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited precision at the millimeter level. Here, we report optically-generated focused ultrasound (OFUS) for non-invasive brain stimulation with ultrahigh precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with an ultrahigh lateral resolution of 83 µm, which is two orders of magnitude smaller than that of conventional transcranial-focused ultrasound (tFUS). Here, we show effective OFUS neurostimulation in vitro with a single ultrasound cycle. We demonstrate submillimeter transcranial stimulation of the mouse motor cortex in vivo. An acoustic energy of 0.6 mJ/cm2, four orders of magnitude less than that of tFUS, is sufficient for successful OFUS neurostimulation. OFUS offers new capabilities for neuroscience studies and disease treatments by delivering a focus with ultrahigh precision non-invasively.

High-precision neural stimulation by a highly efficient candle soot fiber optoacoustic emitter.

Highly precise neuromodulation with a high efficacy poses great importance in neuroscience. Here we developed a candle soot fiber optoacoustic emitter (CSFOE), capable of generating a high pressure of over 10 MPa with a central frequency of 12.8 MHz, enabling highly efficient neuromodulation in vitro. The design of the fiber optoacoustic emitter, including the choice of the material and the thickness of the layered structure, was optimized in both simulations and experiments. The optoacoustic conversion efficiency of the optimized CSFOE was found to be 10 times higher than the other carbon-based fiber optoacoustic emitters. Driven by a single laser, the CSFOE can perform dual-site optoacoustic activation of neurons, confirmed by calcium (Ca2+) imaging. Our work opens potential avenues for more complex and programmed control in neural circuits using a simple design for multisite neuromodulation in vivo.

Structural evolution and electronic properties of pure and semiconductor atom doped in clusters: Inn - , Inn Si- , and Inn Ge- (n = 3-16).

The bonding and electronic properties of Inn - , Inn Si- , and Inn Ge- (n = 3-16) clusters have been computationally investigated. An intensive global search for the ground-state structures of these clusters were conducted using the genetic algorithm coupled with density functional theory (DFT). The ground-state structures of these clusters have been identified through the comparison between simulated photoelectron spectra (PES) of the found lowest-energy isomers and the experimentally measured ones. Doping semiconductor atom (Si or Ge) can significantly change the structures of the In clusters in most sizes, and the dopant prefers to be surrounded by In atoms. There are three structural motifs for Inn X- (X = Si, Ge, n = 3-16), and the transition occurs at sizes n = 5 and 13. All Inn Si- and Inn Ge- share the same configurations and similar electronic properties except for n = 8. Among all above studied clusters, In13 - stands out with the largest vertical detachment energy (VDE), HOMO-LUMO gap, (Eb ) and second order energy difference Δ2 E due to its closed electronic shell of (1S)2 (1P)6 (1D)10 (2S)2 (1F)14 (2P)6 . Similarly, the neutral In12 X (X = Si, Ge) clusters are also identified as superatoms but with electronic configuration of (1S)2 (1P)6 (2S)2 (1D)10 (1F)14 (2P)6 .

Constructing 2D/2D ultrathin Ti3C2/SnS2 Schottky heterojunctions toward efficient tetracycline degradation.

In this article, a novel 2D/2D ultrathin Ti3C2/SnS2 Schottky heterojunctions have been prepared via a facile hydrothermal process. The properties of the heterojunction were fully characterized. The photocatalytic degradation performance of composites was examined by photo-degradation of tetracycline hydrochloride (TC-HCL) under visible light irradiation. Compared with single SnS2, 3% Ti3C2/SnS2 displayed the better performance, the removal rate of TC-HCL reached 87.7% and the kinetic rate constant (k) of the optimal 3% Ti3C2/SnS2 composite was about 2.7 times of that of bare SnS2. The improved photocatalytic activity of Ti3C2/SnS2 is ascribed to the formation of 2D/2D Schottky heterojunction, which promotes the spatial charge separation and increases the surface reactive sites.

Assessment of the inhalation exposure and incremental lifetime cancer risk of PM2.5 bounded polycyclic aromatic hydrocarbons (PAHs) by different toxic equivalent factors and occupancy probability, in the case of Xi'an.

Polycyclic aromatic hydrocarbons (PAHs) are widespread toxic pollutants in the atmosphere and have attracted much attention for decades. In this study, we compared the health risks of PAHs based on different toxic equivalent factors (TEFs) in a heavily polluted area during heating and non-heating periods. We also pay attention to occupancy probability (OP) in different polluted areas. The results showed that there were big differences for calculations by different TEFs, and also by OP or not. Age groups except adults were all lower calculated by OP than not. The sensitivity analysis results on the incremental lifetime cancer risks (ILCR) for population groups by Monte Carlo simulation identified that the cancer slope factor extremely affected the health risk assessment in heating periods, followed by daily inhalation exposure levels. However, daily inhalation exposure levels have dominated the effect on the inhalation ILCR and then followed by the cancer slope factor in non-heating periods. The big differences by different calculations investigated that it is important to set up the correlations between the pollution level and health risks, especially for the longtime health assessment.

The seasonal variation, characteristics and secondary generation of PM2.5 in Xi'an, China, especially during pollution events.

As an important central city in western China, Xi'an has the worst atmospheric pollution record in China and many measures have been taken to improve the air quality in the past few years. In this study, PM2.5 samples were collected across four seasons from 2017 to 2018 in Xi'an. Organic carbon and elemental carbon, water soluble ions, and elements were monitored to assess the air quality. The average annual PM2.5 concentration was (134.9 ± 48.1 µg/m3), with the highest concentration in winter (188.8 ± 93.2 µg/m3), and lowest concentration in summer (71.2 ± 12.1 µg/m3). The secondary generation of sulfate (SO42-) and nitrate (NO3-) was strong in spring, and secondary organic carbon (SOC) was formed in all seasons. The compositions of PM2.5 changed greatly during a sandstorm occurred and the Spring Festival. The sandstorm played a positive role in removing local pollutant NO3-, but also increased the concentration of SO42-, however both the concentration of SO42- and NO3- greatly increased by secondary generation during Spring Festival. Potential source analysis showed that during the sandstorm, pollutants were transported over a long distance from the northwest of China, whereas it was mainly from the local and surrounded emissions during the Spring Festival. Except Ca2+ and geological dust (GM), the other components in PM2.5 increased significantly on the day of the Spring Festival. During sampling time in Xi'an, the positive matrix factorization (PMF) model analysis showed that PM2.5 mainly came from vehicle emission, coal combustion, and biomass burning.

Stability Performance Analysis of Various Packaging Materials and Coating Strategies for Chronic Neural Implants under Accelerated, Reactive Aging Tests.

Reliable packaging for implantable neural prosthetic devices in body fluids is a long-standing challenge for devices' chronic applications. This work studied the stability of Parylene C (PA), SiO2, and Si3N4 packages and coating strategies on tungsten wires using accelerated, reactive aging tests in three solutions: pH 7.4 phosphate-buffered saline (PBS), PBS + 30 mM H2O2, and PBS + 150 mM H2O2. Different combinations of coating thicknesses and deposition methods were studied at various testing temperatures. Analysis of the preliminary data shows that the pinholes/defects, cracks, and interface delamination are the main attributes of metal erosion and degradation in reactive aging solutions. Failure at the interface of package and metal is the dominating factor in the wire samples with open tips.

A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective and Sensitive Detection of H2S: Synthesis, Spectra and Bioimaging.

Hydrogen sulfide (H2S) is an important signalling molecule with multiple biological functions. The reported H2S fluorescent probes are majorly based on redox or nucleophilic reactions. The combination usage of both redox and nucleophilic reactions could improve the probe's selectivity, sensitivity and stability. Herein we report a new dual-reactable probe with yellow turn-on fluorescence for H2S detection. The sensing mechanism of the dual-reactable probe was based on thiolysis of NBD (7-nitro-1,2,3-benzoxadiazole) amine (a nucleophilic reaction) and reduction of azide to amine (a redox reaction). Compared with its corresponding single-reactable probes, the dual-reactable probe has higher selectivity and fluorescence turn-on fold with magnitude of multiplication from that of each single-reactable probe. The highly selective and sensitive properties enabled the dual-reactable probe as a useful tool for efficiently sensing H2S in aqueous buffer and in living cells.

Dual-Reactable Fluorescent Probes for Highly Selective and Sensitive Detection of Biological H2 S.

Hydrogen sulfide (H2 S) is an important endogenous signaling molecule with a variety of biological functions. Development of fluorescent probes for highly selective and sensitive detection of H2 S is necessary. We show here that dual-reactable fluorescent H2 S probes could react with higher selectivity than single-reactable probes. One of the dual-reactable probes gives more than 4000-fold turn-on response when reacting with H2 S, the largest response among fluorescent H2 S probes reported thus far. In addition, the probe could be used for high-throughput enzymatic assays and for the detection of Cys-induced H2 S in cells and in zebrafish. These dual-reactable probes hold potential for highly selective and sensitive detection of H2 S in biological systems.

Fast-Response Turn-on Fluorescent Probes Based on Thiolysis of NBD Amine for H2 S Bioimaging.

Hydrogen sulfide (H2 S) is an important endogenous signaling molecule with multiple biological functions. New selective fluorescent turn-on probes based on fast thiolyling of NBD (7-nitro-1,2,3-benzoxadiazole) amine were explored for sensing H2 S in aqueous buffer and in living cells. The syntheses of both probes are simple and quite straightforward. The probes are highly sensitive and selective toward H2 S over other biologically relevant species. The fluorescein-NBD-based probe showed 65-fold green fluorescent increase upon H2 S activation. The rhodamine-NBD-based probe reacted rapidly with H2 S (t1/2 ≈1 min) to give a 4.5-fold increase in red fluorescence. Moreover, both probes were successfully used for monitoring H2 S in living cells and in mice. Based on such probe-based tools, we could observe H2 O2 -induced H2 S biogenesis in a concentration-dependent and time-dependent fashion in living cells.

Branch-PCR Constructed Stable shRNA Transcription Nanoparticles Have Long-Lasting RNAi Effect.

RNA interference (RNAi) is a cellular process for gene silencing. Because of poor serum stability, transferring dsRNA directly into the target cells is a challenge. We report a facile and universal strategy to construct short hairpin RNA (shRNA) transcription nanoparticles with multiple shRNA transcription templates by PCR with flexible branched primers (branch-PCR). Compared with conventional linear shRNA transcription templates, these shRNA transcription nanoparticles show excellent stability against digestion by exonuclease III. Importantly, we found that our highly stable shRNA transcription nanoparticles can also be transcribed and thus induce efficient and long-lasting RNAi with picomolar activity in living mammalian cells. These chemically well-defined branch-PCR-generated stable shRNA transcription nanoparticles might facilitate RNAi delivery with a long-lasting RNAi effects.