By issuing earnings forecasts for both current and future years simultaneously, managers provide the multiyear data needed for more accurate valuations and help investors sort out transitory and permanent shocks. We examine whether and how firms' issuance of multiyear earnings forecasts mitigates equity mispricing. We find that growing, better- performing, and high litigation-risk firms, and firms that missed their guidance issue more multiyear forecasts, whereas firms facing greater forecasting difficulty issue fewer. After firms issue multiyear forecasts, mispricing tends to be corrected, especially when underpriced firms issue both long- and short-term good news forecasts and when overpriced firms issue long-term bad news forecasts. The delayed response to earnings (i.e., PEAD) decreases when firms issue multiyear forecasts. Analysts' 12-month-ahead price forecasts become more accurate when multiyear earnings forecasts are issued, suggesting that more accurate analyst valuation is one channel through which equity mispricing is corrected. Lastly, we find that the current-period earnings-return relation becomes more linear when firms issue multiyear earnings forecasts, which suggests that investors underreact less to extreme news because the future years' forecasts embed earnings persistence data. However, the greater linearity may reflect the higher earnings persistence of firms self-selecting to issue multiyear earnings forecasts.

The Golgi apparatus (GA), a critical sub-cellular organelle, plays a pivotal role in numerous biological signaling pathways, including the post-translational modification of proteins and their secretion to various cellular destinations. Dysregulation of GA function is implicated in the development of several diseases, including cancer. As a result, detouring clinically approved drugs into the GA for an enhanced anti-cancer effect remained a major challenge. To address this, herein, we designed and synthesized NSAID-based conjugates incorporating a fluorophore (1,8-naphthalimide) and a Golgi-homing moiety (phenylsulfonamide). Screening these conjugates in cervical (HeLa) and colon (HCT-116) cancer cells identified a particularly promising candidate: the ibuprofen-1,8-naphthalimide-phenylsulfonamide conjugate (7a) which exhibited significant cytotoxicity against HCT-116 cells as well as in lung cancer (A549), colon carcinoma (Caco-2) and breast cancer (MCF7) cells. Interestingly, compound 7a self-assembled into nanoscale petal-like structures in water and efficiently homed into the GA as well as in the endoplasmic reticulum (ER) within 30 min to induce morphological damage to the GA. Compound 7a mediated GA damage increased the expression of Beclin and LC3-I/II proteins to induce autophagy which was further inhibited by chloroquine (CQ) and bafilomycin A1 (BFA) leading to remarkable HCT-116 cell death in combination with 7a. Moreover, compound 7a triggered apoptosis by downregulating anti-apoptotic Bcl-2 and Cas-3 as well as cleaving PARP proteins in HCT-116 cells, while demonstrating no toxicity towards non-cancerous human retinal pigment epithelial cells (RPE-1). Interestingly, compound 7a also reduced the size and growth of the HeLa 3D spheroids significantly after 72 h. This ibuprofen derivative (7a) holds promise as a valuable tool for illuminating the chemical biology of the GA in cancer cells and as a potential candidate for anti-cancer therapy.

We study how nonfinancial firms' operating risks change after bank competition increases. By exploiting the 1990s staggered regulatory reforms across U.S. states that allowed interstate banking and branching, we show that out-of-state bank entry was associated with lower borrower risk-taking on average. Large, profitable, safe, and geographically diversified firms signed up as new clients of large entrant banks, which offered larger and cheaper loans that reflected their higher efficiency and risk reduction through geographical diversification. We argue that these large banks could substitute for local relationship lending with more data collection from branches in multiple states. Firms that began borrowing from entrant banks increased capital expenditures and project-specific financing and kept R&D expenses stable but reduced R&D risk. Firms that continued borrowing from incumbent banks paid higher interest rates and increased their risk, suggesting that their credit access fell. States that opened up more had bigger changes in these outcomes.

We examine how much consumer product recalls damage corporate reputation and whether firms can mitigate such damage by strategically timing their recall announcements. We use sales changes, tangible asset impairments, employee reviews, and analysts' sales growth forecasts and stock recommendations as proxies for a firm's external and internal reputation. We document statistically and economically significant reputational damage from product recalls across multiple stakeholders. This damage helps explain the negative stock price reactions to product recalls. We show that firms strategically time their recall announcements to avoid media attention, especially when dealing with a large recall in a competitive industry with limited product differentiation. Such strategic timing helps mitigate the reputational damage for small, less visible firms but does not benefit large firms.

Cancer remains as one of the most life-threatening diseases in the whole world. Most of the therapeutic strategies to eradicate cancer are highly invasive, leading to severe injury and trauma to the patients. In recent times, phototherapy has emerged as one of the noninvasive therapeutic strategies for cancer treatment. However, development of novel small-molecule photothermal agents remains a major challenge. To address this, herein, a small molecule library having aromatic substituted-3-methoxy-pyrrole and 2-(3-cyano-4,5,5-trimethylfuran-2(5 H)-ylidene) malononitrile in a concise synthetic strategy is designed and synthesized. One of the library members (7H) self-assembles into spherical-like nanoparticles having <100 nm size in water and is found to exhibit remarkable increase in temperature under 740 nm near-infrared (NIR) light. Interestingly, compound 7H homes into the lysosomal compartments and the lipid droplets in the HCT-116 colon cancer cells within 3 h and induces photothermal effect followed by generation of reactive oxygen species while irradiating under 740 nm NIR light for 10 min. Moreover, 7H triggers programmed cell death (apoptosis) to induce remarkable HCT-116 cell killing. This small molecule-mediated photothermal effect shows potential to be an interesting tool for the next-generation noninvasive cancer phototherapy.

From a synthetic endoplasmic reticulum (ER)-targeted NSAID library, an ibuprofen derivative was identified to induce ER stress followed by autophagy to trigger apoptosis in HCT-116 colon cancer cells.

Cancer is the second leading cause of death globally, which can be treated through invasive chemotherapeutic strategies, leading to severe toxic side effects, injury, and trauma to the patients. Recently, phototherapy gained lots of attention as an alternative, non-invasive cancer therapy. However, developing novel small molecules as chemophototherapeutic agents remained a major challenge. To address this, herein, we have designed and synthesized a small molecule library consisting of aromatic moieties as π-donor, 3-methoxy-pyrrole as π-electron-rich pharmacophore, and cyanine or N-methyl-quinolinium ion as π-acceptor in a concise strategy. Upon screening in colon (HCT-116), cervical (HeLa), and lung (A549) cancer cells, one small molecule (6a) was identified to induce remarkable HCT-116 cell killing under 740 nm LED irradiation by generating a diverse array of reactive oxygen species (ROS) and showing negligible toxicity toward non-cancerous, kidney fibroblast-like Cos-7 cells. Interestingly, compound 6a self-assembled into spherical nanoparticles that homed into the lysosomal compartment of HCT-116 cells efficiently within 3 h, impaired the lysosomal membrane, followed by induction of autophagy and generation of ROS to trigger late apoptosis and necrosis with increased penetration efficiency in 3D-HeLa spheroids under light irradiation. Compound 6a can be a tool for the development of a novel chemo-photodynamic probe for cancer therapy.

The Golgi apparatus (GA) is one of the most important subcellular organelles controlling protein processing, post-translational modification and secretion. Dysregulation of the GA structure and function leads to multiple pathological states, including cancer development and metastasis. Consequently, visualizing GA dynamic structures and their impairment in cancer has emerged as a novel strategy for next-generation unorthodox cancer therapeutics. However, the major challenge in GA-mediated theranostic probe development is the specific targeting of the GA within the subcellular milieu due to the lack of GA-recognizing chemical entities. In this review, we delineated various chemical functionalities that are extensively used as GA-homing moieties. Moreover, we outlined GA imaging probes consisting of classical fluorophores as well as novel aggregation-induced emissive (AIE) probes tagged with GA-homing moieties. Furthermore, we described GA-impairing molecules that can damage GA morphology through chemotherapeutic and photodynamic therapy (PDT) in cancer. Finally, we addressed the current challenges in this emerging and underexplored field of GA-targeted theranostics and proposed potential solutions to guide future cancer therapeutics.

We compare how sustainability-linked loans issued by U.S. and European borrowers change valuations around a major amendment to global sustainability-contracting guidelines. Loose U.S. federal regulations help us disentangle the effects of public and private interventions in sustainability performance. This private amendment increased the value of U.S. sustainability-linked loans over conventional loans, while European sustainability-linked loans were not affected by the amendment. Further, while both European and U.S. sustainability-linked loan issuers reduce carbon emissions after the private amendment, only U.S. borrowers do so without eroding financial performance. The amendment effect is stronger for U.S. firms without strict state climate rules and for those without European subsidiaries. Our findings highlight that private rule-setting can facilitate customized value-enhancing sustainability efforts that one-size-fits-all public regulations may not.

Mitochondrion has appeared as one of the important targets for anti-cancer therapy. Subsequently, small molecule anti-cancer drugs are directed to the mitochondria for improved therapeutic efficacy. However, simultaneous imaging and impairing mitochondria by a single probe remained a major challenge. To address this, herein Chimeric Small Molecules (CSMs) encompassing drugs, fluorophore and mitochondria homing moiety were designed and synthesized through a concise strategy. Screening of the CSMs in a panel of cancer cell lines (HeLa, MCF7, A549, and HCT-116) revealed that one of the CSMs comprising Indomethacin V exhibited remarkable cervical cancer cell (HeLa) killing (IC50=0.97 mu M). This lead CSM homed into the mitochondria of HeLa cells within 1 h followed by mitochondrial damage and reactive oxygen species (ROS) generation. This novel Indomethacin V-based CSM-mediated mitochondrial damage induced programmed cell death (apoptosis). We anticipate these CSMs can be used as tools to understand the drug effects in organelle chemical biology in diseased states. Chimeric Small Molecules (CSMs) were designed and synthesized in a concise strategy. One of the CSMs localized into the mitochondria, damaged them and generated ROS, leading to remarkable cancer cell killing in different cancer cell lines. These CSMs can be useful tools to understand organelle chemical biology in diseased states.image

Herein, we have designed and synthesised a 2,6-dihydroxybenzoyl-hydrazone (compound 3) fluorophore through a concise strategy. Molecular dynamics and quantum mechanical simulations revealed that long range charge transfer (CT) to be the underlying mechanism for the emissive property of compound 3. Confocal microscopy and cell viability assays confirmed that within 3 h, compound 3 homed into the Golgi-apparatus of colon cancer cells (HCT-116) selectively compared to the breast (MCF7), lung (A549), cervical (HeLa) cancer cells and non-cancerous retinal epithelial pigment cells (RPE-1) with negligible toxicity. This novel fluorophore has potential to image Golgi-apparatus in a cancer cell specific manner for diagnosis.

In recent years, impairing mitochondria in cancer cells gained attention as alternative cancer therapy. In this context, non-steroidal anti-inflammatory (NSAID) drugs are interesting candidates to damage mitochondria in cancer cells. However, routing NSAIDs specifically into the mitochondria remained a major challenge and less explored. Herein, we have synthesized a small library of Meclofenamic acid and Naproxen derivatives having ester and amide linkage with substituted triphenylphosphonium cations for mitochondria targeting. Screening in cervical cancer (HeLa), breast cancer (MCF7) and colon cancer (HCT-116) cells revealed a Meclofenamic acid derivative having ester linkage with tri (4-methoxyphenyl) phosphonium cation (8A3) which induced mitochondrial damage through mitochondrial outer membrane permeabilization (MOMP) followed by generation of reactive oxygen species (ROS) in the HCT-116 cells. This 8A3-mediated mitochondrial impairment triggered apoptosis by inhibiting Cox-2, reduction in Bcl-2/Bcl-xl expression and Caspase-3/9 cleavage leading to remarkable HCT-116 cell death. This novel mitochondrion targeted Meclofenamic acid derivative has the potential to be used as a chemical biology tool to understand the role of NSAIDs in mitochondria towards cancer therapy.

Lung cancer remains a lethal disease globally. Recently, the development and progression of lung cancer were strongly linked with mitochondrial dysfunction. Hence, targeting mitochondria in lung cancer can be an interesting alternative strategy for therapeutic applications. To address this, we have designed and synthesized a 3-methoxy-pyrrole-enamine-triphenylphosphonium cation-based library through a concise chemical strategy. Upon screening this library in cervical (HeLa), colon (HCT-116), breast (MCF7), and lung (A549) cancer cells, we identified a small molecule that self-assembled into nanoscale spherical particles with a positive surface charge. This nanoparticle was confined to the mitochondria to induce mitochondrial damage and produced reactive superoxide in A549 cells. This small molecule self-assembled nanoparticle-mediated mitochondrial damage triggered apoptosis leading to the remarkable killing of A549 cells. These 3-methoxy-pyrrole-enamine-triphenylphosphonium nanoparticles can be used as a tool to understand the chemical biology of mitochondria in lung cancer for chemotherapeutic applications.

The endoplasmic reticulum plays an important role in maintaining the protein homeostasis of cells as well as regulating Ca2+ storage. An increased load of unfolded proteins in the endoplasmic reticulum due to alterations in the cell's metabolic pathway leads to the activation of the unfolded protein response, also known as ER stress. ER stress plays a major role in maintaining the growth and survival of various cancer cells, but persistent ER stress can also lead to cell death and hence can be a therapeutic pathway in the treatment of cancer. In this review, we focus on different types of small molecules that impair different ER stress sensors, the protein degradation machinery, and chaperone proteins. We also review the metal complexes and other miscellaneous compounds inducing ER stress through multiple mechanisms. Finally, we discuss the challenges in this emerging area of research and the potential direction of research to overcome them towards next-generation ER-targeted cancer therapy.

Endoplasmic reticulum (ER) is one of the most important sub-cellular organelles which controls myriads of biological functions including protein biosynthesis with proper functional folded form, protein misfolding, protein transport into Golgi body for secretion, Ca2+ homeostasis and so on. Subsequently, dysregulation in ER function leads to ER stress followed by disease pathology like cancer. Hence, targeting ER in the cancer cells emerged as one of the futuristic strategies for cancer treatment. However, the major challenge is to selectively and specifically target ER in the sub-cellular milieu in the cancer tissues, due to the lack of ER targeting chemical moieties to recognize the ER markers. To address this, in the last decade, numerous biomaterials were explored to selectively impair and image ER in cancer cells to induce ER stress. This review outlines those biomaterials which consists of carbon and silicon materials, lipid nanoparticles (liposomes and micelles), supramolecular self-assembled nanostructures, cell membrane-coated nanoparticles and metallic nanoparticles. Moreover, we also discuss the challenges and possible solutions of this promising field to usher the readers towards next-generation ER targeted cancer therapy.

Researchers often use regression-based x-Scores (e.g., conservatism C-Score, misstatement F-Score) from a stage 1 model as a dependent variable in stage 2. We argue that this x-Score analysis can cause coefficient biases and interpretation problems because (1) x-Score does not capture new sources of variation, and (2) the estimates often hinge on unacknowledged technical assumptions. Instead, we recommend that researchers include the test variables and the relevant controls in stage 1, obviating the need for an x-Score. In replication analyses, some important published findings change after we remove the coefficient bias caused by the use of x-Score as a dependent variable.